A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Lupus: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83626-4 1. Lupus-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on lupus. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON LUPUS........................................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Lupus .......................................................................................... 15 E-Journals: PubMed Central ..................................................................................................... 114 The National Library of Medicine: PubMed .............................................................................. 118 CHAPTER 2. NUTRITION AND LUPUS ............................................................................................ 253 Overview.................................................................................................................................... 253 Finding Nutrition Studies on Lupus ......................................................................................... 253 Federal Resources on Nutrition ................................................................................................. 262 Additional Web Resources ......................................................................................................... 262 CHAPTER 3. ALTERNATIVE MEDICINE AND LUPUS ..................................................................... 265 Overview.................................................................................................................................... 265 National Center for Complementary and Alternative Medicine................................................ 265 Additional Web Resources ......................................................................................................... 284 General References ..................................................................................................................... 288 CHAPTER 4. DISSERTATIONS ON LUPUS ....................................................................................... 289 Overview.................................................................................................................................... 289 Dissertations on Lupus .............................................................................................................. 289 Keeping Current ........................................................................................................................ 292 CHAPTER 5. CLINICAL TRIALS AND LUPUS .................................................................................. 293 Overview.................................................................................................................................... 293 Recent Trials on Lupus .............................................................................................................. 293 Keeping Current on Clinical Trials ........................................................................................... 313 CHAPTER 6. PATENTS ON LUPUS .................................................................................................. 315 Overview.................................................................................................................................... 315 Patents on Lupus ....................................................................................................................... 315 Patent Applications on Lupus ................................................................................................... 339 Keeping Current ........................................................................................................................ 347 CHAPTER 7. BOOKS ON LUPUS ...................................................................................................... 349 Overview.................................................................................................................................... 349 Book Summaries: Federal Agencies............................................................................................ 349 Book Summaries: Online Booksellers......................................................................................... 354 The National Library of Medicine Book Index ........................................................................... 360 Chapters on Lupus ..................................................................................................................... 361 Directories.................................................................................................................................. 363 CHAPTER 8. MULTIMEDIA ON LUPUS ........................................................................................... 365 Overview.................................................................................................................................... 365 Video Recordings ....................................................................................................................... 365 Bibliography: Multimedia on Lupus.......................................................................................... 366 CHAPTER 9. PERIODICALS AND NEWS ON LUPUS ........................................................................ 369 Overview.................................................................................................................................... 369 News Services and Press Releases.............................................................................................. 369 Newsletters on Lupus ................................................................................................................ 374 Newsletter Articles .................................................................................................................... 374 Academic Periodicals covering Lupus........................................................................................ 380 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 381 Overview.................................................................................................................................... 381 U.S. Pharmacopeia..................................................................................................................... 381 Commercial Databases ............................................................................................................... 382
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Researching Orphan Drugs ....................................................................................................... 383 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 387 Overview.................................................................................................................................... 387 NIH Guidelines.......................................................................................................................... 387 NIH Databases........................................................................................................................... 389 Other Commercial Databases..................................................................................................... 392 The Genome Project and Lupus ................................................................................................. 392 APPENDIX B. PATIENT RESOURCES ............................................................................................... 397 Overview.................................................................................................................................... 397 Patient Guideline Sources.......................................................................................................... 397 Associations and Lupus ............................................................................................................. 411 Finding Associations.................................................................................................................. 415 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 417 Overview.................................................................................................................................... 417 Preparation................................................................................................................................. 417 Finding a Local Medical Library................................................................................................ 417 Medical Libraries in the U.S. and Canada ................................................................................. 417 ONLINE GLOSSARIES................................................................................................................ 423 Online Dictionary Directories ................................................................................................... 426 LUPUS DICTIONARY.................................................................................................................. 429 INDEX .............................................................................................................................................. 537
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with lupus is indexed in search engines, such as www.google.com or others, a nonsystematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about lupus, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to lupus, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on lupus. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to lupus, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on lupus. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON LUPUS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on lupus.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and lupus, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “lupus” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Prevalence of Infective Endocarditis in Patients with Systemic Lupus Erythematosus Source: JADA. Journal of the American Dental Association. 130(3): 387-392. March 1999. Summary: Compared with the general population, patients with systemic lupus erythematosus (SLE) have an increased prevalence of functionally impaired cardiac valves due to the presence of Libman Sacks lesions. These lesions may place patients with SLE at risk of developing infective endocarditis (IE). This article reports on a study that featured a retrospective chart review undertaken to determine the association between SLE with valvulopathy and IE. The authors reviewed the records of 361 patients from two health care facilities who had the diagnostic code of SLE. Of the 275 records that met the 1982 revised American Rheumatism Association criteria for SLE, 51 (18.5 percent) were for patients who had a clinically detectable heart murmur that resulted in echocardiography being performed. Nine (3.3 percent) of the 275 patients
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had a clinically significant valvular abnormality, three (1.1 percent) had a potentially significant valvular abnormality, and one (0.4 percent) had a history of IE that was diagnosed two years before her diagnosis of SLE was made. The findings suggest that 18.5 percent of this group of patients with SLE had a clinically detectable heart murmur that would require further investigation to determine its significance. Furthermore, between 3.3 and 4.4 percent of the study population had cardiac valve abnormalities that potentially required antibiotic prophylaxis before certain dental procedures. However, the authors identified no cases that demonstrated an association between IE and diagnosed SLE. The authors conclude that dentists should query their patients with SLE about their cardiac status and consult with the patient's physician if the cardiac status is unknown. Patients with confirmed valvular abnormalities should receive antibiotic prophylaxis for designated bacteremia producing dental procedures. 1 table. 55 references. (AA). •
Systemic Lupus Erythematosus: Recognizing its Various Presentations Source: Postgraduate Medicine. 97(4): 79, 83, 86, 89-90, 92-94. April 1995. Contact: Available from McGraw-Hill, Inc. 1221 Avenue of the Americas, New York, NY 10020. (612) 832-7869. Summary: In this article, the author discusses the epidemiologic and pathogenetic factors of systemic lupus erythematosus (SLE) and describes the many manifestations of the disease. Symptoms discussed include skin signs, musculoskeletal manifestations, cardiovascular involvement, renal findings, pulmonary features, gastrointestinal symptoms, neuropsychiatric disease, hematologic features, immunologic factors, and systemic manifestations. The author discusses probably causative factors, including genetic predisposition, complement deficiencies, persistence of antigen, drugs, and environmental factors. The author also presents a brief overview of current treatment options for SLE. 3 figures. 1 table. 19 references.
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Shedding New Light on Lupus Source: American Journal of Nursing. 94(11): 26-32. November 1994. Contact: Available from AJN Subscription Department. P.O. Box 50480, Boulder, CO 80322-0480. (800) 627-0484 or (303) 447-9330. Summary: In this article, the authors bring nurses up to date on systemic lupus erythematosus (SLE) and its management. Topics include a description of the disease and how it affects the body; the wide variety in course and presentation of the disease; the criteria for classifying lupus; childbearing and contraception for women with SLE; treatment options, including medications, rest, exercise, proper nutrition, and stress management; teaching patients about medications; counseling patients about stress; and the role of family and other support groups. Readers can qualify for continuing education credits with the posttest at the end of the article. 1 figure. 1 table. 9 references.
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Lupus Erythematosus: Considerations for Dentistry Source: JADA. Journal of American Dental Association. 129(3): 330-339. March 1998. Summary: Lupus erythematosus (LE) is a connective tissue disease that affects a number of organ systems. Patients with this condition can experience several other serious conditions, including bleeding, infection, endocarditis, adrenal insufficiency, and mucocutaneous disease; these conditions can affect the provision of dental care. In this article, the authors describe considerations for managing dental treatment in patients
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with LE. Topics include pathogenesis of LE, different forms of LE, diagnosis and laboratory evaluation of the disease, clinical manifestations, and dental management considerations for each of the complications of LE. The authors emphasize that, before undertaking the dental care of a patient with LE, a dentist must consider the patient's immunosuppressed status, as well as the risks of adrenal insufficiency, hematologic disease, renal insufficiency and endocarditis; then, the dentist must diagnose and manage the various oral and dental manifestations of the disease. One sidebar summarizes recommendations for pre-dental care, during care, and post dental care for the treatment of patients with LE. 2 figures. 3 tables. 54 references. (AA-M). •
Progress in the Treatment of Proliferative Lupus Nephritis Source: Current Opinion in Nephrology and Hypertension. 9(2): 107-115. 2000. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-2400. Website: www.currentopinion.com. Summary: Lupus nephritis (kidney inflammation associated with systemic lupus erythematosus, or SLE) is often well developed at the time of diagnosis. This article reviews progress in the treatment of proliferative lupus nephritis. High dose corticosteroids are universally accepted as the initial approach to the control of severe inflammation in the kidney. Long term disease control and the minimization of iatrogenic (physician caused) risk usually require adjunctive therapies that target the more fundamental immunoregulatory disturbances of lymphoid cells. Of the available cytotoxic drugs, cyclophosphamide is currently among the most effective, although it cannot be considered ideal in terms of efficacy or toxicity. New prospects for the treatment of proliferative lupus nephritis include novel immunosuppressive agents (e.g., mycophenolate, cyclosporine, fludarabine), combination chemotherapy (e.g., cyclophosphamide plus fludarabine), and sequential chemotherapy (e.g., cyclophosphamide followed by azathioprine), immunological reconstitution using intensive cytoreductive chemotherapy (with or without stem cell rescue), and co stimulatory molecule inhibition. Gene therapy remains an attractive prospect, but its feasibility clearly depends on the further definition of lupus promoting genes and the availability of methods to establish stable expression of disease corrective genes in the appropriate lymphoid cells. 3 figures. 83 references.
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Treatment of Lupus Nephritis Source: Seminars in Nephrology. 20(3): 265-276. May 2000. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: Patients with lupus nephritis pose a therapeutic challenge and stimulate investigation of innovative treatment strategies. This article reviews those current and potential strategies that may optimize management of lupus nephritis. The clinical presentations of lupus nephritis can vary from asymptomatic hematuria (blood in the urine) or proteinuria (protein in the urine) to acute nephritic or nephrotic syndromes and from rapidly progressive glomerulonephritis to insidious chronic renal insufficiency. Although patient survival and renal function outcomes have improved over the last 4 decades, contemporary immunosuppressive regimens are not consistently effective and often require extended courses (resulting in negative drug effects and toxicity). Several strategies are under investigation to induce remissions more rapidly and to reduce the risk of long courses of cytotoxic drug therapy. The
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combination of pulse methylprednisolone and pulse cyclophosphamide may be more effective than pulse cyclophosphamide alone for patients with relatively severe proliferative lupus nephritis. A particularly vigorous strategy employs immunoablative cyclophosphamide, with or without stem cell rescue. Several studies of sequential immunosuppressive therapy are in progress. It is anticipated that long term toxicities can be lessened by substituting various maintenance agents (e.g., azathioprine or mycophenolate mofetil) after initial cyclophosphamide therapy has induced a renal responses. Innovative approaches (e.g., costimulatory blockade) offer the hope of more effective treatments without the risks of contemporary regimens. 2 figures. 2 tables. 88 references. •
Natural History and Treatment of Lupus Nephritis Source: Seminars in Nephrology. 19(1): 2-11. January 1999. Contact: Available from W.B. Saunders Company. Periodicals Department. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Summary: Renal involvement occurs in most patients with systemic lupus erythematosus (SLE). This article discusses the natural history and treatment of lupus nephritis. Contemporary therapeutic regimens for immunosuppression and for the treatment of hypertension, hyperlipidemia, infections, and seizures have likely contributed to improvements in the prognosis of these patients over the past four decades. Corticosteroids usually ameliorate the manifestations of lupus nephritis but achieve less complete and sustained remissions than cytotoxic drugs. Among the cytotoxic drugs, pulse cyclophosphamide has one of the best profiles of efficacy and toxicity. Because each episode of lupus nephritis exacerbation results in cumulative scarring, atrophy, and fibrosis, the authors recommend continued maintenance treatment for 1 year beyond the point of complete remission of proliferative lupus nephritis. Studies are in progress to determine whether innovative treatment strategies will enhance efficacy and minimize toxicity associated with cytotoxic drug therapies. Lupus membranous nephropathy poses a lower risk of renal failure, but persistent nephrotic syndrome confers risks of cardiovascular events; this form of lupus nephritis is usually treated with less intensive regimens of corticosteroids, cytotoxic drugs, or cyclosporine. The prognosis and overall success of treatment for lupus nephritis seem to vary widely among geographically and racially diverse populations. The causes for the apparently worse prognosis and poorer responses to treatment of lupus nephritis in African American patients are currently unexplained and require further study. Until such data are available, caution is clearly warranted in extrapolating evidence, particularly about the prognosis and effects of treatment among different populations of patients with lupus nephritis. 4 figures. 2 tables. 85 references. (AA).
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Lower Urinary Tract Symptoms in Patients with Sjogren's Syndrome and Systemic Lupus Erythematosus Source: International Urogynecology Journal. 11(2): 84-86. 2000. Contact: Available from Springer-Verlag New York Inc. 175 Fifth Avenue, New York, NY 10010. (212) 460-1500. Fax (212) 473-6272. Summary: Sjogren's syndrome (SS) and systemic lupus erythematosus (SLE) are autoimmune diseases which have many similarities with interstitial cystitis (IC), a urinary bladder disease with unknown etiology. This article reports on a survey studying the occurrence, severity, and nature of lower urinary tract symptoms among patients with SS or SLE. The results showed that these patients have significantly more
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urinary complaints, especially irritative bladder symptoms, than age and sex matched controls. The authors studied 36 patients with SS, 85 patients with SLE, and 121 controls. In these groups, 25 percent, 29 percent, and 66 percent, respectively, were free of urinary symptoms. The prevalences of mild symptoms were 61 percent (SS), 62 percent (SLE), and 27 percent (control group); and severe symptoms 14 percent (SS), 9 percent (SLE), and 7 percent (control group). SS and SLE patients with urinary complaints reported mostly urinary frequency (27 percent of SS and 62 percent of SLE patients) and suprapubic pain (36 percent of SS and 34 percent of SLE patients). The most common symptom in the control group was stress urinary incontinence. The frequency of lower urinary tract problems in patients with SS and SLE supports the concept that autoimmune disorders also have bladder manifestations. 2 tables. 21 references. •
Advances in the Treatment of Lupus Nephritis Source: in Coggins, C.H. Hancock, E.W., Eds. Annual Review of Medicine: Selected Topics in the Clinical Sciences, Volume 45. Palo Alto, CA: Annual Reviews Inc. 2001. p. 63-78. Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax: (415) 855-9815. PRICE: $47. ISBN: 0824305450. Summary: Systemic lupus erythematosus (SLE) is an autoimmune disease that leads to the formation and deposition of immune complexes throughout the body, which are pathogenic (causing disease) for SLE. Different forms of glomerulonephritis (inflammation of the filtering units of the kidney) can occur in patients with SLE and can contribute significantly to the associated morbidity (illness and complications) and, ultimately, mortality (death) from the disease. Over the past two decades, there have been significant strides in the understanding of the disease and in treatments that attempt to control the formation and deposition of anti-DNA auto-antibodies and immune complexes, as well as the subsequent inflammatory cascade mediated through various cellular and humoral pathways leading to progressive renal (kidney) damage and end stage renal disease (ESRD). This article reviews the current understanding of the pathogenesis and treatment of lupus nephritis in its various stages and discusses the experimental and human data regarding some of the potential newer forms of therapy. The authors discuss data regarding the use of steroids, azathioprine, cyclophosphamide, cyclosporine A, mycophenolate mofetil, gammaglobulin, plasmapheresis, LJP 394, flaxseed oil, bindarit, anti-CD-40 ligand, and CRLA41g. The authors conclude that the long term morbidity and mortality for patients with lupus nephritis (LN) has improved markedly over the past two decades. This is due in part to the addition of newer adjunctive therapies to control blood pressure and intraglomerular pressure, reduce proteinuria (protein in the urine), and manage hyperlipidemia (high levels of fats in the blood). 89 references.
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Efficacy of Mycophenolate Mofetil in Patients with Diffuse Proliferative Lupus Nephritis Source: New England Journal of Medicine. 343(16): 1156-1162. October 19, 2000. Summary: The combination of cyclophosphamide and prednisolone is effective for the treatment of severe lupus nephritis (kidney inflammation associated with systemic lupus erythematosus or SLE) but has serious adverse effects. This article reports on a study that investigated the efficacy of mycophenolate mofetil in patients (n = 42) with proliferative lupus nephritis. The authors compared the efficacy and side effects of a regimen of prednisolone and mycophenolate mofetil given for 12 months (group 1) with
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those of a regimen of prednisolone and cyclophosphamide given for 6 months, followed by prednisolone and azathioprine for 6 months (group 2). Of the patients in Group 1 (n = 21), 81 percent had a complete remission, and 14 percent had a partial remission, as compared with 76 percent and 14 percent, respectively, of the 21 patients in Group 2. The improvements in the degree of proteinuria (protein in the urine) and the serum albumin (protein levels in the blood) and creatinine concentrations were similar in the two groups. One patient in each group discontinued treatment because of side effects. Infections were noted in 19 percent of the patients in Group 1 and in 33 percent of those in Group 2. Other adverse effects occurred only in group 2; they included amenorrhea (23 percent), hair loss (19 percent), leukopenia (10 percent), and death (10 percent). The rates of relapse were 15 percent in Group 1, and 11 percent in Group 2. The authors conclude that for the treatment of diffuse proliferative lupus nephritis, the combination of mycophenolate mofetil and prednisolone is as effective as a regimen of cyclophosphamide and prednisolone followed by azathioprine and prednisolone, with similar levels of toxicity. 2 figures. 4 tables. 15 references. •
Hepatitis-Lupus Connection Source: Seminars in Liver Disease. 11(3): 234-240. August 1991. Summary: This article investigates the connection between chronic active hepatitis (CAH) and systemic lupus erythematosus (SLE). Topics discussed include a definition of both conditions; a review of the literature; the pathologic aspects; the serologic aspects including DNA and nuclear antigens, smooth muscle antigens, atypical serologic reactivities in CAH, and the liver-kidney microsomal antigen; the immunogenetic aspects, including the HAL-B8-DR3 association, complement alleles, and the Gm allotype markers; and pathogenetic aspects. The author concludes that autoimmune hepatitis and SLE are diseases with some similar serologic expressions, as judged by formation of antinuclear antibodies (ANA), but the specificities of these ANAs differ. 66 references.
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Systematic Lupus Erythematosus: Dental Hygiene Management Source: Case Studies in Periodontal Management. 1(2): 1-4. August 1995. Summary: This article presents a case of a male patient with systemic lupus erythematosus (SLE), whose periodontal status was affected by several factors relating to the SLE. SLE is an autoimmune disease of unknown origin affecting the connective tissues and various organs in the body. The patient presented with severely decayed teeth and advanced periodontal disease. The oral health plan was developed in conjunction with the patient's physician, dental and dental hygiene faculty members, and a dental and dental hygiene student. Topics include the clinical features and oral manifestations of SLE; the medical and dental history of the case client; the diagnosis and treatment plan; the implementation phase, including patient education; evaluation of the dental hygiene treatment; complications to care; and modifications suggested for future care of this patient. 'Before' and 'after' pictures of the patient's teeth and gingiva are provided. 3 figures. 1 table.
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End-Stage Renal Disease and Systemic Lupus Erythematosus Source: American Journal of Medicine. 101(1): 100-107. July 1996. Summary: This article reports on a literature review to provide an overview of the course of systemic lupus erythematosus (SLE) following the onset of end-stage lupus nephropathy, regarding clinical and serological manifestations, survival on dialysis, and
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renal transplant outcomes. Results showed that there is a tendency for decreased clinical and serological lupus activity following the onset of end-stage renal disease (ESRD). Survival of lupus patients on dialysis is no different from that of non-SLE dialysis patients, and is better than that of several other rheumatic diseases. Following renal transplantation, there is no difference in patient or graft survival in lupus versus nonlupus patients. Like their nonlupus counterparts, SLE transplant patients do better with living relative grafts or regimens containing cyclosporin A or both. Transplantation during an acute exacerbation of SLE is controversial and may increase the risk of poor outcomes. 4 tables. 59 references. (AA-M). •
Reliability of Histologic Scoring for Lupus Nephritis: A Community-Based Evaluation Source: Annals of Internal Medicine. 119(8): 805-811. 1993. Summary: This article reports on a research study undertaken to determine the reliability of the National Institutes of Health (NIH)-modified semiquantitative histologic scoring system for lupus nephritis. Five pathologists, all experienced in reading renal biopsy specimens, assessed 25 specimens that had been obtained from patients with a clinical diagnosis of systemic lupus erythematosus and showed diffuse proliferative glomerulonephritis. Biopsy specimens were scored independently and blindly by pathologists for components of nephritis chronicity and activity. Reliability was measured by percentage agreement, intraclass correlation coefficient or kappa statistic, and individual reader effect on the group arithmetic mean. The results show that, in a nonreferral setting, the NIH-modified scoring system for lupus nephritis is only moderately reproducible. The authors stress that, if this system is used to predict renal outcome, it may result in erroneous predictions of risk for renal failure and response to therapy. 2 figures. 5 tables. 39 references. (AA-M).
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Systemic Lupus Erythematosus: Emerging Concepts. Part 1: Renal, Neuropsychiatric, Cardiovascular, Pulmonary, and Hematologic Disease Source: Annals of Internal Medicine. 122(12): 940-950. June 15, 1995. Summary: This article reports on a review of advances and controversies in the diagnosis and management of systemic lupus erythematosus with visceral involvement (renal, neuropsychiatric, cardiopulmonary, and hematologic disease). The authors reviewed more than 400 English language articles in the medical literature. They note that recent debates pertaining to lupus nephritis have focused on the value of kidney biopsy data and the role of cytotoxic drug therapies. Many studies have shown that estimates of prognosis are enhanced by consideration of clinical, demographic, and histologic features. For patients with severe lupus nephritis, an extended course of pulse cyclophosphamide therapy is more effective than a 6-month course of pulse methylprednisone therapy in preserving renal function. They conclude that the optimal duration and intensity of cytotoxic therapy remain undefined. 3 figures. 3 tables. 124 references.
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Renal Vascular Lesions in Lupus Nephritis Source: Medicine. 76(5): 355-368. September 1997. Contact: Available from Lippincott Williams and Wilkins. 227 East Washington Square, Philadelphia, PA 19106. (800) 638-6423.
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Summary: This article reports on a study of a series of 169 kidney biopsies performed between 1980 and 1994 in 132 patients with lupus nephritis (LN). The biopsies were performed to obtain a comprehensive clinical and histologic description of the intrarenal vascular lesions in LN and, more specifically, to clarify two incompletely resolved issues: first, to outline the clinical manifestations associated with the different types of renal vascular lesions and the prognostic significance of each; second, to better understand the so-called lupus vasculopathy (also called noninflammatory renal microangiopathy, renal angiitis, and other names). The terms used suggest that blood clotting and endothelial lesions are involved; however, the research reported in this article does not support these mechanisms. The authors favor the hypothesis that lupus vasculopathy could in fact be due to formation of immunoglobulin microvascular casts. The authors call for a better description of the clinical significance of these renal vascular lesions in LN, with particular attention to lupus vasculopathy. The most common vascular lesions were nonspecific sclerotic changes, found in 37 percent of the biopsies; the other common vascular lesions were immunoglobulin microvascular casts (24 percent of biopsies). Vasculitis and thrombotic microangiopathy were rare lesions (2.4 percent and 0.6 percent of cases, respectively). The authors conclude that, taken as a whole, their data confirm that the presence of active and severe forms of diffuse proliferative LN (WHO class IV) carries a worse prognosis compared with the other forms of LN. The long term renal survival of patients with class IV LN was significantly worse than that of patients with other forms of LN, with a 10 year renal survival of 70 percent compared with 85 percent, respectively. However, the data do not support the conclusions of some previous studies that the presence of intrarenal vascular lesions is a marker of poor renal prognosis in LN. 4 figures. 8 tables. 43 references. (AA-M). •
Maternal and Fetal Complications in Pregnant Women with Systemic Lupus Erythematosus Source: American Journal of Kidney Diseases. 17(2): 123-126. February 1991. Summary: This article reviews recent studies that provide important insights into maternal complications in patients with systemic lupus erythematosus (SLE) established before onset of pregnancy. Exacerbations or relapse occur during the course of pregnancy and immediately postpartum in 25 to 60 percent of pregnancies. However, the likelihood of increased clinical activity of SLE during pregnancy is influenced by signs of activity present at onset of pregnancy. The introduction of an assay for anticardiolipids has led to a new concept for the pathogenesis of autoimmune disease, namely immune-related thrombosis. Recent studies suggest that this mechanism may play an important role in clinical episodes in SLE, involving late fetal death and maternal arterial and venous thrombosis. 2 tables. 21 references. (AA-M).
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Systemic Lupus Erythematosus: A Review for Dental Professionals Source: Journal of Dental Hygiene. 72(2): 35-40. Spring 1998. Summary: This article reviews, for dental professionals, systemic lupus erythematosis (SLE), a chronic, autoimmune disorder of unknown etiology with an annual incidence of 2 to 8 cases per 100,000 adults. Symptoms include fevers, arthralgias, and a characteristic rash over the cheeks and nose. More serious manifestations involve the cardiac, renal, and central nervous systems. Due to the valvular damage associated with SLE, prophylactic antibiotic premedication is recommended prior to invasive dental procedures. Drug therapy consists of nonsteroidal anti-inflammatory agents, antimalarials, and corticosteroids. The appropriate dental management of these patients requires an understanding of the etiology, clinical manifestations, current treatment
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recommendations, and psychological aspects of the disease. The authors note that the clinical course of systemic lupus erythematosus is unpredictable, marked by exacerbation and remission. During periods of disease flare-up, patients with SLE may find dental treatment taxing. Adjusting the dosage of corticosteroid medications may be necessary to prevent adrenal crisis. The pain and fatigue associated with the disease may require temporary postponement of elective procedures. The psychological condition of the SLE patient must also be considered when planning treatment. 3 figures. 1 table. 28 references. (AA-M). •
Lupus: High-Stakes Dx, Broad Treatment Options Source: Patient Care. 32(4): 105-106, 109-110, 112, 115-116, 118, 123. February 28, 1998. Summary: This journal article explains for health professionals the diagnosis and management of systemic lupus erythematosus (SLE). This chronic autoimmune disease is more common in women than in men, and its severity can vary markedly among patients. Disease flares can be followed by periods of remission. Diagnosis is based on the medical history, a physical examination, and selected laboratory tests. Symptoms may include a malar rash, arthritis, mouth sores or nasal ulcers, swollen hands or ankles, weight loss, fever, hair loss, and chest pain. Laboratory studies are important to the diagnosis, and the fluorescent antinuclear antibody test and the rheumatoid factor test are commonly performed. The anti-DNA and the anti-Sm antibody tests are considered diagnostic markers, and a classification system developed by the American College of Rheumatology can be used as a guide. Treatment should begin as early in the disease course as possible. Nonsteroidal anti-inflammatory drugs and antimalarials are the most commonly prescribed agents for milder manifestations, while more severe ones require corticosteroids and cytotoxic drugs. Also, patients should be counseled on lifestyle changes that may help counter some of their nonspecific symptoms. Once the treatment plan has been established, patients with active disease should visit their primary care physician every 3 to 6 weeks and their rheumatologist once or twice a year. Although the prognosis has improved, physicians need to be aware of the various complications of SLE and how to prevent them. 1 figure, 1 table, and 6 references.
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Revisiting Autoantibody Profiles in Systemic Lupus Erythematosus Source: Journal of Rheumatology. 24(2):297-302; 1997. Summary: This journal article for health professionals describes a study that reexamined the use of autoantibody profiles to gain information about the pathogenesis of systemic lupus erythematosus (SLE). Sera of 68 patients with SLE were assayed for autoantibodies by ELISA or immunoprecipitation. Specificities were grouped into sets, including double stranded (ds) deoxyribonucleic acid (DNA) or histone, U1 RNP or Sm, Ro or La, ribosomes, Ku, Ki, and others. An analysis was also performed of reported SLE autoantibody profiles. Results indicate that the prevalences of autoantibody sets included the following: dsDNA or histone, 59 percent; U1 RNP or Sm, 40 percent; Ro or La, 41 percent; ribosomes, 4.4 percent, Ku, 4.4 percent; and Ki, 2.9 percent. On average, autoantibody positive patients had two to three autoantibodies and about two to three autoantibody sets. This finding is consistent with a retrospective analysis of past studies. Data further support a model in which global immune dysregulation in SLE leads to organ-specific autoimmunity against particular ubiquitous autoantigens. 35 references, 2 figures, and 3 tables. (AA-M).
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Predicting Complications From Lupus Source: Arthritis Today. 22-23; March-April 1998. Summary: This journal article for individuals with arthritis, doctors may soon have a test to predict which individual with lupus is at risk for lupus nephritis. The test helps determine which type of Fc gene individual with lupus has. One variant of this gene produces receptors that bind well to antibodies, and the other leads to receptors that leave unacceptable numbers of antibodies in circulation. Research has shown that most of the individuals with lupus have two copies of the poorly binding variant. Other studies have shown that many lupus patients with kidney disease also have two copies of the inefficiently binding gene.
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Cutaneous Manifestations of Rheumatic Diseases: Lupus Erythematosus, Dermatomyositis, Scleroderma Source: Dermatology Nursing. 10(2): 81-95. April 1998. Summary: This journal article presents nurses and other health professionals with information, which is part of a continuing education series, on recognizing and managing the cutaneous manifestations of rheumatic diseases. It discusses the classification, diagnosis, clinical features, and management of skin disease seen in patients with lupus erythematosus (LE), dermatomyositis (DM), and scleroderma/systemic sclerosis. The cutaneous manifestations of LE can be divided into those that are histologically specific and those that are not. Each LE-specific skin disease produces a particular type of skin lesion. Patients with LE are photosensitive, so they should protect their skin from sun exposure. In addition, patients with LE may be treated with topical and intralesional corticosteroids, antimalarials, nonimmunosuppressive anti-inflammatory drugs, and immunosuppressives. A cautious approach should be used with regard to surgery. DM is characterized by skin lesions and a histopathologically specific pattern of skeletal muscle inflammation. Patients should use sunscreens, and they may be treated with topical antipruritics, antihistamines, antimalarials, prednisone, and other drugs. Scleroderma, which has two forms, is characterized by thickened, hardened, leather-like skin. The initial manifestation of localized scleroderma is asymmetrical circumscribed indurated plaques on the truck or proximal extremities that are often surrounded by a halo of violaceous skin. Systemic sclerosis, the second form, usually begins with Raynaud's phenomenon. The same moisturization and antipruritic measures described for DM should be used for scleroderma: that is systemic antibiotics, vasodilators, anticoagulants, immunosuppressive drugs, and various investigational approaches. 8 figures, 7 tables, and 21 references.
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Lupus: Mysterious Disease Holds Its Secrets Tight Source: Science. 296: 689-691. April 26, 2002. Summary: This journal article provides health professionals and people who have lupus with information on lupus research. In people who have this disease, the immune system goes awry and turns its cell killing forces against the host. Symptoms can range from mild to severe, and they flare and recede over time. Damage can affect almost any organ in the body. The majority of patients are women, and African American women are three times as likely to get lupus as white women. The peak incidence is between the ages of 15 and 40, so estrogen has long been considered a key risk factor. Although scientists have proposed numerous causes, they agree that, while environmental factors are important, just as critical are inherited genetic traits that make a person's immune
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system susceptible to dysregulation. Animal studies suggest several ways this interaction between environment and genetics might lead to chronic disease. One pathway is a hyperactive immune system that responds too aggressively to foreign stimuli and fails to turn off when it should. A second pathway involves a deficient rather than a hyperactive immune system. Some researchers argue that people develop lupus because they have flaws in complement, a multistage immune response that helps clear dead material from the body. Researchers have found several environmental agents that seem to trigger lupus, including exposure to sunlight, certain prescription drugs, viruses, and bacteria. Immunologic research is focusing on the role of anti-DNA antibodies in lupus, while molecular biological research is seeking genes that may be involved in its etiology. Several biotechnology companies have launched clinical trials testing novel proteins for lupus therapy. The article also includes information on a new source of funding for lupus research. 3 figures. •
Neonatal Lupus Erythematosus Source: Dermatology Nursing. 14(3): 157-160. June 2002. Summary: This journal article provides nurses with information on the pathogenesis, clinical manifestations, diagnosis, and treatment of neonatal lupus erythematosus (NLE). Although the exact incidence of NLE is unknown, it appears to occur in about 1 in 20,000 live births and can affect all ethnic groups. The pathogenesis of NLE involves the anti-Ro and anti-La antibodies, but their presence does not necessitate clinical disease. The most common manifestations of NLE are distinctive, nonscarring skin lesions and congenital heart block (CHB). Most NLE infants will have lesions on the face and scalp. Extremity lesions are also common. Half of NLE neonates will have CHB, and the heart block is often complete. The mycocardium can also be affected in NLE. Other extracutaneous findings include hepatic disease, thrombocytopenia, and neutropenia. The diagnosis of NLE should be suspected based on the maternal history of anti-Ro/La antibodies, a previous child with NLE, or autoimmune disease. A neonate who has cutaneous lesions, but with a questionable diagnosis, should have a skin biopsy taken. The treatment for the cutaneous lesions involves strict sun avoidance and use of mid to low potency topical steroids. There is no firm consensus regarding the management of CHB. Infants with NLE are at risk of developing other autoimmune diseases during childhood or adolescence. 3 figures and 18 references.
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Systemic Lupus Erythematosus: When Your Immune System Attacks You Source: Healthline. p. 16-20. November-December 2000. Summary: This journal article provides people who have systemic lupus erythematosus (SLE) with up to date information on the causes, manifestations, diagnosis, and treatment of this autoimmune disease. The article begins with a brief historical review of lupus and an explanation of the physiology of the immune system. SLE is caused by an combination of hereditary susceptibility, immune system deficiencies, and environmental triggers. It occurs mainly among young women in their childbearing years. The difference in the manifestation of lupus in men and women can be explained by the hormonal influences of estrogen. Lupus manifestations vary from one patient to another. Diagnosis is based on the presence of 4 or more of 11 criteria that the American Rheumatic Diseases Association published in 1982. Drugs used to treat lupus include nonsteroidal antiinflammatory drugs, steroids, immunosuppressive drugs, and antimalarial drugs. The article explains how these drugs work and presents their side effects. In addition, the article offers suggestions on living with lupus.
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Antiphospholipid (Hughes) Syndrome in Systemic Lupus Erythematosus Source: Rheumatic Disease Clinics of North America. 26(2): 331-348. May 2000. Summary: This journal article uses a question and answer format to provide health professionals with information on the clinical features, diagnosis, and management of antiphospholipid syndrome (APS) in systemic lupus erythematosus (SLE). APS occurs in approximately 30 percent of patients who have SLE. Clinical features and antiphospholipid antibody (aPL) specificities are similar between the primary and secondary forms of APS. Major features of APS include thrombosis, cytopenias, recurrent pregnancy loss, and cardiac valve lesions. The clinical course of the secondary syndrome is independent of the activity and severity of lupus, but the presence of APS worsens the prognosis. Lupus anticoagulant and anticardiolipin antibody tests confirm APS. Preliminary classification criteria consider that APS is present when one or more clinical and one or more laboratory criteria occur in the same patient. The differential diagnosis of APS includes autoimmune diseases, malignancies, drug induced disease, infectious diseases, and vasculitis. Treatment for APS remains empirical and directed at coagulation and immune mechanisms because of the limited amount of controlled prospective data. There is strong evidence that patients with aPL associated thrombosis are subject to recurrences and require prophylactic therapy. The treatment of choice for recurrent fetal loss is anticoagulation with heparin. 85 references. (AA-M).
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Lupus Erythematosus: 'Reading' the Skin for Diagnostic Clues Source: Consultant. 39(4): 1173-1176,1179-1180,1183-1184,1189-1190. April 1999. Summary: This journal article, the first in a three-part series on connective tissue diseases, provides health professionals with information on the classification, pathogenesis, diagnosis, treatment, and prognosis of the various types of cutaneous lupus erythematosus. The fundamental defect in lupus erythematosus occurs in the immune system. Cutaneous manifestations of lupus erythematosus offer clues to its diagnosis. The classic form of chronic cutaneous lupus erythematosus (CCLE) is characterized by discoid lesions with well-demarcated, erythematous, slightly infiltrated plaques and associated thick adherent scale with follicular plugging. Lesions can be localized or generalized, with involvement of the skin both above and below the neck. The classic subtypes of CCLE include hypertrophic lupus and lupus panniculitis. Both the papulosquamous and annular forms of subacute cutaneous lupus erythematosus (SCLE) may be distinguished from CCLE by the absence of thick adherent scale, follicular plugging, and atrophy. The lesions of acute cutaneous lupus erythematosus appear as either malar erythema or a generalized vesiculobullous or morbilliform eruption. Infants who have neonatal lupus erythematosus generally exhibit lesions similar to the papulosquamous and annular ones seen in SCLE; however, adherent scale, atrophy, and follicular plugging are occasionally observed. Useful diagnostic tests include hematologic profiles and immunofluorescent studies. Physicians should keep in mind that various drugs, such as procainamide, hydralazine, isoniazid, and methyldopa, can cause a lupus-like reaction. The management of cutaneous lupus erythematosus involves both topical and systemic therapy. The course of lupus erythematosus is highly variable. 10 figures, 5 tables, and 30 references. (AA-M).
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Treatment of Lupus Nephritis: A Work in Progress (editorial) Source: New England Journal of Medicine. 343(16): 1182-1183. October 19, 2000. Summary: Until the pathogenesis (development of disease state) of nephritis (kidney infection) due to systemic lupus erythematosus (SLE) is unraveled, optimal treatment
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for patients with this disease remains an elusive goal. This article outlines one option for treatment of lupus nephritis, serving as an introduction to a separate article in this issue of the Journal. The author first reviews the differing presentations of SLE, noting that in some patients the kidneys are not involved but in others, there is rapidly progressive destructive kidney disease. This difference may be due in part to genetic risk factors, to environmental factors (such as exposure to ultraviolet light, infectious pathogens, and silica dust), race, or socioeconomic factors. In general, the treatment of lupus glomerulonephritis depends on the severity of the disease. Intravenous cyclophosphamide is given, in addition to oral glucocorticoids, for the aggressive forms of the disorder. However, the adverse effects of these therapies have prompted the search for alternative treatments. The author then comments on the accompanying article which presents the results of a study in which patients with diffuse proliferative lupus nephritis were successfully treated with prednisolone and mycophenolate mofetil. The editorial author notes that there are several reasons for caution before generalizing these findings to other patients with proliferative lupus glomerulonephritis, notably underrepresentation of patients with poor prognosis and certain demographic characteristics. 10 references.
Federally Funded Research on Lupus The U.S. Government supports a variety of research studies relating to lupus. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to lupus. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore lupus. The following is typical of the type of information found when searching the CRISP database for lupus: •
Project Title: A TRANSGENIC MODEL FOR B CELL TOLERANCE AND AUTOIMMUNITY Principal Investigator & Institution: Erikson, Jan S. Associate Professor; Wistar Institute Philadelphia, PA 191044268 Timing: Fiscal Year 2001; Project Start 01-DEC-1991; Project End 30-NOV-2004 Summary: A hallmark of systemic lupus erythematosus (SLE), and murine models of lupus, is the presence of anti-double-stranded (ds) DNA Abs. Our goals are to understand how SLE-associated autoantibodies are regulated in healthy individuals and to identify the mechanisms underlying their expression in autoimmunity. The approach we have taken is to develop a transgenic (Tg) model using a heavy chain-only Tg
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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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(VH3H9) which can pair with endogenous light chains to generate a spectrum of antiDNA and non-DNA antibodies (Abs). The advantage of this model is that the development of anti-dsDNA B cells can be tracked in the context of a diverse B cell repertoire in non- autoimmune and autoimmune-prone backgrounds. Aim 1 of this competitive renewal is to compare the effects of distinct genetic mutations that are known to result in the production of SLE-associated autoantibodies on the phenotype and functional capacity of anti-dsDNA B cells. Specifically, lpr/lpr, gld/gld, and lyn-/mice will be studied. Furthermore, the regulation of dsDNA B cells will also be investigated in induced models of SLE. Using the VH3H9 Tg in MRL-lpr/lpr mice, we have identified changes in the developmental status and tissue localization of antidsDNA B cells that precede autoantibody production. Aim II is to understand the mechanisms behind these phenomena, with particular emphasis on identifying the role that defective Fas (lpr/lpr) plays in autoantibody expression. Aim III is to characterize the nature and significance of the CD4 T cells that co-localize with anti-dsDNA B cells in MRL-lpr/lpr mice. The novel aspect of the proposed studies is that, in the context of the VH3H9 Tg, we can follow the fate of anti-dsDNA B cells under diverse circumstances to begin to identify steps that lead to autoantibody production. Knowledge of the parameters that influence the production of autoantibodies may inspire more targeted therapy for SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACE INHIBITORS AUTOANTIBODY PRODUCTION
IN
LUPUS
NEPHRITIS--TGFB
AND
Principal Investigator & Institution: Singh, Ram R. Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, OH 45229 Timing: Fiscal Year 2001; Project Start 15-MAR-2001; Project End 28-FEB-2006 Summary: Angiotensin-converting enzyme inhibitors (ACEIs), such as captopril, are widely used to control hypertension in patients who have chronic renal disease. ACEIs improve renal function in patients with chronic renal disease, however, than would be expected from their suppression of hypertension. ACEI-induced improvement in renal function is associated with decreased renal TGF-beta expression and matrix deposition. We anticipate that ACEIs may have a similar effect on TGF-beta production, renal fibrosis and end stage renal disease in patients with lupus. However, because TGF-beta can inhibit T and B cell activation and auto-antibody productions, an ACEI-induced decrease in TGF-beta may exacerbate auto-antibody-mediated disease in lupus by enhancing auto-antibody production. Consequently, this proposal will explore potential therapeutic and damaging effects of ACEIs in SLE, inflammatory component of lupus nephritis, its continued presence enhances renal matrix deposition and fibrosis. To test this hypothesis we will: 1) evaluate autoantibody responses and renal disease in lupusprone mice treated with ACEIs; and 2) generate and characterize mice that have kidneyspecific deletion of the Tgfb1 gene. These mice will be used in future to determine the effect of TGF-beta deletion on lupus nephritis. Lupus-prone and control mice will be treated with captopril or a control anti-hypertensive agent; the effect on blood pressure, renal functions, renal histology, renal immune and collagen deposition will be determined. These changes will be correlated with TGF-beta expression in kidneys and spleens, and serum auto-antibodies. We will then generate mice that have renal-specific Tgfb1 gene deletion, and characterize their phenotype, specifically for any inflammatory changes in kidneys and other organs. The broad objectives of this proposal are to understand the role of TGF- beta in the pathogenesis of lupus nephritis, to explore how manipulation of in vivo TGF-beta can influence lupus, and to elucidate the mechanism
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and clinical utility of ACEIs in lupus. Delineation of pathways that cause matrix deposition in kidneys, but do not affect T and B cell activation, may lead to treatment strategies that improve end stage renal disease in SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADAPTATION /COGNITIVE BEHAVIOR THERAPY FOR SLE Principal Investigator & Institution: Brown, Ronald T.; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: The purpose of this program is to enhance the adjustment and quality of life in adolescents with systemic lupus erythematosus (SLE). The theoretical rationale is based on the Investigators' program of research in the validation of models in pediatric psychology designed to predict adjustment and adaptation in children and adolescents with chronic illness. To accomplish this purpose, the first aim of the investigation is to assess the associations between adaptational processes and adjustment and healthrelated quality of life in female adolescents with SLE. A major hypothesis of the study aim is that adaptational processes including methods of coping, expectations of selfefficacy, and social support will account for a significant proportion of the variance in adjustment and health-related quality of life after controlling for demographic characteristics and disease parameters. It also is hypothesized that methods of coping, expectations of self-efficacy, and social support will independently mediate the association between severity of disease and adjustment and health-related quality of life. The second aim of the investigation is to conduct a controlled randomized manualizedbased trial designed to enhance adjustment and quality of life in female adolescents with SLE. The hypothesis of the study aim is that the manualized-based cognitivebehavioral intervention will lead to improvements on measures of adjustment and quality of life in comparison to an education-only control group and a no-contact control group. Finally, it is hypothesized that the benefits of the manualized intervention will persist over a six-month follow-up period. To accomplish the objectives of this program of research, female adolescents diagnosed with SLE ranging in age from 12 to 18 years, the majority of whom are African-American, will serve as participants. Data to bc obtained from the participants will include periodic assessments of pain, methods of coping, expectations of efficacy, social support, negative affecxtivity, perceptions of physical appearance, social competence, and health-related quality of life. In addition, caregivers and teachers also will report on the adolescents' general adjustment, while physicians will complete measures of disease severity. It is anticipated that the 147 patients will be randomized to the three arms of the intervention trial. The research study proposed here will add to the extant literature by validating mediational processes of adjustment and quality of life in adolescents with SLE and will also validate empirically a cognitive behavioral therapy intervention program that has been demonstrated in other research to alter maladaptive cognitions and increase the use of selective coping skills, thereby enhancing adjustment and quality of life for individuals with a chronic disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ALPHA-ACTININ /RENAL PATHOGENICITY OF ANTI-DNA ANIBODIES Principal Investigator & Institution: Putterman, Chaim; Assistant Professor; Yeshiva University 500 W 185Th St New York, NY 10033
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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Antibodies against double stranded (ds) DNA are a characteristic serologic hallmark of SLE. While it has been demonstrated that anti-dsDNA antibodies play a critical role in the pathogenesis of lupus nephritis, the mechanisms of injury are incompletely understood. Experimental evidence strongly suggests that a least some anti-dsDNA antibodies are pathogenic by virtue of their direct cross reactivity with renal antigen. We recently demonstrated that a pathogenic anti-dsDNA antibody (R4A) binds to a 100 kD protein expressed on the cell surface of a mesangial cell line derived from a lupus-prone MRL-lpr/lpr mouse, and that DNAse treatment of the lysate does not affect binding. Binding was greatly diminished in lysates of mesangial cell line derived from a non-autoimmune mouse, suggesting that antigen expression and/or availability at the level of the target orphan may be a factor in determining susceptibility to lupus nephritis. Following identification of the 100 kD protein bound by R4a as alpha-actinin, the binding of R4A to alpha-actinin was confirmed by Western blot, ELISA, immunofluorescence, and inhibition studies. High titers of anti-alpha-actinin antibodies were found in sera and kidney eluates of lupus mice with nephritis, and in sera of lupus patients. The goals of this proposal are to study if cross-reactivity with alpha-actinin may be an important determinant of the renal pathogenicity of some antiDNA antibodies, and if the expression of alpha-actinin is genetically regulated and modulated by gender and exposure to cytokines. We will determine if anti-alpha actinin antibodies are pathogenic and if they cross-react with dSDNA, by immunization of mice with alpha actinin and studying the anti alpha-actinin antibody response in normal and autoimmune mice. The molecular basis for the differential levels of antigen display of alpha-actinin between autoimmune and non-autoimmune mouse strains will be studies, and the effects of age, gender, and cytokines known to be present in lupus kidneys on alpha-actinin expression and antibody binding will be determined. Finally, we will identify the epitopes of alpha-actinin that are recognized by pathogenic anti-dsDNA antibodies to understand the generation of anti-alpha actinin antibodies, and determine the potential of alpha-actinin peptides in the treatment of acute lupus nephritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS OF APOLIPOPROTEIN H IN LUPUS Principal Investigator & Institution: Kamboh, M Ilyas. Professor; Human Genetics; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 31-MAY-2007 Summary: (provided by applicant): The risk of coronary heart disease (CHD) in systemic lupus erythematosus (SLE) women is up to 50 times higher than in the general population. The conventional risk factors are insufficient to explain premature CHD in SLE patients. Compared to about 1-5 percent prevalence of antiphospholipid antibodies (APA) in the general U.S. white population, about 50 percent of the SLE patients are positive for APA. ApoH is a principal autoantigen for the production of APA in patients with autoimmune diseases. ApoH inhibits the in vitro uptake of oxidized low-density lipoprotein (oxLDL) by macrophages, but in the presence of APA it promotes the ihflux of oxLDL into macrophages. As the accumulation of oxLDL in macrophages is believed to initiate the atherosclerotic process, these findings suggest that apoH-mediated immune response in patients with autoimmune diseases, like SLE, may lead to atherosclerosis. In this renewal we propose to examine the joint roles of APA, antibodies to oxLDL (anti-oxLDL) and APOH genetic variation (known and discovered as part of this proposal) in relation to the occurrence of CHD in SUE and non-SLE patients. Our hypothesis is that individuals positive for APA and/or anti-oxLDL are prone to
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premature CHD and this susceptibility is modified by common genetic variation in the APOH gene. The objectives of the study will be achieved by fulfilling the five aims. Aim 1) identify and characterize naturally occurring common mutations in all exons, introns and the 3' region of the APOH gene by polymerase chain reaction (PCR), denaturing HPLC analysis and DNA sequencing in SLE and non-SLE CHD patients, and African blacks positive for APA. Aim 2) determine the prevalence and correlation between APA (anti-apoH, anticardiolipin, lupus anticoagulant) and anti-oxLDL in plasma samples from SLE patients and controls. Aim 3) determine the relationship between APOH genetic variation (data generated in Aim 1) and the occurrence of APA and anti-oxLDL (data generated in Aim 2). Aim 4) examine the relationship between APOH genetic variation (data generated in Aim 1) and the occurrence of subclinical cardiovascular events in SLE patients and with coronary atherosclerosis in non-SLE patients. Aim 5) perform in vitro mutagenesis and expression studies to express different apoH allelicisoforms to evaluate isoform-specific inhibition of LDL oxidation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIBODIES WITH PROTHROMBINASE ACTIVITY IN LUPUS Principal Investigator & Institution: Thiagarajan, Perumal; Professor of Pathology & Medicine; Internal Medicine; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-OCT-2001 Summary: Prothrombin is the precursor of thrombin, the central enzyme in blood coagulation. Prothrombin binding autoantibodies from lupus patients are clinically associated with thrombosis, but the association is paradoxical, because conventional mechanisms of antibody action predict decreased thrombus formation (e.g., antibody mediated inhibition of prothrombin activation by factor Xa; accelerated prothrombin clearance). In Preliminary Studies, we identified a new and potent mechanism by which these antibodies can induce thrombosis, i.e. the catalytic cleavage of prothrombin. This proposal is based on the hypothesis that prothrombinase autoantibodies promote thrombus formation by generating thrombin-like activities from prothrombin, like factor Xa, the physiological activator of prothrombin. The turnover capability of prothrombinase antibodies suggests that they can exert substantially more potent biological effects than reversibly binding stoichiometric antibodies. The products of prothrombin processing, i.e., thrombin (or thrombin-like fragments) are also catalysts, which will further amplify the procoagulant effect of the prothrombinases compared to reversibly binding antibodies. The specific aims are: to determine the statistical correlation of prothrombinase activity to thrombosis in lupus patients; define the biochemical characteristics of the prothrombinase autoantibodies relevant to their potential clinical effects; clone catalytically efficient prothrombinase Fv constructs from lupus patients for mechanistic studies; determine the procoagulant effects of the antibody-generated prothrombin fragments using in vitro model systems; and, determine whether the Fv constructs administered to mice induce thrombosis. To these ends, the prothrombin cleaving activity of polyclonal IgG from lupus and normal subjects will be compared by electrophoretic, fluorimetric and radiometric methods; affinity purified anti-prothrombin antibodies will be analyzed to determine kinetic parameters, specificity, cleavage sites, cofactor requirements, and enzymatic activity of prothrombin fragments; recombinant prothrombinase Fv constructs will be isolated from phage display libraries by selection using prothrombin and chemically reactive antigen analogs reactive with serine protease-like catalytic sites found in autoantibodies; the ability of antibody-generated prothrombin fragments to mimic the procoagulant
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effects of thrombin on fibrinogen, coagulation factors V, VIII and XI, and platelets will be determined in vitro by measuring fibrin formation, cleavage and activation of the various coagulation factors and protease activated receptor 1 on platelet. The prothrombotic effects of prothrombinase Fv administered to mice will be determined by measuring depletion of circulating prothrombin, consumption of coagulation factors and enhanced occlusion of the femoral vein. These studies will permit assessment of the extent to which the prothrombinase autoantibodies contribute toward the hypercoagulable state in lupus. If our hypotheses are valid, our studies can be extended to ameliorating the thrombotic events in lupus via inhibition of the prothrombinase activity of the autoantibodies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIC5 THERAPY OF LUPUS NEPHRITIS Principal Investigator & Institution: Holers, Michael; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001 Summary: This is an investigator-initiated collaborative Phase II treatment study in which we will examine the hypothesis that treatment of patients with systemic lupus erythematosus (SLE) and active lupus nephritis with a blocking anti-human complement C5 monoclonal antibody will lead to objective improvement in renal disease parameters. The anti-C5 monoclonal antibody will lead to objective improvement in renal disease parameters. The anti-G5 monoclonal antibody will be provided by Alexion Pharmaceuticals. Several lines of investigation have supported the concept that C5 plays a central role in renal injury in antibody- mediated diseases such as SLE. While short term studies using a similar inhibitor have shown efficacy in patients with inflammatory complications of coronary artery bypass surgery, the proposed study represents the first application of this therapeutic strategy, chronic inhibition of complement C5 activation, to patients with autoimmune diseases. Patients enrolled in this double blinded, placebo controlled Phase II study will be those who have active but clinically stable nephritis and, thus, do not require immediate introduction of high dose cyclophosphamide or other cytotoxic drug therapy. Two patient groups, treated and untreated (vehicle control only as a placebo), will be studied. The primary outcome variable will be proteinuria. Secondary outcomes will include other measures of renal disease activity, other measures of lupus activity and measure of complement activation. Three Specific Aims will be pursued. Specific Aim #1. Determine the changes in renal disease activity that accompany short term treatment with an anti-C5 monoclonal antibody in patients with active lupus nephritis. Specific Aim #2. Identify changes in levels of complement activation fragments that accompany treatment with anti-c5 monoclonal antibody in patients with active lupus nephritis. Specific Aim #3. Assess these patients treated with an inhibitory anti-C5 monoclonal antibody for evidence of toxicity. This study is integrated into other components and goals of the Denver Autoimmunity Center itself in several ways. First, it utilizes a population of patients drawn from several sources in the Denver Autoimmunity Center. Second, it meets the goal of extending the use of complement inhibitors from animal models, which are being extensively studied here in the laboratory of the P.I. and others, into clinical trials in patients. Third, the analysis of the role of complement inhibitors as compared to cytokine inhibitors is a major component of the Basic Science Project #2 headed by Dr. William P. Arend. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies 21
•
Project Title: ANTICARDIOLIPIN PHOSPHOLIPIDS
ANTIBODIES
AND
OXIDIZED
Principal Investigator & Institution: Witztum, Joseph L. Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 01-JAN-1997; Project End 31-JUL-2005 Summary: Patients with the antiphospholipid antibody syndrome (APS) have autoantibodies to certain phospholipids (aPL) such as cardiolipin and/or the lupus anticoagulant and clinically experience recurrent venous or arterial thrombosis, history of fetal death and autoimmune thrombocytopenia. Increased aPL also appear to predict increased risk of stroke and myocardial infarction in otherwise healthy men as well. However, controversy exists about the target antigens of aPL, and even university laboratories cannot agree who has elevated aPL titers. In turn, clinical management is hampered by lack of an underlying hypothesis to explain why antibodies should form to such ubiquitous compounds as PL. We have developed the novel hypothesis that many aPL are directed against epitopes of oxidized PL (OxPL) and/or against covalent adducts of OxPL and associated PL binding proteins, such as beta2GPI. Our hypothesis suggests that states of enhanced lipid peroxidation, as occurs in inflammation or atherosclerosis, leads to oxidation of PL (such as in LDL or in membranes of apoptotic or dying cells) which creates neo self-determinants and immunogenic epitopes. The resultant autoantibodies can then target such neoepitopes in many tissues, and may have a variety of biological consequences. Cardiolipin (CL) is the most common PL used to test for aPL. We have shown that APS plasma bind exclusively to OxCL, or to OxCL adducts with beta2GPI, and not to native CL. We propose to further test our hypothesis by determining if antibodies to other OxPL are also present in sera from patients and mice with lupus- like syndromes. We will generate a panel of such aOxPL murine monoclonals from (NZWxBXSB) F1 males. Similar Fab and scFv antibodies will be generated from a human phage-display library. We will determine the epitopes to which they bind and their impact on in vitro and in vivo coagulation, with an emphasis on the Protein C pathway. We will treat lupus-prone mice with potent antioxidants to see if changes in aPL titers and/or other clinical parameters occur. Understanding the etiology of even some of the aPL should lead not only to development of more standardized assays, which should improve our ability to detect high risk individuals, but also to consideration of new therapeutic modalities for patients with aPL and APS (e.g. aggressive anti-inflammatory and/or antioxidant interventions). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIGEN DRIVEN SELECTION/TOLERANCE: AUTOIMMUNITY TO DNA Principal Investigator & Institution: Marion, Tony N. Professor; Molecular Sciences; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163 Timing: Fiscal Year 2001; Project Start 01-JUL-1988; Project End 31-AUG-2005 Summary: (Adapted from the Investigator's abstract): Systemic lupus erythematosus is a systemic autoimmune disease in humans and genetically predisposed mice. Antibodies to a variety of cellular antigens, mostly nuclear in origin, have been detected in lupus sera from mice and humans; however, the autoantibody for which there is the most compelling evidence for pathological relevance is antibody to DNA. Anti-DNA antibodies deposit in kidneys either as immune complexes or by binding directly to glomerular structures and initiate glomerulonephritis. The immunological basis for the generation of anti-DNA autoantibody in mice and humans has been difficult to
22 Lupus
elucidate. The goal of the applicant's research on "Antigen Driven Selection and Tolerance in Autoimmunity to DNA" continues to be directed toward understanding how autoimmunity to DNA is initiated and sustained at the level of individual DNAspecific B cells in autoimmune (NZB x NZW) F1 mice. The applicant's research efforts since the last competitive review of this project have continued to support the hypothesis that autoimmunity to DNA is both initiated and sustained as a clonally selective, antigenic-specific immune response to DNA most likely in the form of DNAprotein complexes. The research has continued to focus on experiments to understand how the specificity and specificity maturation of the autoimmune anti-DNA antibody response within individual (NZB x NZW) F1 mice and the DNA-peptide induced immune anti-DNA antibody response in normal mice proceed. The results have provided new information about B cell selection in the autoimmune response to DNA and the V region structures necessary for that selection to occur. In the applicant's continuing research efforts to understand how autoimmunity to DNA is initiated, they will test the hypothesis that autoimmunity to DNA is initiated by antigen-specific B cell stimulation in the absence of peripheral B cell tolerance induced by extracellular DNA or nucleosomes. The specific experimental aims to be pursued in the research proposed will be to determine what role, if any, germinal centers play in the specificity maturation that generates high avidity autoantibodies to native DNA. Proposed experiments will also determine the role of soluble DNA or nucleosomes in maintaining immunological tolerance to DNA. The experimental systems designed to complete the proposed research will include the use of (NZB x NZW) F1 mice transgenic for expression of antiDNA antibodies. These mice have an interesting autoimmune phenotype that make them highly suited for experiments to test the hypothesis that autoimmunity to DNA in (NZB x NZW) F1 mice derives from antigen-selective B cell stimulation in the absence of effective peripheral tolerance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTI-SM B CELL REGULATION Principal Investigator & Institution: Clarke, Stephen H. Professor; Microbiology and Immunology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2003; Project Start 15-JUL-1998; Project End 31-DEC-2007 Summary: (provided by applicant): The long-range goal of this work is to determine how B cell tolerance to self-antigens in systemic lupus erythematosus (SLE) is lost. The focus will be the response to the nuclear antigen Smith (Sm), which is unique to human and mouse SLE. We have shown that in non-autoimmune mice some anti-Sm B cells are regulated by negative selection (anergy, developmental arrest, central deletion), while others are positively selected into the marginal zone and B-1 subsets and are functional. This coexistence of negatively and positively selected B cells is unusual and suggests a possible model for the anti-Sm response. The hypothesis to be tested is that one or few positively selected anti-Sm B cells are activated initially, and that the antibody they produce activates additional anti-Sm B cells, including those that are negatively selected. In Aim 1 we will determine which mechanism(s) of anti-Sm B cell regulation are defective in autoimmune MRL and lpr mice by generating a series Ig H and L chain transgenic mice regulated by different mechanisms. These mice will be followed for anti-Sm B cell activation to identify the mechanism(s) activated. In Aim 2 we will determine whether the repertoire of anti-Sm B cells involved in the response expands during its course to include a larger repertoire of B cell clones. Whether anti-Sm antibodies generated early in the response can activate other anti-Sm B cells will also be
Studies 23
determined. In Aim 3 we will examine the anti-Sm response in human SLE. We can detect anti-Sm B cells in the peripheral blood of SLE patients and find that they express unusually high CD19 levels, although non-Sm binding naIve cells have unusually low CD19 levels. We will test the hypothesis that the anti-Sm response in human SLE is antigen-driven and that intra-clonal diversity and affinity maturation are additive through successive periods of active disease. In addition, we will test the hypothesis that the unusual pattern of CD 19 expression affects tolerance and activation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: APOPTOTIC CELLS AS IMMUNOGENS IN SLE Principal Investigator & Institution: Elkon, Keith B. Professor of Medicine; Medicine; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies to nucleoprotein antigens. We have shown that complement and certain acute phase proteins are deposited on the surface of apoptotic cells and facilitate phagocytosis of the dying cell. Based on the clinical observations that patients with deficiencies of the early complement components develop SLE, that mice deficient in Clq or SAP develop lupuslike autoimmunity and that Clq deficient mice have increased numbers of apoptotic cells in their kidneys, we propose that autoantibodies in SLE arise through failure to process and clear dying cells, particularly at sites of inflammation. To test this idea, we will perform the following studies: In Aim 1, we will define how complement is activated on the surface of dying cells and how pentraxins modulate this process. In Aim 2, we will determine which receptors on macrophages are engaged by different opsonins on the dying cells and will determine the consequences of receptor engagement in terms of anti- or pro-inflammatory cytokine production. In Aim 3, uptake and processing of dying cells will be examined in vivo using two different experimental systems under baseline and inflammatory conditions. The responses will be compared between wild type and mice deficient in opsonins (Aim 1) or receptors (Aim 2) implicated in phagocytosis of dying cells. These studies should elucidate whether the hypothesis proposed is correct. If correct, it will provide the solid scientific background from which to define the molecular basis of human SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AUTOIMMUNE REGULATION AND TCR REPERTOIRE IN SLE ANTI CD40L Principal Investigator & Institution: Chess, Leonard; Professor; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001 Summary: We hypothesize that there are four principal events in the development of SLE: (1) genes predisposing to SLE establish a T-cell repertoire capable of recognizing self peptides intrinsic to the autoimmune process of SLE: (2) previously tolerant autoreactive CD4 T cells: (3) regulatory mechanisms including the activation of TH1 and TH2 CD4+ T cell subsets as well as those involving CD8 T-cells fail, through processes such as clonal deletion or changes in the cytokine milieu and (4) injurious IgG autoantibodies develop through cognitive T-cell B-cell interactions and in concern with potentially self reactive T-cells induce tissue damage and disease. The overall aim of this grant is to study patients at different stages of SLE activity and to use the opportunity
24 Lupus
presented by an ongoing clinical trial of a humanized monoclonal antibody (moAb) to CD40L in systemic lupus erythematosis (SLE) to study the immunopathogenesis of SLE and the basic mechanisms of the therapeutic intervention in this disorder. In principle, interruption of the CD40 ligand-dependent pathway could down-modulate SLE activity by acting at the distal level of the cognitive T-B interaction involved in IgG autoantibody production or at the induction and regulation of autoreactive T-cell clones. These more proximal mechanisms for anti-CD40L treatment would diminish the number of autoreactive cells in the T cell repertoire. We propose to test hypotheses relating to both the immunopathogenesis of SLE and the basic mechanism of the therapeutic intervention using anti-CD40L treatment. Specifically our aims are: (1) To identify by PCR based spectratyping techniques and T cell receptor (TCR) sequencing, oligoclonal and putatively autoantigen-driven expansions of the CD4 alphabeta TCR repertoire in SLE patients compared with those treated with moAb to CD40L: (2) Identify changes in the T cell functional response to autoantigens including Ro, La. These functional studies will include assay of T-B interactions in T cell activation, tolerance and help assays and (3) directly study the regulatory interactions of TH1, TH2 cells as well as CD8+T cells in controlling the TCR repertoire in SLE during anti-CD40L treatment. In select patients we will directly study the function and repertoire of T cells at the site of inflammation (kidney) using HVS immortalization techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AUTOIMMUNE TOXICITY OF CHLORINATED COMPOUNDS Principal Investigator & Institution: Schiffenbauer, Joel; Associate Professor; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2001 Summary: It is estimated that upwards of 10 million Americans have some form of autoimmune disorder. It is clear that for most of these disorders both genetic and environmental factors contribute to the development and progression of disease. In specific disorders such as systemic lupus erythematosis, women of childbearing age are affected at a rate 9-10 times that of men, and data both from human and animal studies suggest that estrogens can have an adverse impact on the course of the autoimmune process. Recently considerable interest has focused on possible environmental factors that may contribute to the development of autoimmune disorders in general, and lupus in particular. Several chemicals have been shown to have estrogen-like effects, and one mechanism by which environmental toxicants might influence the appearance of severity of autoimmune diseases is by mimicking the effects of estrogen. Preliminary studies in our laboratory have found that three chlorinated pesticides (o,p'-DDT, chlordecone, and methoxychlor) previously shown to have estrogenic effects in vivo significantly accelerate the development of autoimmune disease in a lupus model, (NZB x NZW)F1 (or BW1) mice. A proposed series of experiments 3will extend these observations by establishing dose-response relationships for this effect for each of the three toxicants and determining on-effect levels. To facilitate extrapolation to other species including humans, body burdens in key tissues corresponding to these dosages will be determined. A related objective will be to determine whether autoimmune effects can be elicited by these agents following fetal and neonatal exposure or in a mouse strain that does not normally develop spontaneous lupus. The hypothesis that effects are due to estrogenic activity will be tested in mice administered an estrogen antagonist, and a potential mechanism will be examined. Using o,p'-DDT, methoxychlor, and chlordecone as prototype environment estrogenic autoimmune
Studies 25
disease, as well as provide important information regarding mechanisms through which immune function is altered by these agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: B CELL AUTOREACTIVITY IN ESTROGEN-INDUCED LUPUS Principal Investigator & Institution: Grimaldi, Christine M. Microbiology and Immunology; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The research plan outlined in this proposal will provide the opportunity to incorporate years of postdoctoral training in B cell immunology and predoctoral training in cellular, molecular and biological chemistry and to explore challenging new areas of B cell biology and autoinimunity. Interactions with the many, accomplished scientists at the Albert Einstein College of Medicine have provided a foundation to investigate cellular and molecular aspects of B cell regulation and tolerance induction. In conjunction with the dynamic research environment at AECOM, training will be enhanced by departmental and institutional seminars and courses. The long-term goal is to continue a research career as an immunologist and as an independent investigator in a medical research institution. Plans are described to perform research related to the understanding of the regulator, mechanisms associated with B cell development, B cell activation and autommunity using model systems of systemic lupus erythematosus (SLE). The effects of estrogen (E2) in the immune system and its role in SLE are poorly understood. Since there has long been suggestive evidence for a role of E2 in SLE, they have been studying the impact of E2 treatment on B cell tolerance. Examination of non autoimmunity mice that are transgenic for the heavy chain of a pathogenic anti DNA antibody revealed that a sustained increase in E2 disrupts normal B cell tolerance of anti DNA B cells and leads to an increase in anti DNA antibody titers, an expansion of anti DNA B cells and glomerular immunoglobulin deposition. The autoimmune phenotype observed in E2 treated mice is characterized by the altered distribution of splenic B cell subsets, with a diminished immature transitional population and an increase in marginal zone B cells. This shift in B cell development correlates with the increased number of in vivo activated marginal zone B cells that secrete anti DNA antibody. Since little is known about the role of the T cell independent marginal zone B cell immune response in autoimmunity, the E2 induced mouse model of lupus provides a system to explore the contributions of this B cell subset in B cell mediated autoimmune disorders. In an effort to delineate pathways that regulate the threshold for tolerization and activation, they will explore the hypothesis that E2 induced expression of CD22 and SHP 1 contributes to the escape of autoreactive B cells in this model of lupus. Results from these studies are intended to provide insight into the mechanisms of B cell tolerance, and, importantly, may help identify key regulatory pathways in patients in which disease is hormonally regulated, as well as in patients in which disease is not hormonally regulated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: B CELL FUNCTIONAL AND SIGNALING ABNORMALITIES IN SLE Principal Investigator & Institution: Anolik, Jennifer H. Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, NY 14627 Timing: Fiscal Year 2002; Project Start 26-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): It is thought that defects in the process of B lymphocyte tolerance are central to the pathogenesis of systemic lupus erythernatosus
26 Lupus
(SLE). Moreover, the importance of B cell receptor (BCR) signal strength for the regulation of tolerance is evident from murine models of autoimmunity which suggest that specific defects in lymphocyte signaling can lead to SLE-like phenotypes. In order to define tolerance mechanisms and test the above hypotheses in humans, they have developed a novel system to track self-reactive B cells. This system utilizes a specific antibody variable region gene segment, VH4.34, as a surrogate marker of autoreactivity. Preliminary results support the hypothesis that B lymphocyte tolerance is defective in SLE and is in particular perturbed during the naive to memory B cell transition. Exactly where and how tolerance is abrogated during this transition remains to be defined. The present proposal will focus on further refining the distribution of autoreactive B cells into distinct subsets by flow cytometry and immunohistochemistry along the naive to memory transition in peripheral blood and lymphoid tissue from lupus patients in order to determine specifically where tolerance is abrogated. Aim 2 will ask what the mechanism of tolerance escape is by characterizing defects in signaling and function in lupus naive B cells compared to normal controls and correlating this with loss of tolerance. Signal transduction will be measured by calcium fluxes, tyrosine phosphorylation, and recruitment of downstream signaling pathways. Functional analysis will include determination of proliferative responses and expression of activation markers. Aim 3 will define what happens to the above abnormalities after treatment with a specific immunotherapy that targets B cells in a systematic fashion. By enumerating B cell subsets and characterizing defects in signal transduction and function in lupus B cells before and after B cell depletion, they will further elucidate the critical role of B cells in the immunopathogenesis of SLE. Given the long-term goal of understanding the basic mechanisms underlying the loss of immune tolerance, as an academic rheumatologist, this project and career award combined with the interactive research environment and the mentoring available at the University of Rochester is intended to foster the candidate's development as a basic science immunologist and independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: B CELL TOLERANCE TO NUCLEAR ANTIGEN LA Principal Investigator & Institution: Farris, a Darise. Assistant Member; Oklahoma Medical Research Foundation Oklahoma City, OK 73104 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): A primary knowledge of normal mechanisms of immune tolerance to self constituents is required before the immunological events leading to autoimmunity can be understood. Much has been learned about T and B cell tolerance to membrane and secreted proteins in recent years, largely through the use of transgenic technology, but there is a gap in knowledge regarding normal mechanisms of immune tolerance to protein antigens of the nucleus. Yet the majority of autoantigens, like La/SS-B, targeted in a number of systemic autoimmune diseases including Sjogren's syndrome and systemic lupus erythematosus are composed of protein and localize to the nucleus. The highly conserved nature of these house-keeping proteins (and DNA) has hampered their study in relation to immune tolerance. Moreover, the pathways through which nuclear proteins become visible to the immune system may be fundamentally different from those of previously studied membrane and secreted self antigens. In order for tolerance and autoimmunity to nuclear antigens to be comprehended, a requirement for unraveling the etiology(ies) of systemic autoimmune disease(s), it is therefore imperative that nuclear proteins be studied as a special class of self antigen. To address these issues, B cell tolerance to the La nuclear antigen will be
Studies 27
investigated as a paradigm for protein antigens of the nucleus. These studies will utilize mice transgenic for the human La (hLa) gene in its natural form to allow the study of Laspecific B cells in environments where self antigen is either present or absent. By focusing on B cells that recognize human specific epitopes of the hLa neoself antigen, the existence and extent of tolerance to the hLa antigen in the B cell compartment will be determined. Both transgenic and homologous recombination technology will be used to clarify the nature of B cell tolerance to La and determine the mechanisms of its occurrence. These studies will advance our collective understanding of anti-nuclear autoimmunity underlying a constellation of rheumatic disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BONE MINERAL DENSITY IN SYSTEMIC LUPUS ERTHEMATOSUS IN CHILDREN Principal Investigator & Institution: Von Scheven, Emily; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001 Summary: The increased survival of children with Systemic Lupus Erythematosus (SLE) into adulthood has resulted in novel morbidities such as osteopenia and the associated increased risk of spontaneous vertebral compression fractures and fractures secondary to trauma related to sports and other normal childhood activities. Like other children with severe illness, these children are particularly susceptible to the development of osteopenia due to the limited window of time during childhood dedicated to achieving peak bone mass, and the critical role of peak bone mass in the future development of osteopenia. Additionally, individuals with SLE may be at particularly high risk for the development of osteoporosis due to their use of glucocorticoids, sunshine avoidance with possible vitamin D deficiency, renal disease with potential effect on vitamin D hydroxylation, and decreased activity due to severe illness and arthritis. Very few studies have been performed to evaluate bone mineral density (BMD) in children with SLE and thus neither the incidence nor the appropriate treatment is known. The proposed study will characterize the incidence and severity of osteopenia in pediatric SLE with particular attention to the bone age and sexual development of the child. Additionally, the study will begin the evaluate the clinical risk factors associated with osteopenia in this population. Identification of risk factors will ultimately contribute to the development of preventive and therapeutic interventions. The evaluation of BMD in the context of Tanner stage and bone age in this project may result in the development of bone age-specific treatment protocols for pediatric SLE. Furthermore, information gained from this research may have application to the study of osteopenia in other autoimmune disorders, such as rheumatoid arthritis; and to other patients receiving corticosteroids such as those with nephrotic syndrome and inflammatory bowel disease. The utilization of two densitometric techniques, Dual photon x-ray absorptiometry (DXA) and Single-energy quantitative computerized tomography (SEQCT) will permit us to address the current question of the most appropriate methodology for measuring bone mineral density in children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CD1 ERYTHEMATOSUS
RESTRICTED
T
CELLS
IN
SYSTEMIC
LUPUS
Principal Investigator & Institution: Sieling, Peter A. Associate Professor; Microbiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024
28 Lupus
Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 30-NOV-2003 Summary: The goal of this proposal is to investigate the role of CD1-restricted T cells in autoimmune disease using systemic lupus erythematosus (SLE) is a model. Pathogenic autoantibody production against non peptides in SLE is dependent upon T cell help, thus SLE represents an immunological enigma according to the existing paradigm of T cell recognition of peptide-only antigens. CD1 antigen presentation of non-peptide molecules in SLE produce IL-4 and recognize autoantigen presented by B cells in the context of CD1. We hypothesize that CD1-restricted T cells in SLE recognize non peptide antigens and provide help for B cells to produce autoantibodies against the same antigen, thereby contributing to the pathogenesis of autoimmune disease. To test this hypothesis we first propose to ascertain the restricting element and cytokine patter of CD1- restricted autoreactive T cells in SLE by deriving T cell lines and clones from the cutaneous lesions and blood of patients and compare them to T cell lines derived from healthy donors. Second we will investigate whether the cognate interaction of CD1crestricted autoreactive T cells and CD1c+ B cell deletion or activation. We will also investigate the role of CD1+ antigen presenting cells (APCs) in directing CD1 peptide antigens which stimulate CD1-restricted autoreactive T-cell responses. This final goal will be achieved by purifying the CD1c ligand from a soluble endogenously loaded CD1c and use the ligand to stimulate CD1-restricted autoreactive T-cells. The studies within this proposal should provide a comprehensive understanding of the interaction between T-B cells in the generation of immunoglobulin to non-peptide antigen in SLE. Furthermore, the studies should also provide a more complete definition of CD1c+B cells, a population of B cells that arises early in the development of the immune system, but whose function remains unknown. Finally, we anticipate that our findings will be useful in establishing new mains of treating autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CD19 TYROSINE MEDIATED SIGNAL TRANSDUCTION IN VIVO Principal Investigator & Institution: Carter, Robert H. Associate Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-JAN-2007 Summary: (provided by applicant): B cells are involved in many autoimmune diseases. CD19 regulates B cell functions in vivo that are important in autoimmunity. Extensive studies in vitro have identified multiple signaling pathways, linked to specific CD19 cytoplasmic tyrosines, that may mediate CD19 function but their relative importance in vivo is unknown. We have developed a system for studying CD19 tyrosine-based signaling in vivo. Mice that are deficient in CD19 lack peritoneal B 1 and marginal zone B cells and respond poorly to T-independent antigens. We reconstituted these functions with an unmutated CD19 transgene, but a construct with mutation of all cytoplasmic tyrosines completely failed to do so, demonstrating the dependence of these B cell functions on CD19 tyrosine signaling. To determine the relevance in vivo of the multiple pathways that have been linked to particular tyrosines and the molecules that bind them in vitro, we produced four transgenes each containing mutations of distinct pairs of homologous CD19 tyrosines. Founder lines for each have been crossed onto the CD19-/background. We initially studied the role of Y482 and Y513, which bind Lyn and phosphatidylinositol 3-kinase (PI3K), and found an absolute requirement for these in all in vivo CD19 functions tested. The likely mechanism is the abrogation of phosphorylation of all CD19 tyrosines by these mutations. This finding establishes that targeting particular CD19 tyrosines can modulate B cell responses in vivo. We propose to: 1) Identify the CD19 structures that control phosphorylation of the molecule, as these
Studies 29
would be targets for global control of CD19 function, 2) Determine the role of binding of cytoplasmic molecules to particular CD19 tyrosines, as these mediate CD19 function, 3) Determine which downstream pathways are controlled by particular CD19 tyrosines in vivo, as these would be identified as regulating important B cell functions, and 4) Determine the role of CD19 tyrosine-based signaling in a mouse model of lupus, to test the hypothesis that targeting specific CD19 tyrosines could be used for therapeutic manipulation of B cells in autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CD4(-) AND CD8(-) T CELLS IN AUTOIMMUNE & NORMAL MICE Principal Investigator & Institution: Strober, Samuel; Professor of Medicine; Medicine; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2003; Project Start 01-MAY-1997; Project End 31-MAR-2007 Summary: (provided by applicant): The object of the proposed studies is to test the hypothesis that the interaction between anti-CD1 reactive NK T cells and marginal zone B cells (IgM(hi) IgD(lo) CD21(hi) CD1(hi)) via CD1 is a critical step in the pathogenesis of lupus in two mouse models; hereditary lupus in NZB/NZW female mice and lupus induced in adoptive BALB/c hosts after the injection of anti-CD1 TCRalpha/beta transgenic T cells. In both models, this interaction is theorized to help activate the marginal zone B cells to secrete autoantibodies, such as anti-dsDNA antibodies, of the pathogenic IgG2a isotype. In vivo and in vitro experiments focus on purifying NK T cells, and on purifying the marginal zone B cells with appropriate mAbs by flow cytometry. We have recently shown that the marginal zone B cells from NZB/NZW mice are the only subset that spontaneously secretes IgM autoantibodies, and is also expressing the IgG2a constant region gene. The sorted NK T cells and non-NK T cells and a variety of B cells subsets from NZB/NZW and transgenic BALB/c mice will be incubated in vitro or transferred to adoptive hosts to determine whether pathogenic autoantibodies are produced resulting in clinical lupus (proteinuria, anti-dsDNA antibodies, increased mortality, etc.) in the adoptive hosts. We will perform immunohistopathological studies to search for the interactions between the critical T and B cells in the marginal zone of the spleen of mice with lupus. In addition, we will attempt to determine patterns of autoantibodies identified in the serum of BALB/c mice injected with anti-CD1 transgenic T cells and compare to NZB/NZW mice. The latter studies will use immunoprecipitation, Western blots, and protein chip arrays. We will assess the impact of anti-CD1 mAb treatment in mice that develop lupus by monitoring disease parameters as well as the spectrum of autoantibodies secreted. Finally, we will attempt to establish a line of NZB mice expressing the green fluorescence protein (GFP) transgene such that transgenic NZB/NZW mice can be used as donors of labeled B cell subsets. The latter cells will be transferred to non-transgenic NZB/NZW hosts to determine their contribution to IgG autoantibody secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CD40 LIGAND IN SYSTEMIC LUPUS ERYTHEMATOSUS Principal Investigator & Institution: Crow, Mary K. Professor; Hospital for Special Surgery 535 E 70Th St New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: Systemic lupus erythematosus (SLE) represents the prototype systemic autoimmune disease, in which the human immune system fails to regulate immune reactivity to chromatin and other well-characterized self antigens. The T helper (Th) cell,
30 Lupus
the central immunoregulatory cell in the normal immune system, mediates the hypergammaglobulinemia and autoantibody formation that result in tissue damage in SLE. CD40 ligand (C40L), a member of the TNF gene family, mediates the Th cell signals that drive B cell activation and differentiation. Several new observations regarding the regulation of CD40L expression on lymphocytes from patients with SLE represent the important preliminary data for the proposed studies: 1) Baseline expression of CD40L is increased in patients with active SLE; 2) Expression of CD40L is prolonged following treatment of SLE T lymphocytes with PMA and ionomycin, a stimulus that bypasses TCR signaling events; 3) Soluble CD40L circulates in SLE and is readily detectable in serum samples from patients. The proposed experiments will investigate potential mechanisms and functional consequences of altered regulation of CD40L expression in SLE. The hypothesis to be pursued is that in SLE, impaired regulation of T cell activation results in excessive Th cell function, autoantibody formation, inflammation, and disease. CD40L is both a marker and mediator of this abnormal T cell help. The specific aims of the project are: I. To Study the Regulation of CD40L Expression in Human T Cells. We will investigate the T cell stimuli required for induction of CD40L mRNA and protein expression, the biochemical pathways that mediate induction of CD40L, the regulation of soluble CD40L production, and the effect of cytokines on expression of cell surface and soluble CD40L. II. To Study the Regulation of CD40L Expression in SLE. We will characterize the baseline activation status of SLE T cells, study the effects of costimulatory molecules and cytokines on induction of CD40L expression in SLE, study transcription and post-transcriptional regulation of CD40L mRNA in SLE, and assess cleavage and clearance of cell surface CD40L in SLE. III. To Study the Functional Properties of Cell Surface and Soluble CD40L in SLE. We will characterize the functional properties of T cell subpopulations expressing CD40L in SLE, and study the functional effects of soluble CD40L on target cell populations. These studies should elucidate disease pathogenesis and identify new targets for therapy in SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELL MEDIATED RENAL INJURY IN LUPUS Principal Investigator & Institution: Kelley, Vicki R. Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 01-FEB-1985; Project End 30-NOV-2002 Summary: The broad objective of this proposal is to test the hypothesis that increased intrarenal macrophage colony stimulating factor (CSF-1) expression is central to the pathogenesis of autoimmune renal disease in MRL-lpr/lpr mice. Using the MRL-lpr/lpr mouse with rapid, uniform, severe and predictable renal disease regulated by the lpr gene we will investigate the importance of CSF-1 in the pathogenesis of lupus nephritis. We propose to test whether the increase in circulating CSF-1 detected in neonatal MRLlpr/lpr mice is contributed by the kidney alone or if other tissues are responsible for elevating serum levels. We will establish whether a molecule(s) in the circulation of MRL-lpr/lpr mice induces intrarenal CSF-1. We will determine whether increased renal expression of CSF-1 recruits macrophages. We will then investigate whether an increased expression of CSF-1 can induce renal disease in mice with normal kidneys including another strain with the lpr gene (C3H- lpr/lpr) and C3H-++ mice or accelerate an indolent, mild nephritis in congenic MRL-++, lacking the lpr gene. We will eliminate CSF-1 by creating a cytokine deficient MRL-lpr/lpr mouse and evaluate the impact on the development of lupus nephritis. In the event that the CSF-1 deficient MRL-lpr/lpr strain does not develop lupus nephritis we will determine if the inability of renal cells to express CSF-1 is responsible for preventing kidney disease. Through the advent of
Studies 31
cellular and molecular techniques we now have the capacity to transfer a cytokine gene using a retroviral vector and establish tubular epithelial (TEC) and mesangial cell lines which can constitutively secrete high levels of a stable cytokine. By implanting these cells under the renal capsule we have created a system to introduce the continuing presence of CSF-1 (or other cytokines) into the kidney. We can then establish if CSF-1 recruits macrophages and determine whether CSF-1 will induce or accelerate renal injury in the MRL-++, C3H-lpr/lpr strains. To definitely establish whether CSF-1 or other cytokines have an enhanced glomerular expression prior to the influx of macrophages, we will isolate and pool individual glomeruli (glom) from MRL-lpr/lpr, congenic, and normal mice at varying ages and quantitate the level of cytokine and macrophages specific marker mRNA using the competitive template polymerase chain reaction. Finally, we will cross the MRL-++ or the C3H- lpr/lpr mice with CSF-1 transgenic mice and select for hybrids with these backgrounds overexpressing macrophage growth factors. In addition, we will eliminate CSF-1 from MRL-lpr/lpr mice by crossing them with the op/+ strain and select for a strain with op/op (producing a non-functional CSF-1) and lpr genes. By increasing or eliminating CSF-1, we will test the impact of this cytokine in promoting renal disease. In addition, we will use the approach of transplanting a kidney into a bilaterally nephrectomized recipient to determine when the MRL-lpr/lpr kidney is responsible for increasing serum CSF-1 and establish if this production is constitutive or is dependent on a stimulus. In addition, we will determine whether a circulating stimulant in the serum of MRL-lpr/lpr mice induces intrarenal CSF-1 and at what age this begins. Finally, we will test whether a kidney unable to express CSF-1 transplanted in the MRL-lpr/lpr mice develops renal injury. Taken together, using several novel approaches we will be able to clarify the importance of CSF-1 in the pathogenesis of lupus nephritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHANGES ERYTHEMATOSUS
IN
EBV
INFECTION
IN
SYSTEMIC
LUPUS
Principal Investigator & Institution: Gross, Andrew J. Microbiology and Immunology; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): We will use the human herpesvirus, Epstein-Barr virus (EBV), to probe immune dysfunction in systemic lupus erythematosus (SLE) by studying changes in EBV latent infection in these patients. EBV establishes lifelong infection in >90% of humans. In healthy individuals this is a tightly regulated process, which is evident in the blood, where: the virus is only carried by memory B cells; the viral load is stable over long periods of time; and there is little or no viral gene expression. We have preliminary data that indicates EBV latent infection is disrupted in patients with SLE. First, there are very high viral loads in the blood of these patients. Previous work by our laboratory showed that treating organ transplant recipients with immunosuppressive medications leads to similarly elevated viral loads. However, analysis of the preliminary data indicates that these high loads of EBV in the blood of patients with SLE cannot be accounted for by treatment with immunosuppressive agents. Furthermore, the increase in the viral load is related to the presence of flares of SLE; when patients are symptomatic and immune deregulation is at its maximum, the viral load increases. Second, a latency gene of the virus, LMP1, is atypically expressed in the blood of these patients. We hypothesize that there are two aspects of the immune dysfunction in SLE that could disrupt EBV infection. First, defects in cytotoxic lymphocyte (CTL) function can result in increases in viral load, but not affect other
32 Lupus
aspects of the infection. Second, defects in the cells that harbor the virus, memory B cells, could lead to the appearance of atypical states of viral infection in the blood and/or result in an increase in viral loads in the blood. In this proposal we will assess the relative contributions of these two mechanisms. We will evaluate 1) whether there are defects in CTL function in patients with SLE; 2) whether there are alterations in EBV infection in the blood of patients with SLE, such as infection of other B cell types and expression of EBV genes; and 3) changes in CTL function and EBV infection are affected by SLE disease activity. These studies will provide new insight into the immune dysfunction in SLE and shed light on the cause of this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHARACTERIZATION OF SLE SUSCEPTIBILITY LOCI ON MOUSE CHROMOSOME 4 Principal Investigator & Institution: Morel, Laurence; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001 Summary: Sle2 on mouse chromosome 4 is a strong recessive locus associated with lupus nephritis in the NZM2410 model. Other groups have identify other SLEassociated loci in the centromeric half of this chromosome. Congenic analysis has showed that Sle2 is associated with B cell hyperactivity resulting in producing of polyclonal IgM antibodies, in vivo and in vitro hyper-responsiveness, increased B7.2 expression, and enlargement of the Bl1 population. Characterization of polycongenic strains combining Sle1, -2. and -3 has shown that Sle2 is necessary for full disease expression, and that, in combination of Sle3, Sle2 results in highly penetrant nonpathogenic hyaline and mesangial renal lesions that might constitute an accelerating factor for lupus nephritis. Using the congenic dissection approach, and following the steps that we are following in the functional and genetic dissection of the role of telomeric chromosome 4 in SLE pathogenesis. To achieve this goal, we have produced a series of 10 sub-congenic strains covering the area. We will use these strains in two specific aims: 1) We will assess whether the various phenotypes associated with Sle2 result from a single or several loci and generate a high resolution genetic map of these loci. The immunological defects and gene expression profile associated with each of these loci will be established. 2) We will determine the contribution of these loci to SLE pathogenesis by combining the corresponding sub-intervals to either Sle3 or the Sle1/Sle3 combination to reconstitute the Sle2/Sle3 or Sle1/Sle2/Sle3 immunopathology, respectively. Preliminary results indicate that the elevated B7.2 expression, but not increased Bl1 compartment, is associated with increased pathogenicity. These experiments are a necessary step towards the identification of the SLE-susceptibility genes on mouse chromosome 4. A high resolution genetic map that leads to the physical map and ultimate cloning of the gene cannot be constructed without a solid evaluation of the number of loci and their associated defects. Finally, the understanding of their relative contribution to the disease process will establish priorities for gene identification. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHROMOSOME 1 REGIONS LINKED TO SLE IN MULTIPLEX FAMILIES Principal Investigator & Institution: Tsao, Betty P. Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024
Studies 33
Timing: Fiscal Year 2002; Project Start 30-SEP-1996; Project End 31-MAR-2007 Summary: (provided by the applicant): Systemic lupus erythematosus (SLE) is a hetereogeneous autoimmune disease characterized by a plethora of immunopathologic manifestations including the production of autoantibodies to various nuclear components. Genetic predisposition clearly plays an important role in risk for developing SLE, however, many remain elusive. Genome scans have mapped many SLE susceptibility loci in both murine and human SLE. One genomic region on the distal end of mouse chromosome 1 and its syntenic human counterpart 1q23-44 has shown strong evidence to harbor SLE susceptibility genes in multiple independent genome scans of both mice and humans. We have observed evidence for linkage to SLE at 1q23 and 1q4142 in our cohort of affected sibpair families. In this application, we propose to identify genetic polymorphisms within 1q21-44 that are associated with SLE or SLE subsets in our cohort, and to explore if the same or functionally related genes contribute to syntenic conservation in susceptibility intervals between mice and humans. Our aims are as follows: 1) To continue family ascertainment for an additional 150 SLE multiplex families and an additional 500 simplex families and to assess familiality of SLE manifestations. The enlarged multiplex families will allow more samples in each stratified subset (by ethnicity, SLE-manifestations, or age of disease-onset), hence greater statistical power to localize the linked interval. The enlarged simplex families will allow greater statistical power for association studies in each ethnic group. Familial SLE manifestations will be used in stratification of our family collection to reduce genetic heterogeneity in subsequent linkage and association studies. 2) To perform a targeted genome scan of chromosome 1q21-44 and to narrow the intervals linked to SLE susceptibility. 3) To perform linkage disequilibrium mapping of the narrowed genomic intervals to eventually localize genetic polymorphisms associated with SLE susceptibility. 4) To assess human homologues of candidate murine SLE susceptibility genes (Sle1d, Nba2, and Lbw7) for evidence of association in our cohort. The identification of SLE susceptibility genes can reveal underlying mechanisms in the pathogenesis of autoimmunity and provide potential targets for disease management. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHROMOSOME 6P AND DEVELOPMENTAL DEFECTS Principal Investigator & Institution: Rosen, Fred S. Professor of Pediatrics; Cbr Institute for Biomedical Research 800 Huntington Ave Boston, MA 02115 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: Systemic lupus erythematosus (SLE) is an autoimmune disorder which affects over 200,000 women in the USA and it is characterized by anti-nuclear antibodies and a high incidence of glomerulonephritis. A major risk factor for SLE is deficiency in early classical pathway complement components C1, C2 or C4. This association presents a paradox because it is not expected that an immune deficiency would result in an autoimmune disease. One explanation is that early complement is involved in maintenance of B cell tolerance and in its absence, self-reactive B cells accumulate in the periphery where they potentially may be activated. The goal of this proposal is to test this hypothesis and it is divided into 3 specific aims: (i) Test the hypothesis that early classical pathway complement components C1, C4 and C3 are directly involved in negative selection of self-reactive B lymphocytes. The approach used in this aim is to breed mice deficient in C1, C4, or C3 with two well established immunoglobulin transgenic models (anti-HEL and anti-dsDNA) and determine if complement is essential in B cell anergy. (ii) The second aim will test the hypothesis that deficiency in classical pathway complement results in increased severity of disease in a well defined mouse
34 Lupus
model of lupus, i.e. lpr strain. The advantage of this aim is that it will examine the importance of early complement in the autoimmune response to natural lupus antigens such as dsDNA and nuclear proteins. (iii) The third aim will test the hypothesis that impaired self-tolerance in C4null mice can be rescued by protein replacement or gene therapy and if so compare C4A and C4B isotypes. It will also examine the mechanism of C4 in B cell tolerance using a fusion protein of C4d linked to sHEL antigen to uncouple solubilization of immune complexes from targeting of antigen to the lymphoid compartment via C4d. This aim is important as it will establish the feasibility of protein or gene therapy in lupus and clarify our understanding of B cell tolerance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPLEMENT C4 AND HLA CLASS III GENES IN HUMAN SLE Principal Investigator & Institution: Yu, Chack Y. Associate Professor; Ohio State University 1800 Cannon Dr, Rm 1210 Columbus, OH 43210 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAR-2006 Summary: Complement proteins are essential in the dissolution of immune complexes (IC). The circulation of pathogenic IC is an etiologic factor for kidney and autoimmune disease. Systemic lupus erythematosus (SLE) is multi-factorial disease with complex genetic trait and diverse clinical manifestations. Lupus nephritis (SLE-N) is a severe form of the disease. Specifically, this proposal seeks to determine the roles of complement component C4, which has an amazing degree of variations in the quantities and qualities of the genes and proteins present in each individual, in the disease etiology of SLE and SLE-N. The quantitative variations include the number of the C4A and C4B genes present that may determine the levels of proteins expressed in patients and in normals. We hypothesize that over-expression of C4 (C4A, C4B or both), underexpression of C4 (C4A or C4B or both), and malfunction of C4A or C4B contribute to the etiological processes of SLE and SLE-N. In other words, the pathogenesis of SLE may be related to the C4 gene dosage (number of C4 genes), C4 gene types (long and short C4 genes), and C4 protein functions (C4A and C4B isotypes and allotypes). Over-expression of C4 may aggravate the disease by directly promoting the local activation of the complement system that causes tissue injuries. Under-expression of malfunction of the CR would lead to impairment in the dissolution of IC. Specific techniques to determine the qualitative and quantitative variations of the RCCX constituents including complement C4A and C4B have been established by our laboratory. Many novel genes have been discovered in the MHC class III region. These breakthroughs allow the following Specific Aims to be addressed: I) To determine the RCCX modular variations in SLE, SLE-N and normals; II) To determine the molecular bases of C4A and C4B deficiencies in SLE-SLE-N and normals; IV) To investigate the molecular genetics of the MHC class III genes in SLE, SLE-N and normals. The study population include 250 individuals with SLE-N, and equal numbers of SLE patients with non- renal involvement, affected family based controls and case matched controls. The results of this proposal will directly influence the philosophy on the treatment (and possibly cure) of SLE and SLE-N. It may have enormous impact on the medicare of the SLE and other rheumatic disease patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COMPLEMENT, CARDIOVASCULAR DISEASE, AND SLE Principal Investigator & Institution: Ahearn, Joseph M. Associate Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260
Studies 35
Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Inflammation is now recognized as a critical process in the development and rupture of atherosclerotic plaques, and in the morbidity and mortality that result from cardiovascular disease. Recent studies have also suggested that this process may be accelerated and exaggerated in patients with systemic lupus erythematosus. We have recently established a research program focused on vascular biology and pathology, with a focus on lupus as a model of accelerated atherosclerosis. The stimulus for these investigations was a recent surprising observation by Manzi and colleagues who demonstrated a strong linear association between elevated serum levels of C3 and C4 and aortic stiffness in premenopausal women with SLE. Whereas decreased serum levels of C3 and C4 have traditionally been used to monitor disease activity in patients with SLE, association of elevated serum levels of serum complement components with any disease process is unprecedented. This observation led us to investigate the potential role(s) for complement C3 and C4 in the immunopathogenesis of cardiovascular disease in SLE. Vascular imaging studies led to several intriguing and unexpected observations that will be further explored here. First, we discovered that complement components C3 and C4 are present in several distinct patterns within the arterial walls of both humans and mice. Specifically, proteolytic fragments of C3 and C4 co-localize with, and may be covalently bound to, elastin within the arterial wall. This entirely unexpected observation suggested that complement deposition within the arterial wall may increase vascular stiffness, an early event in atherosclerosis, through direct interference with elastic fiber flexibility. Second, we observed aggregates of complement deposition within the vessel wall, the site at which plaque formation is now known to initiate. Third, we demonstrated that complement components are specifically present within the vasculature of mice with lupus-like syndromes as compared with controls. These observations, together with those of Manzi and colleagues, have led to the following specific aims that are based on our central hypothesis that the complement system may influence vascular stiffness and contribute significantly to the atherosclerotic process by directly reducing vascular elasticity within the arterial wall. The long-term goal of this proposal is to perform an initial characterization of the role of the complement system in atherosclerosis, using normal and abnormal human and mouse vascular systems. Specific Aim 1 is to characterize the spatial and temporal localization of complement proteins C3 and C4 within the arterial wall. Specific Aim 2 is to characterize the distribution of complement C3 and C4 within the arterial tree. Specific Aim 3 is to determine the capacity of complement C3 and C4 within the arterial wall to increase arterial stiffness. These studies will represent the first rigorous investigation of the role of the complement system in atherosclerosis, using SLE as a model of accelerated coronary vascular disease. Ultimately, the data generated by the proposed studies should identify therapeutic targets in SLE and in atherosclerosis in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--CELL SCIENCES AND IMMUNOCHEMISTRY Principal Investigator & Institution: Gaskin, Felicia; Charlottesville Box 400195 Charlottesville, VA 22904
University
of
Virginia
Timing: Fiscal Year 2001 Summary: The Cell Sciences and Immunochemistry Core (CIC) is an integral part of the SLE SCOR Center, providing services to the four principal investigators on projects that rely on the following laboratory support. First, routine histology and electron microscopy studies and their interpretations. Second, tissue and cellular localization of
36 Lupus
antigenic molecules by immunohistology, and messenger RNA (mRNA) by in situ hybridization. Third, acquisition and management of human and murine recombinant proteins and peptide libraries for the "lupus antigens" including Ro60, Ro52, La, Sm, calreticulin, U1-70 RNAP, dsDNA and phospholipids. Fourth acquisition and management of a library of essential monoclonal Ab and cDNA probes for Ag localization and flow cytometry, as well as B cell hybridomas generating sufficient monoclonal Ab for in vivo experiments. Fifth, quantitation and isotype determination of human and murine autoAb by immunoprecipitation and ELISA. Sixth, quantitation of murine cytokines by ELISA. The CIC will function, in collaboration with the project investigators, in experiments that: 1) analyze autoAb responses to the "lupus Ag" and their overlapping peptides, 2) require peptides for mapping their T and B cell epitopes, 3) evaluate the immunopathologic end points including the detection and semiquantitation glomerulonephritis, sialoadenitis and diseases affecting other organs that result from autoimmune response to the lupus Ag, 4) evaluate the quality of the autoimmune response with respect to the specificity and Ig isotype of the autoAb and the nature of the cytokines produces by peptide specific T cells. In summary, the CIC will support the research project of the SLE SCOR by providing common reagents and by conducting several essential and common techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--METHODOLOGY AND DATA MANAGEMENT Principal Investigator & Institution: Chang, Roland W.; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2001 Summary: The Methodology and Data Management Core is critically important to the success of this MAMDC and its EEHSR Component in particular. The centralized availability of expertise in database and study form construction; data entry, monitoring, and retrieval, and the various analytic techniques used to test hypotheses and control for potential confounders are essential resources for all investigators. The Core has assisted educators, epidemiologists, and health services researchers from several divisions and departments in studying a wide variety of disease and demographic groups including systemic lupus erythematosus, osteoarthritis, juvenile dermatomyositis (JDMS), rheumatoid arthritis, and the elderly. Core resources have been used efficiently because of the economies of scale in addition to excellent coordination with the EEHSR component. Recognizing that newer analytic techniques have become available and more accepted and that this proposal represents an expansion of our work in clinical epidemiology and health services research, this proposed Core is both larger to support a greater volume of work and broader t utilize these new analytic techniques. As a result of the Executive Committee's decision to emphasize longitudinal and cost-effectiveness research, experts in advanced statistical techniques (generalized estimating equation (GEE), classification and regression trees (CART), econometric approaches to controlling selection bias, meta-analysis), economics, and decision analysis (stochastic tree modeling, continuous- risk utility assessment) have been recruited as Core co-investigators. Clinical Epidemiology has also been formally included within the Core structure. The Core will support the four EEHSR proposals in this grant application and the funded activities of the JDMS registry and Children's Memorial Hospital. It will continue to contribute to the MAMDC research environment by providing data management and methodologic assistance to investigators who engage in arthritis related research. The institution of a EEHSR/Core research conference and enhanced viability and support for health services research on
Studies 37
Northwestern University's Chicago Campus will further heighten the Core's influence on the environment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--MOUSE GENETIC Principal Investigator & Institution: Brown, Michael D. Assistant Professor; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2003 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) is a systemic autoimmune disease process contributed by multiple genes in humans and mouse models. The usefulness of the mouse as a model organism for studies of factors that contribute to pathogenesis has been well accepted. To date, as many as 12 distinct loci have been implicated in mouse lupus, but strong genetic linkages have been assigned to chromosomes 1, 4, 7 and 17. Newly available genetic tools are transforming studies of autoimmune disease in mouse models and have the potential to support rational exploration of complex physiological pathways and genetic traits. Congenic mice are especially useful in this regard since they are amenable to the study of the effects of single genes or multiple tightly linked genes in genetically controlled experiments, thus enabling directed and rational approaches toward the study of multigenic traits. Moreover, congenic mice and recombinant congenic mice derived from them, provide the foundation for genetic mapping and positional gene cloning strategies. Ultimately, information and resources gained from investigation of mouse models may be exploited to identify and characterize human genes that contribute to autoimmune disease. In order to make these genetic tools available to the members of the SCOR, we have established the Mouse Genetics Core (MGC). The primary role of the Mouse Genetics Core is to maintain extant mouse models and to develop and maintain novel mouse models for studies of autoimmune disease in well characterized and appropriate genetic backgrounds as needed by SCOR Principal Investigators serving all four SCOR projects. Novel congenic, recombinant congenic and gene targeted mice will be generated using a "speed congenic" strategy utilizing genome-wide microsatellite screening sets that others and we have previously characterized. In particular, the MGC will serve as a breeding unit and genetic analysis facility for efficient and controlled propagation and selection of specified genetic traits or mutant genes in mice. Genetic characterization will include genotyping, microsatellite linkage, DNA sequencing, and gene expression analyses. In addition, the MGC will serve as an educational resource, providing information and training for all aspects of mouse breeding and handling and genetic characterization for SCOR Investigators and their laboratory personnel. Hence, the MGC will service the needs of the SCOR Investigators by providing an operational and centralized mouse core facility to maintain and develop the necessary mouse models for continued SLE investigation and will encourage expansion of biochemical and physiological studies from cell culture systems into whole animal models, facilitating linkage of basic research with preclinical studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COSTIMULARTORY ERYTHEMATOSUS
ANTAGONISTS
/SYSTEMIC
LUPUS
Principal Investigator & Institution: Davidson, Anne; Associate Professor; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007
38 Lupus
Summary: Although, the lifespan with SLE has improved considerably over the last several decades, safer and more effective therapies as needed. The discovery of costimulatory molecules has led to the consideration of new therapies for SLE aimed at decreasing activation thresholds of both B and T cells. Use of costimulatory blocking agents in appropriate combinations may allow us to treat SLE flares with short term regimens, so as to avoid the morbidity associated with long term immunosuppressive therapy. In Aim 1 of this proposal we will develop modulators of two newly discovered members of the B7/CD28 and TNF/TNFR families and test them in prevention and remission induction studies in SLE prone mice in combination with a knock effective agent, CTLA4Ig. The CD28 like molecule ICOS that costimulates activated T cells and secondary B cell responses will be blocked with a soluble murine ICOS-IgG2a fusion. The CD40L like molecule BAFF, that costimulates both naive B cell development and germinal center formation, will be blocked with either a dimeric or pentameric fusion protein of its receptor TACI. In Aim 2 we propose to understand at which stage of C cell development these new agents are effective by using novel methods of isolating populations of naive and antigen activated autoreactive B cells that can be studied using a variety of immunochemical and molecular techniques. In Aim 3 we will determine the effect of CTLA4Ig with and without addition of ICOS or BAFF blockade on two populations of T cells that may influence disease progression- memory and NK T cells. The mechanistic studies proposed in this application will have direct clinical relevance because they permit us to understand the effect of showing signs of disease activity. As immune modulating agents begin to enter early clinical trials in humans, understanding their short and long term effects on the B cell repertoire and B cell activation in the autoimmune host is critically important. Analysis of the pathways that are inactivated by these new reagents will pave the way towards development of more specific targeted therapy for SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CR2 AS A MURINE LUPUS SUSCEPTIBILITY GENE Principal Investigator & Institution: Boackle, Susan A. Assistant Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): The major murine systemic lupus erythematosus (SLE) susceptibility locus, Sle1, corresponds to 3 loci independently affecting loss of tolerance to chromatin in the NZM2410 mouse. The congenic interval corresponding to Sle1c, derived from NZW, contains Cr2, which encodes complement receptors I and 2 (CR1/CR2, CD35/CD21). CR1/CR2 deficiency has been associated with autoimmune disease in both humans and in animal models. A structural difference in a critical ligand-binding domain has recently been identified in Sle1c CR1/CR2 which results in significant impairment in receptor function. These results strongly support the role of Cr2 as a disease susceptibility gene in the Sle1c interval. The project outlined in this proposal will be directed towards characterizing the role of NZW CR2 in the NZM2410 mouse model for lupus. The specific aims are to prove that CR2 is the lupus susceptibility gene in the NZM2410 Sle1c interval, to identify the structural domains in NZW CR2 that are critical in loss of tolerance, and to determine the mechanisms by which NZW CR2 results in loss of tolerance. Proof that CR2 is the lupus susceptibility gene in the Sle1c locus will be provided by demonstrating that the Sle1c phenotypes resolve in the presence of normal gene products. Recombinant strains that contain narrowed intervals containing Cr2 will be assessed to ensure that CR2 dysfunction
Studies 39
continues to track with autoimmune disease, The critical receptor domains that result in the autoimmune phenotypes will be determined, using both CR2-deficient cell lines transfected with recombinant proteins as well as B cells from BAC transgenic mice that express various forms of the polymorphic NZW CR2. Finally, the mechanisms by which the altered NZW CR2 allele results in loss of B cell tolerance will be characterized using the 3-83 and HEL models for B cell tolerance. These studies will clarify the specific functions of CR2, impaired in the NZM2410 mouse model, that may impact on the development of autoimmune disease and thus be important targets for therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYCLOOXYGENASE/NUCLEOBINDIN INTERACTION Principal Investigator & Institution: Simmons, Daniel L. Chemistry and Biochemistry; Brigham Young University A-261 Asb Provo, UT 846021231 Timing: Fiscal Year 2001; Project Start 01-SEP-1999; Project End 30-JUN-2003 Summary: Cyclooxygenases (COXs) catalyze the rate-limiting step in the synthesis of prostaglandins, prostacyclin, and thromboxanes. Derived from arachidonate, these biomediators act as local hormones affecting inflammation, pain, and a host of other physiological processes in the cell and organism. There are presently two known COXs. COX-1 is typically expressed constitutively like a housekeeping protein. COX-2, in contrast, is highly inducible by growth factors and hormones. Many cells contain both COX-1 and COX-2. In these cells arachidonate is delivered selectively by an unknown mechanism to COX-2 following mitogen stimulation. Also, COX-1 and COX-2 can have very different sensitivities to NSAIDs in vivo than in their purified states in vitro. These data suggest that, in spite of the colocalization of COX-1 and COX-2 to the lumen of the endoplasmic reticulum and nuclear envelope, unknown factors confer unique, isoenzyme-specific properties on these structurally and enzymatically similar proteins. While in search of proteins which might confer these properties, our laboratory determined that the calcium binding protein, nucleobindin (Nuc), associates with cyclooxygenases in the yeast 2-hybrid system and in other in vitro and in vivo assays. Extracellular release of Nuc into the blood stream has been associated with systemic lupus erythematosus-like symptoms in mice. Indeed, Nuc was first isolated as a protein responsible for the generation of anti-DNA antibodies in a genetic mouse model for lupus. Moreover, injection of purified Nuc into normal mice elicits some of the symptoms of lupus. Similar to COXs, Nuc is widely expressed in tissues; however, its function in these tissues is unknown. Our hypothesis is that Nuc functions in COX/Nuc complexes to regulate prostaglandin synthesis and that COXs may function in the release of Nuc in autoimmune disorders. In these proposed studies, Nuc and COX isoenzymes will be co-expressed at high levels in insect cells and the enzymatic and physical properties of COX/Nuc complexes relative to unbound COX- 1 and COX-2 will be studied. Pharmacologically important aspects to be analyzed include the effect of Nuc on the rate of prostaglandin synthesis and on the inhibitory action of non-steroidal antiinflammatory drugs (NSAIDs). Additionally, a new variant of Nuc expressed in fibroblasts that lacks 33 amino acids in its COX binding domain will be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CYTOKINES AS PREDICTORS OF FLARE IN SLE Principal Investigator & Institution: Rus, Violeta; Medicine; University of Maryland Balt Prof School Baltimore, MD 21201
40 Lupus
Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: The candidate, Violeta Rus, is a rheumatology fellow and future Clinical Instructor at the University of Maryland Medical School, where she is developing a career in clinical research in lupus. The proposed work draws on her bench-research experience on the role of cytokines in a murine models of lupus, and requests support for a Mentored Patient-Oriented Career Development Award to acquire new expertise in the science of clinical investigation in order to be able to translate new biomedical advances to the bed-side. The candidate will work under the mentorship of Dr. Charles S. Via and Marc C. Hochberg in the superb research environment, resources and opportunities for career development at the University of Maryland Medical School. The candidate's immediate goals are to obtain the training necessary to become a successful, independent clinical investigator able to pursue high quality hypothesis-driven disease oriented research. The proposal is an outgrowth of the PIs previous work in a murine model of lupus where she identified the role of several cytokines important in driving autoantibody production. The present study will define the cytokine pattern in active and inactive lupus patients and determine whether changes in cytokine levels will predict future flares. Hypothesis: High levels of B cell stimulatory cytokines IL-10 and IL-6 and low or variable levels of IFN-g and TNF-a will correlate with disease activity in lupus patients and precede disease flare. Conversely, reciprocal changes of these cytokines will accompany or precede disease remission. Specific Aim 1) Determine in a cross sectional study whether disease activity is correlated with altered serum or mRNA levels of IL-10, IL-6, IFN-g and TNF-a. Cytokines will be measured in serum specimens by ELISA and in peripheral blood mononuclear cells mRNA by semiquantitative RTPCR. Specific Aim 2) Determine in a longitudinal study whether alterations in these cytokines precede or accompany disease flare and post-flare improvement. Samples of serum and mRNA from 50 patients followed longitudinally will be tested every 3 month in stable patients, biweekly during flares and monthly until remission. For both aims, flares will be defined using SLEDAI and Physician Global Assessment scores. Statistical analysis using exploratory analyses and regression models will be used. The proposed research will have high relevance to our understanding of the role of cytokines in inducing flares and remissions in SLE, assess their predictive value for future flares, and develop a rationale for future cytokine-based therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DELINEATION PATHOGENESIS
OF
GENETIC
PATHWAYS
TO
LUPUS
Principal Investigator & Institution: Liu, Kui; Microbiology; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: (provided by the applicant): Systemic lupus erythematosus (SLE) is characterized by the presence of anti-nuclear antibodies (ANA) directed against naked DNA and entire nucleosomes. Development of congenic mouse models carrying lupus susceptibility gene intervals has provided powerful tools for studying the mechanism of lupus pathogenesis. Sle1 mediates the loss of tolerance to nuclear antigens and the initiation of autoimmunity. Our recent study demonstrated that Sle1 mediates the abnormal expression of several genes, including the c-myc protooncogene, that control B-cell activation and proliferation. We hypothesize that autoreactive B-cells are generated from B-cell populations that have aberrant c-myc expression. We propose to identify the mechanisms leading to the aberrant c-myc expression and to characterize the B-cell populations that have aberrant c-myc expression in B6.Sle1 mice. We also
Studies 41
propose to use powerful, microarray-based approaches to identify the molecular mechanisms by which Sle1 and S1e3 interact to cause lupus. Furthermore, we propose to identify lupus susceptibility gene(s) in the S1e3 interval using fine mapping in combination with functional genomics. By identifying the lupus susceptibility genes and the molecules involved in the pathogenesis, we can select candidate therapeutic targets for curing lupus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYSREGULATION OF THE IMMUNE SYSTEM IN AUTOIMMUNITY Principal Investigator & Institution: Flavell, Richard A. Professor and Chairman; Immunobiology; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 01-SEP-1994; Project End 29-SEP-2002 Summary: The goal of this program is to understand the regulation and dysregulation of the immune system in autoimmunity. The program involves collaborative interaction between members of three Departments, and is organized into four projects supported by three Core facilities. Expertise in the field of immunology, molecular biology, and biochemistry will focus on the vents that initiate and sustain autoimmune responses, and the regulatory processes. which contain autoimmunity. We will address the following questions. What are the requirements to initiate autoimmune responses? Are autoimmune responses regulated, and if so, by what mechanisms? Does immune regulation contain autoimmune responses under normal circumstances? Finally, do sustained autoimmune responses remain chronic because they diversity from a single initiating response to responses to other autoantigens from the same tissue? These questions will be addressed by collaborative interactions between the Principal Investigators of these projects, which are as follows: (1)R.A. Flavell- Using transgenic mice expressing a T cell receptor specific for myelin basic protein (MPB) and gene targeted mice lacing L- selectin or E- and P-selectin, the role of selectins in the development of EAE will be determined. The requirement of selectins for the development of disease, as well as the mechanisms which underlie this requirement will be determined, focusing on the cell types which must express L-selectin, the role of selectins in the entry of leukocytes into the CNS and the potential role of selectins within the CNS. (2) C.A. Janeway Jr.- This project will investigate four aspects of the regulation of experimental allergic encephalomyelitis (EAE): Why are mice lacking B cells unable to fully resolve their disease; why does the inability to form cells with other receptors lead to spontaneous disease in mice transgenic for a TCR that recognizes myelin; why do mice cells with other receptors lead to spontaneous disease in mice transgenic for a TCR that recognizes myelin; why do mice with the same receptor who are heterozygous for gld get spontaneous disease; and what is the role of L- selectin in EAE, in collaboration with project 1. (3) M.J. Shlomchik- Transgenic mouse models will be used to study the regulation of B cells expressing a disease-related autoantibody, rheumatoid factor (RF), in normal and autoimmune mice. In contrast to some other autoantibody models, RF B cells from these transgenics are competent to initiate an immune response. Thus, studies will focus on how RF B cells are regulated after Ag stimulation in normal mice and propagated in autoimmune mice, and what prevents chronic autoimmunity in RF transgenic mice. (4) M.J. Mamula, PI- This project will examine the role of self-peptides in the initiation and perpetuation of both Band T cell autoimmunity in models of systemic lupus erythematosus (SLE) and multiple sclerosis (EAE). The role of B cells as autoantigen in models of systemic lupus erythematosus (SLE) and multiple sclerosis (EAE). The role of B cells as autoantigen presenting cells will be examined with relevance to mechanisms that lead to epitope spreading in autoimmunity. Finally, this
42 Lupus
work will study a novel post-translational peptide modification that arises naturally in cells and confers immunity to self peptides. These four projects will be supported by an administrative core to coordinate the project as a whole, a genetically modified mouse core to provide gene targeted and transgenic rodents essential to most of these studies, and a FACS core, to allow us to separate cells for analysis and to analyze cells in all of these projects. The program is coordinated by frequent meetings of the program faculty bringing together these diverse approaches to address a common goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ECTOPIC GERMINAL CENTER REACTION IN SYSTEMIC LUPUS Principal Investigator & Institution: Pascual, Maria V. Pediatrics; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the Investigator's abstract): Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ involvement and widespread immunologic abnormalities, the most relevant of which are hypergammaglobulinemia, immune complex formation, and complement system activation. Highly specific autoantigen-driven responses, particularly those directed at protein and nucleic acid components of intracytoplasmic and intranuclear particles, are characteristic of SLE patients. At the peak of disease activity and antibody secretion, however, SLE patients are known to display peripheral blood lymphopenia. The investigator's laboratory has previously described methods to isolate human peripheral B cell subpopulations. Now they show that the peripheral blood B cells of children with SLE differ from healthy adults and children. In particular, the conventional recirculating naive B cell pool is decreased in children with SLE, while B cells with pre-germinal center phenotype are expanded. Consistent with this information, genes restricted to the germinal center (GC) reaction can be amplified from SLE peripheral B cells. Additionally, a cell population that co-purifies with B cells but lacks the pan-B cell markers CD19 and CD20 is expanded in these patients. This population is composed of a CD79a+ B cell subset, and a CD79a- (dendritic cell?) subset. These data lead the investigators to propose that an ectopic and accelerated GC reaction takes place in SLE. The experiments described below are designed to test their hypothesis and to gain understanding of the nature of B cell alteration(s) in SLE. The aims of the current application are: 1. To further demonstrate that the IgD+ CD38+ population + _ expanded in the blood of SLE patients corresponds to pre-GC cells. 2. To + _ characterize the phenotype and function of the recirculating B cell subpopulation(s) expressing surface CD40-L in SLE blood. 3. To identify the + _ nature and function of the SLE-restricted CD19- CD20- cell populations that co-purify with B cells. 4. To determine the clinical relevance of the + _ accumulation f IgD+ CD38+ B cells and/or CD19- CD20cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ELICITATION OF HIV SPECIFIC CATALYSTIC IMMUNITY Principal Investigator & Institution: Paul, Sudhir; Professor; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001 Summary: In view of the enhanced antigen neutralizing capability imparted by the catalytic function, we propose to isolate antibodies (Abs) for passive immunotherapy of HIV-1. This goal has become feasible because of the recent acquisition of the following
Studies 43
information: a subset of Abs expresses peptidase activity; synthesis of peptidase Abs, including gp120 cleaving Abs incresed in lupus mice; the peptidase activity is encoded by a germline gene encoding the variable (V) region of the light chain subunit; and, the catalytic site is structurally similar to the active sites found in non-Ab serine proteases. In Aim 1, the specificity of the gp120 cleaving Abs in lupus mice will be enhanced by immunization with gp120, a B cell epitope derived from the CD4 binding site of gp120, and if needed, intact HIV-1 particles. Recombinant Fv constructs with peptidase activity will be selected from phage display libraries (constructed by Core B) using gp120 analogs designed to bind covalently to the serine protease-like site found in certain Ab light chains (covalently reactive analogs, CRAs). The CRAs to be employed include derivatives of the whole gp120 molecule and the gp120 epitope. The essential features of the CRAs include: the presence of an electrophilic ester group reactive with nucelophilic Ser residues, a phosphonate structure mimicking the tetrahedral transition structure, a basic flanking residue reactive with the germline peptidase sites, and additional flanking residues derived from gp120 to permit high affinity gp120 recognition by the Abs. In Aim 2, the CRAs will be employed as immunogens to permit the selective recruitment and somatic maturation of the catalyst gene(s) for synthesis of gp120cleaving Abs. Improvements in the catalytic turnover are predicted over the course of clonal selection because superior CRA binders are likely to be superior transition state stabilizers. This will be evident as increased binding of the Abs to the CRAs relative to the unmodified gp120. As in aim 1, the best catalysts will be isolated from Fv phage display libraries using CRA selections. Cleavage of the gp120 B cell epitope, monomer gp120 in solution, and native gp120 expressed on the HIV surface will be studied by electrophoresis, HPLC and radioassay methods. The catalytic Ab responses in autoimmune and non-autoimmune mice will be compared to determine whether the regulatory factors limiting catalytic Ab synthesis by the healthy immune system are surmounted by the CRA immunizations. In vitro HIV-1 infectivity studies will be carrie dout by Core C to compare the HIV neutralizing activity of catalytic and noncatalytic Abs. The desired result from these studies is that we will have in hand catalytically efficient Fv constructs derived from autoimmune mice with the capability of specifically cleaving gp120 and potently neutralizing the infectivity of HIV-1. In addition, if the gp120 CRAs provoke a catalytic Ab response in non-autoimmune mice, these reagents can be considered as prototypes for a prophylactic vaccine capable of eliciting catalytic immunity to HIV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF CARDIOVASCULAR DISEASE IN LUPUS WOMEN Principal Investigator & Institution: Manzi, Susan M. Associate Professor of Medicine and Epid; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001 Summary: Cardiovascular event rates in women with lupus represent a 5 to 10 fold increase as compared to population-based studies of normal women. The pathogenesis for premature atherosclerosis in women with lupus is likely multifactorial. The first aim of this study is to estimate the prevalence of clinical and sub-clinical atherosclerosis in women with lupus. The second aim is to determine the association between atherosclerosis and markers of inflammation in women with lupus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
44 Lupus
•
Project Title: EPIDEMIOLOGY OF OSTEOPOROSIS IN WOMEN WITH LUPUS MAMDC PROJECT Principal Investigator & Institution: Ramsey-Goldman, Rosalind; Northwestern University Office of Sponsored Programs Chicago, IL 60611
Professor;
Timing: Fiscal Year 2001 Summary: The specific aims to be addressed in this study are: 1) To estimate the differences in bone mineral density (BMD) at the hip and lumbar spine between 128 Caucasian and 128 African-American women with lupus and a comparable control group matched by age, race, and menopause status; 2) To determine the association of lupus risk factors with low BMD in women with lupus, after controlling for traditional risk factors for low BMD; 3) To follow the subjects entered in the cross-sectional study over a two year period in order to estimate the difference in the rate of bone loss at the hip and lumbar spine between women with lupus and a comparable control group matched by age, race, and menopause status; and 4) To determine the association of lupus risk factors with increased rates of bone loss in women with lupus, after controlling for traditional risk factors for low BMD. The hypotheses to be examined in this study are: 1a) Women with lupus have lower BMD at the hip and spine than matched controls; 1b) the negative effect of lupus on bone mineral density at the hip and spine is greater in Caucasian than in African-American women; 2a) Traditional risk factors for low BMD (nulliparty and menopause status, irregular menstrual cycles or premature menopause, avoidance of oral contraceptives and/or hormone replacement therapy, lower physical activity level, and decreased vitamin D levels) are associated with lower BMD at the hip or lumbar spine in women with lupus; 2b) lupus risk factors (greater disease activity, greater disease severity, higher corticosteroid burden, use of anticonvulsant drugs, and the presence of renal disease) are associated with lower BMD at the hip or lumbar spine in women with lupus, after controlling for traditional risk factors forlow BMD; 3a) Women with lupus have accelerated bone loss at the hip and spine during two additional years of lupus disease compared with matched controls followed for two years; 3b) the effect of lupus on the rate of bone loss at the hip and spine is greater in Caucasian than in African-American women; 4a) Traditional osteoporosis risk factors (mentioned in 2a above) are associated with accelerated bone loss in women with lupus; and 4b) lupus risk factors (mentioned in 2b above) are associated with accelerated bone loss at the hip or lumbar spine in women with lupus, after controlling for traditional risk factors for low BMD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN AND GENDER BIASED AUTOIMMUNITY Principal Investigator & Institution: Rider, Virginia C. Associate Professor; Biology; Pittsburg State University Pittsburg, KS 66762 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2004 Summary: (Scanned from the applicant's abstract) Systemic lupus erythematosus (SLE) is an autoimmune disease that occurs primarily in women during their childbearing years. The effects of SLE are physically and emotionally debilitating and can be life threatening due to the involvement of a variety of organs including the renal and central nervous systems. Estrogen is a female sex hormone that acts on target cells though specific receptor proteins. Estrogen receptors (ER) are ligand activated transcription factors that bind to unique DNA sequences of target genes and alter the rates of transcription. In lupus T cells, estrogen increases the expression of calcineurin, a protein phosphatase involved in T cell activation. The proposed research will investigate the
Studies 45
molecular mechanisms by which estrogen, acting through the ER, significantly increases calcineurin, activates nuclear factor of activated T cells (NFAT), and augments CD4O ligand (CD4OL) expression in the T cells from female lupus patients but not in T cells from healthy individuals. The molecular mechanisms responsible for increased calcineurin expression in lupus T cells will be investigated using assays that distinguish transcriptional and posttranscriptional gene regulation. To determine if the differential control of calcineurin in lupus T cells is due to differences in the ratio of ER subtypes (ERa versus ERB), reverse transcription and quantitative polymerase chain amplification will be used to determine the amount of ER subtype transcripts. Altered ER binding to DNA regulatory elements will be assessed by electrophoretic mobility shift assays (EMSA). To investigate if the estrogen-dependent increase in calcineurin hyperactivates the transcription factor NFAT, the duration of NFAT dephosphorylation will be analyzed and the ratio of phosphorylated and dephosphorylated NFAT will be compared between T cells treated without and with estradiol. Biological activity over the same time points will be measured by comparing the amount of NEAT binding to consensus DNA sequences of the CD4OL promoter and by measuring changes in CD4OL expression in response to estradiol. The knowledge gained by completion of this study will identify potential sites in human lupus T cells at which to block signal transduction and decrease the abnormal synthesis of cytokines that promote inflammation and B cell activation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EUBACTERIA ERYTHEMATOSUS
IN
PATHOGENESIS
OF
SYSTEMIC
LUPUS
Principal Investigator & Institution: Kovacs, Shirley A.; California State University Fresno Fresno, Ca 93740-9999 Fresno, CA 93740 Timing: Fiscal Year 2001 Summary: Systemic Lupus Erythematosus (SLE) is an autoimmune arthritic disease of unknown etiology but behaves as an antigen-driven response to the nuclear component, U1 small nuclear ribonucleoprotein particle (U1snRNP). U1nsRNPs are highly conserved among eukaryotes but not thought to exist in prokaryotic organisms. However our work suggests that ribonucleoprotein particles displaying high homology to U1snRNPs do exist among eubacteria. As bacterial snRNPs could provide an antigenic stimulus which might lead to autoimmunity, a small group of SLE-susceptible MRL-lpr/lpr mice were injected with extracts from one of the "U1snRNP"-positive bacteria. The mice injected with bacterial extracts displayed early expression of certain clinical and immunological symptoms of SLE, commencing about two weeks after inoculation (mice were one month old at inoculation). This proposal intends to examine the details of this immune response through variations in immunization dose and time relevant to "natural" disease course and to include more thorough clinical, histopathological and immunological assessments of the outcomes. Clinical criteria will principally include assessments of arthritis, lymph node hyperplasia and alopecia; histopathological criteria will principally monitor tissue abnormalities in joints, kidneys and lymph nodes; and immunologic criteria will use ELISA reactivity to human nuclear extract and to bacterial extract for titers and isotypic profiles, direct immunofluorescence to detect glomerulonephritis, indirect immunofluorescence to detect reactivity to specific nuclear antigens, and western blotting to determine reactivity to U1snRNP-specific proteins MRL-lpr/lpr mice immunized with physiological saline and random genetic mice (Swiss-Webster) injected either the bacterial extract or saline will serve as experimental controls. Other candidate "U1snRNP"- containing bacterial organisms will
46 Lupus
be identified and/or evaluated using computer-based genomics, the polymerase chain reaction (PCR), northern hybridization and RNase protection assays, and mRNA splicing- complementation assays. Finally, the ability of these candidate prokaryotic cell extracts to stimulate SLE will be assessed by immunization of MRL-lpr/lpr mice and assessment of clinical, histopathological and immunological symptoms. The outcome of these experiments should provide a cleared indication of whether: inoculation with prokaryotic cells; and these latter pro-karyotic cells can also stimulate SLE symptoms in MRL-lpr/lpr model mice. The possibility that bacteria are etiological agents of SLE unveils a wealth of antibiotic therapeutic opportunities for treatment of SLE or other autoimmune, rheumatological disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXPERIMENTAL INDUCTION OF SLE BY ALTERED IA Principal Investigator & Institution: Eisenberg, Robert A. Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-JUL-1984; Project End 30-JUN-2003 Summary: (Adapted from the applicant's abstract) - The chronic GVH reaction is induced in inbred strains of mice by a transfer of spleen and lymph node T cells that recognize a foreign MHC class II determinant in the recipient. This syndrome is characterized by a spectrum of autoantibodies and immunopathological changes that closely parallels those found in human systemic lupus erythematosus. Previous work by the principal investigator's laboratory and others have shown that this disease is induced by the donor alloreactive T cells that recognize foreign MHC class II on B cells of the recipient that are in turn, induced to produce autoantibodies. In the current application, the principal investigator proposes to study the specific role of the donor and recipient T cells as well as the recipient B cells in chronic GVH. His specific aims are (1) To learn how B cell tolerance is lost in the chronic GVH reaction; (2) to understand what the role is of endogenous T cells in the chronic GVH response; and, (3) to determine what the role is of donor T cells in the chronic GVH response. These studies, the applicants expect, will provide important insight into the mechanism of autoantibody production and loss of tolerance in the chronic GVH response. This, they believe, will help in understanding the underlying mechanisms that produce the loss of tolerance characteristic of spontaneous systemic lupus erythematosus (SLE), both in mice and in humans. Such understanding will, eventually, lead to more rational therapy for this disease and other autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FC RECEPTOR FUNCTION IN NORMALS AND SLE Principal Investigator & Institution: Salmon, Jane E. Professor; Hospital for Special Surgery 535 E 70Th St New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-DEC-1992; Project End 31-AUG-2003 Summary: (Adapted from Investigator's abstract): Human Fc receptors (FcgR) consist of three families with extensive diversity of structure and function. Recent advances bring into focus four observations pertinent to SLE: 1) FcgRIIa is a crucial receptor mediating phagocytic function; 2) FcgRIIa is unique among FcgR in that it is targeted for oxidant and protease-induced amplification of effector function as well as avidity modulation, independent of receptor number; 3) the H131 allele of FcgRIIa is the only human FcgR which recognizes IgG2 efficiently; 4) the distribution of FcgRIIa alleles is skewed in SLE patients compared to normals, with a highly significant decrease in FcgRIIa-H131 in
Studies 47
lupus nephritis. In SLE, FcgR-specific immune complex removal by the mononuclear phagocytes system is impaired. This defect is related to renal disease, emphasizing the possible role of FcgR dysfunction in immune complex deposition and the pathogenesis of SLE. Despite the decrease in FcgR function in vivo , there is a paradoxical increase in FcgR binding in vitro. Preliminary data indicate that FcgRIIa is a compelling candidate for the FcgR dysfunction in SLE. Monocytes in SLE patients have increased FcgRIIamediated binding, but markedly decreased FcgRIIa phagocytosis, indicating dissociation of receptor-effector coupling. Disease-induced dysfunction superimposed upon inherited polymorphisms of FcgRIIa with decreased functional capacity may provide the milieu for the development of immune complex deposition and nephritis. Recent evidence for a role of IgG2 autoantibodies in nephritis underscores the importance of FcgRIIa in disease phenotype. Based on these observations, the investigators hypothesize that 1) abnormal FcgRIIa function provides a basis for diseaserelated defects in SLE, and 2) that alleles of FcgRIIa which affect ligand binding are important heritable disease susceptibility factors. Therefore, the specific aims of this application: 1. to define the mechanism of activation of FcgRIIa; 2. to define the basis for the defect in phagocytosis by FcgRIIa in SLE; 3. to define the role of FcgRIIa alleles as risk factors for lupus nephritis: (a) to establish genetic linkage of lupus and nephritis to FcgRIIa and (b) to define the relative importance of FcgRIIa alleles among different ethnic groups; and 4. to define subclasses of IgG deposited within glomeruli in lupus nephritis and their relationships to FcgRIIa alleles, autoantibodies, and induction of glomerular injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FREQUENCY OF MIF GENE POLYMORPHISM AND CUTANEOUS EXPRESSION Principal Investigator & Institution: Kang, Insoo; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: This is a new application for a YSDRCC pilot/feasibility grant from a clinically trained rheumatologist without NIH fundings who now seeks a financial support to initiate his research in determining Mif gene polymorphisms and cutaneous expression of MIF in patients with systemic lupus erythematosus (SLE). The mucocutaneous system is affected in 85% of patients with SLE. An important concept in the pathogenesis of SLE is that there is an intrinsically heightened state of T lymphocyte responsiveness that contributes to sustained T cell activation and autoantibody production. These events lead to recruitment and activation of inflammatory cells, such as macrophages, and subsequent tissue destruction in inflammatory sites. Several studies showed the requirement of macrophages in the development of murine lupus nephritis, suggesting an important role of macrophages as a pro-inflammatory migration inhibitory factor (MIF) is a pro-inflammatory cytokine secreted from monocytes, macrophages and T cells and has a pivotal, upstream role in activation of macrophages and T cells. Recently, a study identified promoter polymorphisms of the Mif gene that comprises the tetranuclotide repeat sequence (CATT)5-8. In rheumatoid arthritis (RA), a systemic autoimmune disease like SLE, a study showed that patients with RA had a decreased frequency of a single 5-CATT allele (lowest Mif expression), which was even lower in RA patients with mild disease. This suggests a potential role of Mif in the pathogenesis of T cell- and marcrophage-mediated autoimmune inflammatory diseases such as SLE and RA. Of interest, in psoriasis, an increased level of MIF was found in the skin and serum, suggesting a role of MIF in inflammatory skin
48 Lupus
diseases. Furthermore, a study showed induction of MIF in the skin by UVB, which is a well-known environmental factor for SLE. Based on these observations, a hypothesize that patients with SLE have increased expression of MIF, as a result of genetic predisposition, that promotes macrophasge-mediated inflammation and possibly T cell activation will be tested. To investigate this hypothesis, the following will be done. First, define the frequency of low- and high-expression Mif alleles in patients with SLE and correlate them with plasma MIF levels and disease activity. Second, determine the expression of MIF in skin lesions from patients with SLE and discoid lupus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL EXPRESSION OF SLE3/5 ON NON-B CELL APC'S Principal Investigator & Institution: Sobel, Eric S. Associate Professor; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001 Summary: This proposal is part of a systematic effort to functionally dissect the complex genetic leading to systemic lupus erythematosis (SLE or lupus). Essentially, our approach has been to use genome wide scanning to identity susceptibility loci contributing to the development of SLE, to transfer these loci onto the non-autoimmune C57BL/6 (B6) background, to determine a reproducible phenotype conferred by the interval, and to determine the lineage(s) in which the susceptibility locus is expressed. We identified 3 genomic intervals from NZM2410 that contributed to the development of glomerulonephritis. One of these, B6.NZMc7 [containing Sle3/5 on chromosome 7] develop low titers of IgG anti-nuclear antibodies, elevated CD4:CD8 ratios and mild-tomoderate immune complex glomerulonephritis (GN). We have recently completed a set of bone marrow adoptive transfer studies with B6.NZMc7 congenic mice. The NZMc7 locus was functionally expressed on bone-marrow-derived cells but not on radioresistant host cells. Moreover, the elevated CD4:CD8 phenotype could be reconstituted in radiation chimeras. Using Ly5-marked congenic strains and B6 host mice, additional experiments surprisingly demonstrated that the elevated DD4:CD8 ratio was not an intrinsic property of the T cells, and that a trend toward an elevated ratio could also been seen within the single-positive thymocytes. Preliminary data also indicated that the low-penetrant autoantibodies were not due to expression of the NZMc7 locus in B cells. Taken together, these data suggests that the effect is mediated by a bone-marrow-derived, non-B-cell antigen presenting cell (APC) present both in the thymus and secondary lymphoid organs. We propose that these APCs are dendritic cells, and may be the recently described lymphoid organs. We propose that these APCs are dendritic cells, and may be the recently described lymphoid subset, which are thought to be regulatory in nature. To test these hypotheses, we propose three Specific Aims: 1) to test the prediction that B6.NMc7 non-B-cell APCs are responsible for the elevated CD4:CD8 ratio; 2) to test the prediction that B6:NZMc7 dendritic cells have an altered threshold for inducing negative selection; and 3) to test the prediction that there is a difference in the kinetics of proliferation and apoptosis induced by BB6.NZMc7 APCs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENDER SPECIFIC T CELL HOMING AND AUTOIMMUNITY Principal Investigator & Institution: Adams, Matthew D. Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-JUL-2001
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Summary: Women are more susceptible to autoimmune diseases, and the reason is unknown. Female sex hormones appear to play a role in this predisposition to autoimmunity, but extensive analysis of the effects of the female sex steroids on immune responses in vitro have failed to identify the mechanism(s). The Richardson lab has used a new model of drug-induced lupus to identify novel gender- specific immune mechanisms. In this model, D10 cells, a cloned Th2 line, are made autoreactive by treatment with DNA methylation inhibitors, then injected into syngeneic mice. The autoreactive cells cause a more severe autoimmune disease in females than in males, and disease severity is diminished by oophorectomy. Significantly more of the cells, treated or untreated, are retained in the female spleens, and this selective retention also decreases following oophorectomy. Finally, splenectomy prevents the development of autoimmunity. These results demonstrate that T cell splenic homing differs between males and females, and that the spleen is essential for the development of disease. These results suggest that the greater disease severity in females is due to more autoreactive cells accumulating in the female spleens. The reversal by oophorectomy implicates female sex hormones in these differences. We hypothesize that gender-specific differences in T cell homing, due to effects of female sex hormones on adhesion molecule expression, contribute to increased severity of autoimmune diseases in females by modifying lymphocyte trafficking patterns. Gender-specific trafficking differences could be important both in the induction of disease as well as later in the disease process. Our model system provides a unique opportunity to directly test the role of sex hormones in modulating endothelial cell adhesion molecule expression and lymphocyte homing, and to relate these findings to the development and severity of autoimmunity. The specific aims are to: 1) Characterize the effects of sex hormones on T cell homing in vivo, 2) Define the effects of sex hormones and other signals on T cell and endothelial cell adhesion molecule expression and function in vitro, and 3) Define the role of those adhesion molecules whose expression is modified by sex hormones in splenic homing and disease severity. These studies may identify novel and important mechanisms contributing to the increased incidence and severity of autoimmune disease in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE MAPPING IN WOMEN W/ SYSTEMIC LUPUS Principal Investigator & Institution: Messner, Ronald; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001 Summary: Systemic lupus erthematosus is an autoimmune disease of unknown etiology. There is convincing epidemiological evidence that SLE clusters in families, suggesting a genetic basis for the disease. Our hypothesis, based on a large body of evidence, is that SLE is an oligogenic disease, with the inheritance of a few genes other than MHC and TCR contributing to susceptibility. We propose to use gene mapping with highly informative, short tandem repeat polymorphism's (STRPs) in sibling pairs and multiplex families with SLE. In the course of the study we will establish a detailed database of clinical and family history data, determine Class II genotypes, and establish a repository of sera, DNA and immortalized cell lines for each subject. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENES AND CHEMICAL EXPOSURE ASSOCIATED WITH SLE RISK Principal Investigator & Institution: Fraser, Patricia A. Associate Professor; Cbr Institute for Biomedical Research 800 Huntington Ave Boston, MA 02115
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Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 29-SEP-2003 Summary: Systemic lupus erythematosus (SLE) is an autoimmune, disabling, disfiguring systemic rheumatic disease that preferentially afflicts women and AfricanAmericans. The excess risk of SLE in African-Americans is not entirely explained by the genetic markers of susceptibility that have been identified to date. Sex hormones are immunomodulatory. During the interval between menarche and menopause women are exposed to significantly higher estrogen levels when compared to men of similar age. This gender difference in estrogen exposure may explain the gender imbalance in SLE risk. Similarly, African-Americans have higher levels of sex hormones than Caucasians. Genetic determinants of the observed ethnic differences in sex hormone levels may contribute to the ethnic differences in predisposition to SLE. Several polymorphic cytochrome P-450 genes encode enzymes in critical pathways of estrogen and androgen synthesis and degradation. Inter-relationships among these genes may be important genetic determinants of hormone levels that may also influence the hormonal effects on lupus susceptibility. Gene-hormone interactions affect hormone homeostasis of function and these, we hypothesize, can be affected by environmental agents. Through a variety of mechanisms, organochlorines in the environment such as 2,2-bis(rho-chlorophenyl)1,1,1- trichlorethane (DDT), and its long-lasting metabolite DDE may affect sex hormone homeostasis. We hypothesize that interactions of genes that affect sex hormone homeostasis and function (androgen receptor (AR) and estrogen receptors (ERs) and cytochrome P450 genes) with endogenous and/or exogenous estrogens and also with organochlorine exposures explain the gender and ethnic differences observed in SLE. The specific aims of this proposal are to: 1. Determine AR, ERs and cytochrome P450 genotypes in SLE subjects and controls by PCR based methodologies in a large SLE case/control study; 2. Determine the relative importance of genetic markers in Aim number 1 with endogenous and exogenous estrogens and with exposure to organochlorines in predicting risk of SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ANALYSIS OF ANTIPHOSPHOLIPID ANTIBODY SYNDROMES Principal Investigator & Institution: Ortel, Thomas L. Associate Professor; Duke University Durham, NC 27706 Timing: Fiscal Year 2001 Summary: Purpose: The purpose of this study is to understand the molecular basis of inherited antiphospholipid antibody syndromes as well as define the molecular mechanisms underlying the diverse pattern of clinical phenotypes and laboratory findings that have been observed in patients with antiphospholipid antibodies. Methods: We have established a registry of all individuals identified with a positive lupus anticoagulant and/or anticardiolipin antibody at Duke during the last five years. To date, we have identified over 570 patients with antiphospholipid antibodies. These patients are then recruited to participate in the studies described below. In addition, we have also enrolled family members from 39 of these patients, obtaining genomic DNA, plasma, and serum for characterization. Results: [1] To investigate the genetics of primary antiphospholipid antibody syndromes, we have identified 7 multiplex families that met stringent clinical and laboratory criteria for the diagnosis of a familial antiphospholipid antibody syndrome (APS). In these families, 23 out of 94 family members (24.5%) met criteria by either serologic or coagulation defects, or a combination of clinical, serologic and coagulation defects. Segregation studies rejected environmental and autosomal recessive inheritance patterns, and suggested that a
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dominant or co-dominant model would best fit the observed data in these families. Linkage studies showed independent segregation of APS and markers for several candidate genes. [2] To investigate the molecular basis of the observed clinical heterogeneity in these patients, we are screening patients for additional primary hypercoagulable states and correlating the presence of a second disorder with the occurrence of a thrombotic event. To date, we have screened 99 patients for the presence of three commonly encountered thrombophilic polymorphisms by restriction enzyme analysis of PCR-amplified genomic DNA: factor VR506Q; the 3'-untranslated prothrombin gene (PTG) polymorphism; and the thermolabile variant of methylene tetrahydrofolate reductase (MTHFR). Fifty-eight patients had primary antiphospholipid antibody syndrome (PAPS), 25 had systemic lupus erythematosus (SLE), 6 had other connective tissue disorders (CTD), and 7 were asymptomatic. Seventy-seven patients sustained one or more TE: 53 had venous TE, and 36 had arterial TE (12 had both venous and arterial TE). Fifteen of 58 female patients (25.9%) sustained one or more miscarriages. Eighteen patients had one or more thrombophilic polymorphisms: 8 were heterozygous for factor VR506Q, 3 were heterozygous for the 3' PTG polymorphism, and 9 were homozygous for the MTHFR polymorphism (including 2 who were also heterozygous for factor VR506Q). Eleven of 18 had PAPS (19%), 6 had SLE (24%), and 1 had CTD (16.7%). Sixteen of the 18 patients had sustained a venous and/or arterial TE (p=0.347). Two individuals homozygous for the MTHFR polymorphism had not sustained a TE. The presence of factor VR506Q or the 3' PTG polymorphism were associated with a significantly increased risk for a venous TE (10 of 11 patients; p=0.0095). In contrast, only 5 patients with the MTHFR polymorphism sustained a venous TE, including the 2 who were also heterozygous for factor VR506Q. None of the thrombophilic genotypes, alone or combined, were associated with an increased risk for arterial TE or miscarriage. Significance: The significance of these studies is that we will understand the genetics of an inherited autoimmune disorder as well as the molecular basis of the phenotypic heterogeneity observed in these patients. This will enable us to better identify patients at risk for developing a thromboembolic complication due to the presence of these antibodies. By defining which patients are at risk, we will be able to develop better therapeutic agents to prevent recurrent complications in these patients and also develop new clinical laboratory assays in order to better monitor their therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ANALYSIS OF EPITOPE SPREADING Principal Investigator & Institution: James, Judith A. Associate Professor; Oklahoma Medical Research Foundation Oklahoma City, OK 73104 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2005 Summary: Systemic lupus erythematosus (SLE) is a serious autoimmune disease of which the etiology and mechanisms of pathogenesis are incompletely understood. It is clear that there is an important genetic component to lupus. High titers of autoantibodies, which may include anti-Sm and anti-RNP are characteristic of lupus. Recent work shows that the natural history of these autoimmune responses is to increase in complexity by involving additional structures of the autoantigen in the autoimmune response. This process is termed epitope spreading detected in this proposal as added antigenic spine specificity through time. A similar phenomenon in T cell epitopes is very important in other models of disease, such as experimental autoimmune encephalitis. The applicants suspect that this process is also very important in lupus pathogenesis. Recently a new model of lupus autoimmunity was discovered by this group induced by immunization with a short sequence from Sm B/B'. This new
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model of induced SLE presents opportunities to explore the genes involved in B cell epitope spreading as well as the autoimmunity of lupus. Work here with the AKXL recombinant inbred set of mouse strains has preliminarily established linkage on chromosome 4 at B cell marker 72. They propose to apply the impressive tools of mouse genetics to identify the genomic region and perhaps the specific genes associated with anti-Sm B cell epitope spreading. They will subsequently explore the syntenic regions and homologous genes in human lupus. The goals of this proposal are to analyze genetic contributions to epitope spreading and recombinant inbred strains of mice and to confirm the findings by classical genetic approaches. It will seek to confirm and narrow the region of chromosome 4 by classical back cross experiments. Simultaneously the investigators will evaluate the candidate gene Cd72 for its potential role in the observed linkage. If Cd72 does not explain linkage in this recombinant inbred set, then confirmation of this region, and a search for different candidate genes will then pursue. They will then seek linkage in other recombinant inbred strains of mice and work to identify the responsible genes. Finally, linked regions and identified genes will be tested for their potential contribution to human lupus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ANALYSIS OF T CELLS IN LUPUS Principal Investigator & Institution: Craft, Joseph E. Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 01-JUL-1996; Project End 30-JUN-2006 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) is characterized by IgG autoantibodies to certain intracellular components, including chromatin and ribonucleoproteins. Several inbred mouse strains also develop spontaneous lupus, with the same spectrum of autoantibodies. Certain of these specificities are pathogenic, including those against chromatin that induce immunecomplex glomerulonephritis. Autoantibodies in lupus arise as a consequence of autoantigen-specific alpha/beta CD4+ T cell help, including T cells specific for peptides of chromatin-associated proteins. Such autoreactive T cells bypass normal tolerance mechanisms in the periphery; however, the mechanism of activation of T cells responsive to self peptides in lupus is unknown, as are the tissue source(s) of such peptides and the events leading to autoreactive CD4+ T cell-B cell collaboration with resultant pathogenic autoantibody production. In this proposal, an in vivo approach will be used to dissect the mechanisms that lead to peripheral T cell tolerance abrogation and T cell help for autoantibody production in lupus. It is hypothesized that these events arise in two stages: first, that lupus T cells have intrinsic (genetic) defects that render them susceptible to activation after contact with the ubiquitous self peptide-class II MI-IC complexes that are sufficient for CD4+ T cell survival in normal animals; second, that such activation, initiating tolerance loss with polyclonal expansion of autoreactive T cells, leads to oligoclonal T-B cell collaboration in the setting of specific autoantigen presentation by autoreactive B cells. The hypothesis will be addressed in two aims. First, it will be determined if normally displayed (ubiquitous) MHC-self peptide complexes can activate autoreactive T cells from Fas-intact mice MRL/+Fas-lpr mice, in comparison to non-autoimmune control T cells. Second, it will be determined if T cells from MRL/+Fas-lpr mice can provide B cell help in the setting of autoantigen presentation by autoreactive B cells, an event that leads to antigen-specific expansion of cells from both lineages. These objectives fit well within the overall context of this IRPO proposal centered around developing a better understanding of T cell-B cell interactions during the development and maintenance of systemic autoimmunity.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC CONTROL OF AUTOIMMUNITY IN LUPUS PRONE MICE Principal Investigator & Institution: Mcduffie, Marcia J. Associate Professor; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2001 Summary: We have identified three chromosomal segments, apart from the MHC complex, which contain genes that independently regulate progression of the pancreatic autoimmunity and beta-cell loss in non-obese diabetic (NOD) mice. Two of these genes, found on chromosomes 4 and 11, co-localize with chromosomal segments associated with one or more aspects of lupus-like disease in the NZB/NZW F1 model. This observation led to our first hypothesis: that genes located on chromosomes 4 and 11, which control- diabetes-susceptibility in NOD mice, promote the development of lupuslike disease in mice. We propose to define the location of lupus-susceptibility genes on chromosomes 4 and 11 in a recombinant-inbred mouse model of SLE, NZM2328. This will be accomplished by inhibiting disease expression with defined intervals of chromosome 4 and 11 taken from the non-autoimmune C57L/J strain and correspond to the locations of the chromosome 4 and 11 genes in autoimmune diabetes (Specific Aim 1). Using targeted breeding, we will then determine directly whether homologous NOD interval can reestablish disease expression after replacing C57L/J segments in this model (Specific Aim 2). Taken together, the results of the proposed experiments in Aims 1 and 2 will test the hypothesis that the lupus- susceptibility genes identified on chromosomes 4 and 1 represent "autoimmunity genes" common to at least two distinct models of spontaneous autoimmunity in mice. In addition to protection from insulitis, we show that introduction of C57L/J derived alleles into a defined segment of chromosome 11 supports normalization of defective immune responses and protection from invasive insulitis in NOD mice. These observations suggest the second hypothesis: that this region of chromosome 11 plays a fundamental role in the regulation of specific immune reactivity, with particular relevance to autoimmunity. In order to test this hypothesis, we will determine the mechanism of action of the chromosome 11 gene(s) in an induced model of autoimmunity resulting from immunization with Ro60 antigen (Specific Aim 3). These studies will allow us to define the genetic relationship between pathogenic immune responses and the regulation of inflammatory responses by genes on chromosome 11. The results of these experiment will provide insight in disease pathogenesis in lupus-like autoimmunity in mice, particularly in dependence regulation of immune responses and inflammation. In addition, they will determine whether common "autoimmunity genes" control the development of disease in two autoimmune disease with different manifestations. We postulate that genes of this type are very likely to have homologues in human autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC EXPRESSION IN SYSTEMIC LUPUS ERYTHEMATOSUS Principal Investigator & Institution: Aune, Thomas M. President; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2001; Project Start 01-MAY-1994; Project End 30-APR-2004 Summary: Systemic lupus erythematosus is a multisystem autoimmune disorder of unknown etiology and poorly understood pathogenesis. The heterogeneity of lupus makes it especially difficult to characterize and quantitate in either routine clinical care or in the setting of controlled clinical trials. These problems limit clinical studies of new
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therapeutic approaches. We propose to apply methods to analyze gene expression using microarrays to characterize patients with lupus with the following specific aims: 1. To compare 7 lupus patients and 3 control subjects for differences in gene expression on gene filter microarrays analyzing 20,000-30,000 gene sequences. 2. To further evaluate groups of related genes suggested by Aim #1 to be of importance in lupus using either selected microarays or RNA (Northern) blot analyses. 3. To examine the gene expression findings for correlations with clinical features, activity and severity of lupus. Studies of gene expression in subjects with lupus offer several advantages over existing approaches. In addition to providing a noninvasive, easily repeatable measure of immune system activation, the results can be quantified and compared for many subjects. More importantly, there is the real possibility of identifying new pathways of immune activation at the molecular level which may in turn suggest approaches to the development of novel therapeutic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC FINE MAPPING IN SLE PAIR FAMILIES Principal Investigator & Institution: Behrens, Timothy W.; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001 Summary: The familial clustering of systemic lupus erythematosus (SLE) and the high rate of concordance in monozygotic twins suggests a strong genetic component for susceptibility to SLE. As one approach to the identification of lupus genes, our laboratory is currently performing a genome-wide marker screen in an effort to localized the chromosomal regions that harbor lupus genes. Over 180 families with at least two affected SLE relatives (mostly sib pair families) are enrolled in this study. In preliminary studies, three distinct regions of human Chromosome 1 show evidence of possible linkage in an initial cohort of 105 SLE sib pair families. As the genome screen proceeds it is likely that other candidate intervals will emerge on other chromosomes. The primary goal of the SCOR project is to accelerate the gene search in the MN SLE family collection. This will be accomplished by sharing ongoing genotyping data with our colleagues at OMRF (project #2) to compare results in the two SLE family collections. Preliminary mapping results at MN will also be shared with our colleagues at UAB (project #3) to assist in their screening of Chromosome 1q candidate genes. The MN family collection will then be genotyped with markers from the OMRF study, so that linkage results can be directly compared. Interesting chromosomal regions ill then be prioritized for high density marker screens and fine mapping. Trio families (one SLE patient with both parents) collected as a component of this SCOR application will be used in disequilibrium mapping in the targeted areas. A variety of strategies will then be employed to identify the SLE gene(s) in these regions. The ultimate isolation and cloning of SLE genes will provide the first opportunity to understand at the genetic level the defects that lead to the clinical immune dysregulation characteristic of patients with lupus. These insights should suggest new avenues of treatments for this patients, including the potential for somatic gene therapy. Interestingly, lupus- prone families also have an increased incidence of other autoimmune diseases including rheumatoid arthritis, thyroid disease, and diabetes. Thus, the identification of genes that cause human SLE is likely to improve our understanding of the genetics and pathophysiology of organ- specific autoimmunity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC LINKAGE IN LUPUS Principal Investigator & Institution: Harley, John B. Professor; Oklahoma Medical Research Foundation Oklahoma City, OK 73104 Timing: Fiscal Year 2001; Project Start 01-JUL-1987; Project End 31-JAN-2005 Summary: The genetic basis of systemic lupus erythematosis has been pursued using the last five years of funding from this grant (AR24717-07 to -11) to help perform and evaluate a genome scan in lupus. These results considered with those of our closest competitor show 26 possible genetic linkages with 11 of these having some support for linkage from both studies. In addition, we confirm evidence supporting the presence of linkage at D1s229. Other work has advanced Epstein-Barr virus as a possible etiologic agent in lupus. Data show association, are consistent with Epstein-Barr virus infection preceding lupus onset, and advance a plausible mechanism for lupus autoimmunity in some patients. Virus exposure data and differences between the anti-viral immune responses of lupus patients and normal are amenable to genetic analysis in our pedigrees. In aggregate, we have 2109 pedigrees multiplex for lupus containing 1227 subjects (275 affecteds & 752 unaffecteds). We hope to continue our work by pursuing the following specific aims: 1. Enlarge the pedigree collection; 2. Establish linkage using: A. Lupus (by revised ACR criteria), B. An environmental factor and intermediate phenotypes: i. Lupus and Epstein-Barr virus infection, ii. Anti-peptide antibodies against Epstein-Barr virus (& against lupus autoantigens), iii. Anti-Ro and anti-nRNP autoantibody responses, and C. Multi-locus effects, and 3. Reduce linkage intervals and evaluate candidate genes. Hopefully, results from this resubmitted project will help elucidate the complex genetics of lupus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC MOUSE MODELS FOR CHRONIC INFLAMMATORY DISEASE Principal Investigator & Institution: Bullard, Daniel C. Assistant Professor; Genetics; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Systemic lupus erythematosus, Wegener's granulomatosis, and polyarteritis nodosa are chronic inflammatory diseases that have vasculitis as a major component. The pathogenesis of vasculitis in these and other disorders involves a complex interaction among inflammatory, genetic, and environmental factors. Evidence from both patient studies and in vitro models supports a central role for leukocyte/endothelial cell adhesion molecules, such as ICAM-1 and its beta2 integrin counterreceptors, in the development of vasculitis. However, the specific mechanisms by which ICAM-1 mediates vasculititic lesion formation are not clear. This project will use a straightforward genetic approach using the MRL/MpJ-Faslpr mouse model to define the ICAM-1-dependent pathways responsible for mediating vasculitis. MRL/MpJ-Faslpr mice containing mutations in ICAM-1, LFA-l, Mac-1 and P150/95 have now been generated and will be used to investigate the roles of leukocyte/endothelial interactions in lesion formation in vivo. The specific aims are to: (i) define, by comprehensive qualitative and quantitative analysis, the effects of ICAM-1 deficiency on development and progression, organ distribution, and inflammatory characteristics of lesions of vasculitis in MRL/MpJ-Faslpr mice; (ii) define the relative contributions of ICAM-1 in mediating neutrophil, lymphocyte, and monocyte adhesion to MRL/MpJ-Faslpr endothelial cells; (iii) determine the roles of ICAM-1 in neutrophilmediated damage to MRL/MpJ-Faslpr endothelial cells; and (iv) determine whether
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MRL/MpJ-Faslpr mice with null mutations in the ICAM-1 ligands CD11a (LFA-1), CD11b (Mac-1), or CD11c (p150/95) will alter development and progression, organ distribution, or inflammatory characteristics of lesions of vasculitis. Upon successful completion of these aims, detailed mechanistic information regarding the roles of ICAM-1 in mediating leukocyte/endothelial adhesion and damage during the development of vasculitis will be obtained. In addition, new insights will be gained towards the general understanding of the pathogenesis of vasculitis as well as other leukocyte-mediated vascular injuries such as transplantation arteriosclerosis, and other reperfusion injuries. There have been many requests for these mutant mice or materials derived from these models; therefore, these models are contributing significantly to ongoing research that is relevant to several NIH institutes, including NIAMS, NHLBI, and NIAID. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC PATHWAYS CONTRIBUTING TO SLE PATHOGENESIS Principal Investigator & Institution: Wakeland, Edward K. Professor; Microbiology; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2003; Project Start 30-SEP-1998; Project End 29-FEB-2008 Summary: (provided by applicant): This research program is focused on characterizing the genetic interactions that mediate fatal disease in the lupus-prone NZM2410 mouse model of SLE. During the previous grant period, we identified four suppressive modifiers and two epistatic susceptibility loci that impacted disease development in our B6-congenic model of lupus autoimmunity. We subsequently produced a collection of B6-congenic strains carrying these disease-enhancing or disease-suppressing genes and initiated a detailed characterization of their component phenotypes and epistatic interactions. These experiments have led to the development of a model proposing that severe disease is mediated by epistatic interactions among genes in three separate pathways, each impacting a distinct element of disease pathogenesis {Wakeland, Liu, et al. 2001 2262/id}. In this application, we are proposing to identify three of the genes that were detected in our genetic dissection of this epistatic disease model. The identification of these genes will provide insights into genetic mechanisms that can suppress the breach in tolerance mediated by Sle1, and will identify genes that exacerbate the severity of glomerulonephritis as a consequence of immune complex deposition. We have three specific aims: 1). To fine map and identify kidney-targeting genes in the Sle1 gene cluster. We have developed a nephrotoxic antisera assay that allows the rapid detection of genes that exacerbate the development of glomerulonephritis (GN) as a consequence of immune complex deposition in the kidney. We propose to utilize this assay to complete the fine mapping and identification of these two genes via positional cloning strategies. 2). To fine map and identify Sles1. Sles1 was the strongest suppressive locus detected in our linkage analysis of disease modifiers in the NZW genome. This gene specifically suppresses the breach in immune tolerance mediated by the Sle1 gene cluster. We have produced a series of congenic recombinants with truncated intervals that will allow the localization of Sles1 into a ~950 Kb genomic interval. We will complete this fine mapping analysis and identify Sles1 3). Characterize the component phenotypes and genetic interactions of Sles2, Sles3, Sles4, and Sle6. We propose to create a series of bi- and tri-congenic strains to assess their impact on disease pathogenesis. The long-term goal of these studies is to characterize the genetic interactions that enhance and suppress lupus pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC RISK FACTORS FOR PNEUMONIA IN SLE PATIENTS Principal Investigator & Institution: Freemer, Michelle M. Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2003; Project Start 15-JUL-2003 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) can be a severely disabling disease and may affect any portion of the respiratory tract. The most frequent lung disease in SLE patients is pneumonia. It constitutes a major source of morbidity as well as mortality in these patients. While many of the clinical factors predisposing SLE patients to infections have been investigated, the genetic risk factors for pneumonia have not been thoroughly examined. The University of California, San Francisco (UCSF) Lupus Genetics Project, represents a well-characterized, ethnically diverse cohort of patients. Furthermore, the availability of genotype analysis for these patients provides an ideal opportunity to determine the impact of genetic polymorphisms on SLE patients' risk of developing pneumonia. Interestingly, prior investigators have identified genetic risk factors for infections in healthy populations that correspond to some of the polymorphisms associated with the development of SLE Evaluation of the relationship between pneumonia and these polymorphisms in an SLE population will yield insight into whether the genetic risk factors identified in healthy hosts also account for the high infection rate observed in SLE patients. This information has significant clinical implications regarding SLE patients' need for immunization and antibiotic prophylaxis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC RISK FACTORS FOR SUSCEPTIBILITY TO INFECTION IN SLE Principal Investigator & Institution: Fessler, Barri J.; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001 Summary: Although mortality in patients with systemic lupus erythematosus (SLE) has decreased over the past three decades, infectious complications remain a significant cause of morbidity and mortality, accounting for approximately 20- 50% of all deaths. The profound influence of genetic background on susceptibility to infections has been well established. Recently, specific variants in the tumor necrosis factor alpha (TNFalpha) promoter and the genes encoding Fcgamma receptors and mannose binding lectin have been associated with an increased susceptibility to infections in certain populations. Polymorphisms affecting these same genes have also been associated with an increased risk of developing SLE or expression of specific lupus manifestations. However, the link between these genetic polymorphisms and risk of infections in SLE patients has never been examined. The aims of this study are: a) to determine the incidence of specific polymorphisms in the TNFalpha promoter and the genes encoding Fcgamma receptors and mannose binding lectin in SLE patients b) characterize the frequency, type and severity of infectious complications in a group of SLE patients as compared with controls c) determine whether the presence of one or more polymorphisms in the genes of interest is associated with an increased risk of infectious complications in SLE. One hundred and five SLE patients and controls matched for age, sex and ethnicity will be assessed over an 18-month period to determine the incidence and severity of infectious complications. The incidence of genetic polymorphisms affecting these candidate genes and the frequency of infections will be compared between the two groups to determine the level of risk. The identification of genetic
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markers that would distinguish SLE patients at increased risk for infection would make a profound impact on the outcome of this disease by allowing clinicians to institute appropriate prophylactic therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC RISK PROFILE IN LONGITUDINAL SLE COHORTS Principal Investigator & Institution: Petri, Michelle; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: There is a genetic predisposition to the disease systemic lupus erythematosus. Recent research has concentrated on several genes on chromosome 1. Several lupus centers are cooperating in the further study of these genes, especially whether they predict which organs lupus affects in individual patients. SLE patients and their parents are being invited to participate in this study. Patients and parents agreeing to participate will have blood drawn at the time they enter the study (approximately 50 cc or a little more than 3 tablespoons), which will be sent to the University of Alabama-Birmingham for genetic studies. Patients alone will have blood drawn (approximately 30 cc or 2 tablespoons) to determine autoantibodies. Socioeconomic and demographic data (i.e., age; gender; race; occupation; income; marital status; housing; health habits; and health insurance) will be obtained, because past studies have shown these factors are important in the outcome of lupus. Information on the past course of SLE will be obtained from medical records, and disease activity will be assessed (by Dr. Petri) during regular appointments, on a yearly basis. There will be updates by telephone (about every 6 months). Genetic material will be stored to help in the future search of genes that contribute to lupus. Confidentiality will be respected by coding the genetic samples. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC RISK PROFILE IN LONGITUDINAL SLE COHORTS Principal Investigator & Institution: Alarcon, Graciela S. Professor; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001 Summary: Both genetic and non-genetic factors contribute to the clinical presentations, clinical course, and outcome in SLE. To develop the theme of this SCOR, the genetics of SLE, and to translate the findings to the bedside by characterizing the clinical manifestations associated with the identified genetic markers, we propose to gather a population of well characterized SLE patients by joining efforts with investigators who already have ESTABLISHED longitudinal cohorts and the mechanisms to enroll NEW patients (Drs. Petri, John Hopkins University, MD; Reveille, University of Texas Health Sciences Center, Houston, TX; Ramsey-Goldman, Northwestern University, Chicago, IL) which will constitute the largest single available cohort of SLE patients for such studies (The PROFILE cohort)> With this cohort we will determine the extent to which a given genotype (PROFILE) determines the clinical phenotype. We will also contribute to the constitution of TRIO families for TDT analysis in order to confirm and narrow regions of genetic interest. The specific aims of the study are to: 1) Establish a multi-center common core database of SLE patients from multiple ethnicities comprised of patients who are already in local cohorts (ESTABLISHED) as well as NEW patients to be recruited; 2) Assess the ability of chromosome 1 genes (q21-32, see projects #1-3) to predict disease phenotype [renal, cardiovascular, pulmonary, and central nervous
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system, (CNS) involvement] in this PROFILE COHORT of SLE patients; 3) Establish a core set of TRIO families and work in conjunction with projects #1-3 and the Genetic Epidemiology and Biostatistics Core to use transmission disequilibrium to confirm the identification of candidate regions and genes in SLE. We have based our power and sample size calculations on the frequency of FcgammaRII H131/H131 in SLE patients with and without renal disease (8% versus 20%) and the frequency of renal disease among lupus patients from one of the center's cohorts. With total number of SLE patients of 600-700, we will have adequate power to demonstrate the skewing of this and other genes in the phenotype of the disease. Descriptive and analytical methods will be used where the phenotype will be the dependent variable and genetic (and other factors) the independent variables. The ability to predict the expression of the disease may have important implications for optimizing therapeutic strategies or developing new therapies for lupus patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS OF AUTOIMMUNITY Principal Investigator & Institution: Kotzin, Brian L. Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 01-APR-1986; Project End 31-MAR-2004 Summary: (Adapted from Investigator's abstract): The major goal of the studies proposed in this competitive renewal is to define further the genetic contributions to autoimmune disease in New Zealand hybrid mice that is a model of systemic lupus erythematosus (SLE). In previous studies, the investigator showed that the major dominant NZW contribution to disease was linked to H2, the murine major histocompatibility complex. Additional studies have mapped NZB susceptibility loci to chromosomes 1, 4, 7, 13, and 17 at H2. Congenic mice carrying these loci have been generated in the investigator's laboratory with the hypothesis being that each locus underlies an intermediate phenotype that in isolation reflects a single immunopathologic component of overall disease process. In Specific Aim 1 the investigator proposes to find out whether Ez and Az interact to control disease or if other H2 loci contribute to the MHC affect. Previously, the investigator identified a locus on chromosome 4 in NZB mice (Nba1) that he has introgressed onto NZW. This locus results in increased nephritis and mortality. In Specific Aim 2, the investigator proposes to identify the intermediate phenotype associated with this locus and to refine the support interval and number of candidate genes via congenic mapping. In Specific Aim 3, similar studies will be carried out using C57BL/6 and SM/J congenic mice carrying Nba2NZB, an NZB susceptibility locus on chromosome 1. The investigator purports to have identified a lupus-susceptibility locus that maps to chromosome 13 in C57BL/10 mice but is absent in C57BL/6 mice. Therefore, in Specific Aim 4 he proposes to take advantage of what he believes is a unique opportunity to identify this lupusenhancing gene. In Specific Aim 5 the investigator proposes to continue to derive and characterize SM/J mice congenic for NZB lupus-susceptibility loci on chromosomes 7 and 13. Taken together, the investigator suggests that the results of the studies proposed in this application will provide new insight into the genes that allow for autoimmune disease in SLE and the intermediate phenotypes that they control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETICS OF CHILDHOOD ONSET SLE Principal Investigator & Institution: Jacob, Chaim O. Associate Professor of Medicine and Immu; Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 30-JUN-2004 Summary: (Adapted from Investigator's Abstract) The etiology of systemic lupus erythematosus (SLE) includes poorly understood genetic, environmental and sexhormone factors acting on the immune system. The long term goal of this application is to identify genes involved in the etiopathogenesis of human SLE and to characterize the mechanisms by which these genes influence disease development. This application will also serve as a follow-up study of the initial linkage analyses performed in mouse models and in multiplex families. For this stage of mapping, the investigators propose to rely on association (linkage disequilibrium) studies in nuclear families as they will be able to collect a much larger study population than if they relied on the affected sib-pair pedigree approach. Childhood-onset SLE represents a potentially unique subgroup of patients because its early disease onset may be an indicator of increased genetic predisposition and penetrance, and because childhood-onset disease is more severe than adult-onset involving many organs and carrying a worse prognosis. The investigators therefore propose to study nuclear families of childhood-onset SLE subjects. Given that probands will be children, they anticipate that their parents and siblings will be available and strongly motivated to participate. The specific aims are as follow. 1) Recruitment and blood and DNA collection from 850 nuclear families containing at least one subject with childhood-onset SLE. They will classify all subjects for clinical and laboratory evidence of SLE, its organ involvement, severity of disease and complications. This will be accomplished using four recruitment study sites, which will provide large pediatric lupus populations. 2) Testing for association with specific candidate genes suggested by linkage, synteny and functional relevance using the family-controlled generalized transmission disequilibrium test (TDT) approach. 3) Exploring candidate regions of about 5 cM suggested by linkage and synteny for patterns of linkage disequilibrium by testing for marker associations and haplotype sharing. Initially, they will use markers spaced roughly 0.5 cM apart in each region, with promising leads followed up at a 0.05 cM marker spacing. The investigators point out that this application integrates the talent of a multidisciplinary team, combining clinical expertise with highly qualified basic scientists and with genetic, epidemiological, molecular biological and genetic analytic expertise. They further state that this is a multi-center application from some of the largest pediatric lupus clinics in the country and, therefore, represents a major and unique resource for the study of the genetics of childhood-onset SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETICS OF LUPUS-RELATED AUTOIMMUNITY IN HUMANS Principal Investigator & Institution: Moser, Kathy L. Assistant Professor; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-AUG-2003 Summary: The possibility that different autoimmune phenotypes might share particular genetic linkages has been bolstered by a meta-analysis of the available data (Becker, et al, PNAS 95:9979-9984, 1998). In addition, our collection of pedigrees multiplex for systemic lupus erythematosus (SLE), as a clinical disease, contain many members who do not have lupus, but who do have autoimmune findings. Examples include lupus-
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related positive serology and other disorders thought to be autoimmune in origin such as myasthenia gravis, rheumatoid arthritis, scleroderma, Sjogren's syndrome, psoriasis, and diabetes. Recently, we published the results of a genome scan using clinical lupus as a phenotype (Moser, et al. PNAS 95:14869-14874, 1998). In 94 pedigrees studied, there are 223 confirmed SLE affecteds and 594 family members, 17 percent of who report the presence of another autoimmune disorder and over 30 percent with positive autoimmune serology. In classic work, Bias and coworkers (Am J Hum Genet 39:584602, 1986) have shown that pedigrees ascertained on lupus and evaluated using humoral autoimmunity as an intermediate phenotype segregate this trait in an autosomal dominant pattern. We propose to use our now larger collection of pedigrees multiplex for SLE as a basis from which to seek evidence for the predicted autosomal dominant linkage as well as for other genetic effects. We will use our currently available collection of 173 pedigrees containing 1300 individuals to: 1) evaluate for a LupusRelated Autoimmune (LRA) phenotype, 2) seek linkage, and 3) perform fine mapping in regions providing evidence for linkage. Identification of genes that govern the propensity to develop autoimmunity has potential to provide important insight into mechanisms of etiology and pathogenesis that are common among multiple autoimmune diseases. Understanding these underlying pathological events will lead towards new opportunities for development of more effective mechanism-based therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GL701 ERYTHEMATOSUS
IN
FEMALES
WITH
ACTIVE
SYSTEMIC
LUPUS
Principal Investigator & Institution: Petri, Michele; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: Current medications for systemic lupus erythematosus do not completely control symptoms of the disease and/or can have side-effects. GL701 is a form of DHEA (dehydroepiandrosterone), an investigational drug, that has shown benefit in studies of lupus patients. This multi-center study will determine if DHEA (200 mg) works better than a placebo for SLE in 300 women who have active lupus, but are taking prednisone doses of 10 mg or less. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GUIDELINES FOR STEROIDS IN CHILDREN WITH LUPUS Principal Investigator & Institution: Brunner, Hermine I. Assistant Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, OH 45229 Timing: Fiscal Year 2003; Project Start 08-MAY-2003; Project End 30-APR-2006 Summary: (provided by applicant): BACKGROUND: This is a pilot study to evaluate the use of steroids and other medications in children diagnosed with SLE (cSLE). After having revolutionized the prognosis of lupus in the 1950s, steroids remain the mainstay of therapy of cSLE. Recent studies suggest that, despite their proven benefits, steroids contribute to the development of permanent disease damage in both adult and pediatric SLE patients. 10-year patient survival is only at 85%. Preliminary data support that there is a considerable degree of practice variation among pediatric rheumatologists treating cSLE and that these differences in treatment approach may have an impact on patient outcomes. There are no published guidelines of how to best treat cSLE, especially how to use steroids for its the treatment and when to introduce other steroid-sparing
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medications. GOALS: 1) To document treatment patterns of pediatric rheumatologists for patients with cSLE in order a) To identify key factor that prompt physicians to choose a certain steroid dose and document the factors that make physicians change a given dose of steroids; b) To identify the key variables that prompt physicians to introduce of immunosuppressive therapies for patients diagnosed with cSLE. 2) To measure quality of life and specific outcomes (damage, costs) associated with the treatment of children and adolescents diagnosed with cSLE. STUDY DESIGN: A cohort of consecutively sampled patients treated for cSLE (n=70) at 4 pediatric US and Canadian Rheumatology Centers (Chicago, Cincinnati, Minneapolis, Toronto) will be assessed in at least tri-monthly intervals over an 18-month period regarding their disease course (disease activity, number of flares, infection and hospitalization), treatments, and outcomes (damage, quality of life). Key determinants that prompt the physicians to use certain therapies will be recorded. Relevant retrospective patient information will be obtained by chart review. Patient quality of life and treatment costs will be measured. Correlation, regression, multivariable modeling including repeated measure analysis will be used to analyze the relationship of cSLE therapies to outcomes (damage, quality of life, costs) and to key determinants of treatment decisions in cSLE. SIGNIFICANCE: The proposed pilot study will provide information regarding physician treatment patterns, cost of cSLE and patient quality of life. Data will be collected to support that there are important differences in the approach to cSLE therapy that have a significant impact on patient outcomes. Results of the study will be used to generate hypotheses towards improved treatment approaches for cSLE. The proposed study constitutes a first step towards the development of evidence-based guidelines. Information on HRQL and costs of patients diagnosed with cSLE is required for future cost-effectiveness analyses of treatments for cSLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFICATION OF SLE1B AND IT'S ROLE IN AUTOIMMUNITY Principal Investigator & Institution: Wandstrat, Amy E. Center for Immunology; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: Systemic lupus erythematosus (SLE) is a complex genetic disorder and occurs 8-9 times more frequently in women than men with variable penetrance. In the lupus-prone mouse strain, NZM 2410, four regions have been identified on chromosomes 1, 4, 7, and 17. We are interested in identifying the gene(s) known to be responsible for the autoimmune response seen in SLE. Isolated in congenic mouse strains against a C57BL/6 background, the chromosome 1 region, Sle1, has been associated with either loss of tolerance to chromatin or increased immune response leading to splenomegaly and production of autoantibodies. The region of murine chromosome 1 that Sle1 maps to is syntenic to human chromosome 1 where a locus for lupus susceptibility has been linked (29- 33). Therefore, identification of the mouse gene may also help in identifying the human gene. We have been able to further narrow the Sle1 region using congenic meiotic recombinants and have found that there are three genes in the Sle1 region, Sle1a, Sle1b, and Sle1c that confer autoantibody production. Our studies have revealed that Sle1b is the strongest of the three loci regarding antichromatin IgG production. We have a sequence-ready BAC contig of the region and will use both BAC sequencing and cDNA direct selection to identify candidate genes for Sle1b. Candidate genes will then be analyzed for proper expression and the ability to reproduce the phenotype in a B6 mouse knockout. As Sle1b may be important in
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focusing the autoimmune response to selected targets, identification of the gene will be important in understanding how the autoimmune cascade is initiated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFICATION OF THE EARLY ONSET SLE GENE ON 17P13 Principal Investigator & Institution: Sestak, Andrea L.; Oklahoma Medical Research Foundation Oklahoma City, OK 73104 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): Ongoing studies at the OMRF have recruited and genotyped over 160 families multiplex for systemic lupus erythernatosus (SLE). Subgroup analysis of those families containing at least one SLE patient with age of onset less than 16 has revealed a putative susceptibility gene for early onset lupus with a lod score of 3.0 at 17p13. Independent analysis of affected relative pairs in the 160 family collection, using a principal component approach, confirms that age of onset is a major covariate, producing a lod of 4.4 at the same site, D17s1298. We have designated this putative susceptibility gene SLE pediatric 1 (SLEP1), and the goal of this application is to find and characterize this gene. First, we expect that an additional 30-45 families containing at least one member with pediatric onset SLE will become available from ongoing efforts to recruit multiplex pedigrees at OMRF, and we will seek to confirm the effect at D17s1298 in a second cohort. If successful, we will use fine mapping techniques, first with additional microsatellite markers and later with SNPs, to narrow the region of interest to 2-3 cM. Next, we will evaluate potential candidate genes in the narrowed susceptibility region by genotyping at SNP markers in known genes in the region and analyzing these by linkage disequilibrium methods. At this stage, priority will be given to any genes in the region with a plausible role in autoimmune pathogenesis. Finally, if the SNP selected to identify the gene through linkage disequilibrium to SLE does not prove to be the causative mutation, we will sequence the putative susceptibility gene and attempt to discover the functional mutations leading to SLEP1. This project is proposed in support of a K08 Mentored Clinical Scientist Development Award. It is relevant to the career goals of the principal investigator, both as a pediatric rheurnatologist and as a new scientific investigator. This project has the potential to increase our understanding of the genetic factors contributing to the pathogenesis of early onset SLE, as well as lupus in general. It will allow the principal investigator to interact with a number of collaborators and to become more familiar with the state of the art genotyping and biostatistical analysis techniques currently used in the OMRF lupus genetics project. In addition, this project has the potential to generate related projects in molecular biology that would allow the principal investigator to become fully independent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IDENTIFYING GENES FOR NEUROPSYCHIATRIC LUPUS Principal Investigator & Institution: Mishra, Nilamadhab; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, NC 27157 Timing: Fiscal Year 2002; Project Start 11-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) is a chronic, idiopathic autoimmune disease characterized by episodic flares and progression of disease, substantial morbidity and mortality(l, 2). It is a multisystern rheumatic disease with a wide variety of associated clinical neurological and psychiatric syndromes including cognitive, behavioral, affective, and/or motor manifestations that may effect
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up to 75 percent of SLE patients(3). Both morbidity and mortality remain high because of lack of understanding of the underlying mechanisms related to abnormal central nervous system (CNS) function. In addition, progress has been hampered by the lack of specific diagnostic methods and therapeutic regimens. A long-standing challenge has been to discover drugs that can halt the progression of disease by inhibiting the ongoing pathologic immune responses while maintaining physiologic immune surveillance. An ideal therapeutic approach would be to modify the expression of the genes that contribute to immunopathogenesis of neuropsychiatric lupus (NPLE). Although the genes responsible for neurological disturbances in SLE is not finely dissected out, preliminary studies in mouse models of lupus suggests aberrant cytokine genes expression in hippocampus and cerebellum are responsible for the neurological deficit(3-5). Our laboratory has recently demonstrated that the histone deacetylase (HDI) inhibitor Trichostatin A (TSA) reverses the skewed expression of several genes implicated in the immunopathogenesis of SLE(6). TSA significantly down-regulated CD154 (CD40-ligand) and IL-10 mRNA and protein, while simultaneously upregulating IFN-g message and protein levels in human SLE PBMC/T cells. Furthermore, our preliminary data in MRlJIpr mouse model of lupus demonstrates that this inhibitor down-regulates IL-10, IL-6, IL-12p30, IL-12p40 and IFN-g mRNA and protein secretion in MRL/Ipr splenocytes. Since IL-6, IL-10 and IFN-g genes are over expressed in cerebellum and hippocampus in MR/Ipr lupus, we propose the concept that HDIs may be useful for the prevention or treatment of neuropshychiatric lupus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IDENTIFYING THE VITILIGO RELATED SLE GENE ON 17P13 Principal Investigator & Institution: Nath, Swapan K.; Oklahoma Medical Research Foundation Oklahoma City, OK 73104 Timing: Fiscal Year 2002; Project Start 05-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Recently, we published tantalizing evidence locating a gene affecting susceptibility to systemic lupus erythematosus (SLE), and possibly vitiligo, in vitiligo related lupus families on 17p13 (1). Our goal for this proposal is to narrow the susceptibility region and to identify the susceptibility gene. We will achieve this by iterative reduction in the size of the chromosomal region. To improve the power of the study, specific aim 1 is to first augment our current data with new data, identified from our ongoing SLE genetic linkage projects. We will then narrow our previously identified susceptibility region in two steps. First, in specific aim 2, we will choose microsatellite markers to form a 1-2 cM map across the current susceptibility region and analyse these data using genetic linkage methods. Second, in specific aim 3, we will choose single nucleotide polymorphism (SNP) markers to form a 0.5 cM map across the reduced region from specific aim 2 and analyse these data using linkage disequilibrium methods. In the final step, specific aim 4, we will search the public databases for SNPs in genes known to be located in the narrowed susceptibility region established by specific aim 3 and to analyse these using linkage disequilibrium methods. Specific aim 5 is to sequence the gene to find the causal mutations. We ascertained families with European American ancestry, multiplex for SLE and each family has at least one member afflicted with vitiligo. Since autoimmune diseases are thought to share some of their genetic origins, decreasing sample heterogeneity would increase the power to identify the susceptibility gene(s). As the presence of vitiligo in the family was used as a pedigree ascertainment criterion, and there was significantly higher risk associated with developing vitiligo among the family members affected with SLE compared to non-SLE family members, we postulated the following hypotheses: SLE and vitiligo may share
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common autoimmune genetic determinant(s) for their pathophysiology. Alternatively, we may assert that there are genes that lead primarily to develop SLE, which may also modify the risk of developing vitiligo, at least among the ascertained families. Our preliminary results support the hypothesis that SLE and vitiligo may share common genetic determinant(s) (1). This project is directly relevant to the goals of NIAMS SMALL GRANT PROGRAM FOR NEW INVESTIGATORS and has the potential to reveal important, previously unappreciated, susceptibility genes, which contribute toward understanding the etiology of SLE and vitiligo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IG CLASS SWITCHING IN LUPUS B CELLS Principal Investigator & Institution: Casali, Paolo; Professor; Pathology and Laboratory Medicine; Weill Medical College of Cornell Univ New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-MAY-2000; Project End 30-APR-2005 Summary: The long term goal of this proposal is to gain insight into the mechanisms underlying the generation of autoantibodies in systemic lupus erythematosis (SLE), a major human autoimmune disease. The predominant and pathogenic anti-self response in these autoimmune patients consists of autoantibodies to nuclear components, including DNA. The origin of these autoantibodies remains enigmatic, but antibodies with similar binding activity are expressed by the normal B cell repertoire (natural autoantibodies). Compared to naturally occurring anti-DNA autoantibodies, lupus autoantibodies of similar specificity are "affinity mature", i.e., they are somatically mutated and antigen-selected. In addition, while the former are IgM, the latter are in general IgG, suggesting that class switching, a crucial mechanism in the maturation of any antibody response, is also important in the generation of autoantibodies in SLE. In class switching to IgG, the constant (C) region of the mu H chain is replaced by Cgamma region, resulting in the acquisition of novel biological activities, including the ability to pass into the extravascular space, and, therefore, in the case of autoantibodies to produce tissue damage. IgG-switched B cells are numerous in the circulation of SLE patients, and IgG accounts for the majority of the pathogenic autoantibodies in these patients. We formally argue here that class switching to IgG occurs more frequently and more effectively in lupus mu+ B cells than in normal mu" B cells. We further argue that this enhanced IgM->IgG switching results from a higher expression of CD40L by lupus T and B cells, as well as from a higher switching propensity of the B cells of these patients, due to a polymorphism of the Cgamma gene promoter or switch regions, and/or to dysregulation of the CD30-dependent mechanism that, as we have recently shown, physiologically dampens IgG-inducing stimuli. To test our hypothesis, we propose: (i) to study CD40L expression in SLE B cells, and their capacity to promote switching to IgG hypothesis, we propose: (i) to study CD40L expression in SLE B cells, and their capacity to promote switching to IgG using our unique in vitro human monoclonal (CL-01) IgM+ IgD+ B cell system; (ii) to analyze the in vitro spontaneous and CD40:CD40-induced IgG class switching in SLE IgM+ IgD+ B cells; (iii) to analyze the regulatory regions upstream of the Cgamma1, Cgamma2, Cgamma3, and Cgamma4 genes in SLE patients, their family members, and for comparison healthy subjects; and finally, (iv) to analyze the down-regulation of the CD40-mediated Ig class switching by CD30, another cell surface molecule of the TNFR family, and the interference with this mechanism by soluble CD30. The proposed experiments should further our understanding of the means that lead to Ig class switching and generation of IgG autoantibodies in lupus, and may help design specific means of therapeutic intervention.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNE ABLATION AND HEMATOPOIETIC STEM CELL SUPPORT IN PATIENTS WITH SLE Principal Investigator & Institution: Burt, Richard; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2001 Summary: Systemic lupus erythematosus pursues an aggressive course in a minority of patients, marked by Class III and Class IV nephritis, catastrophic anti-phospholipid syndrome, severe hematologic aberrations, or vasculitis, manifested by recurrent neurologic deficits, pulmonary parenchymal disease, or myocarditis. This subset of patients currently is treated with repeated courses of high dose glucocorticoids or cyclophosphamide. It is the nature of the persistent loss of self-tolerance that characterizes SLE that anti-self antibodies recur after a course of immunosuppression. Anecdotal evidence, derived from the responses of individuals with immunologic diseases who have received bone marrow transplantation for malignancy, suggests that the immune reconsistitution that occurs after transplantation can occur with acquisition of new tolerance to self-antigens. To allow the immune system to reconstitute itself from the stem cell progenitor after immune ablation, in the absence of any previously inciting antigenic stimulus, may allow extended remission from immunologic disease. The prior success of cyclophosphamide therapy, given in more moderate dosage, in curtailing organ-threatening and life-threatening manifestations of lupus, makes it a logical choice for immune ablation therapy. The use of anti-thymocite globulin in conjunction with cyclophosphamide therapy should prolong the inversion of CD4/CD8 cells, which normally characterizes immune reconstitution for a year after marrow ablation. It is hoped that a prolonged tolerance of self-antigens will be facilitated by this condition. By serologic as well as clinical parameters of disease activity, it should be possible to monitor the durability of this tolerance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMMUNE MECHANISMS IN PRISTANE INDUCED LUPUS NEPHRITIS Principal Investigator & Institution: Reeves, Westley H. Professor; Medicine; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: Intraperitoneal injection of pristane (2,6, 10, 14- tetramethylpentadecane) induces a lupus-like syndrome in nearly all "normal" strains of inbred mice. This syndrome is characterized by disease-specific autoantibody production (anti-Sm, RNP, Su, ribosomal P, double stranded DNA), hypergammaglobulinemia, and severe immune complex-mediated glomerulonephritis closely resembling lupus nephritis. In preliminary studies, it was shown that the disease develops in two phases, each with characteristic types of autoantibodies. cytokines, and renal involvement. Microbial stimulation was found to be an important co-factor in progression to the second. more severe, phase. This project will examine the hypothesis that immune complex deposition is necessary, but not sufficient, for the development of nephritis in pristane-induced lupus. Further, it is hypothesized that a systemic abnormality in macrophage or monocyte phenotype resulting from pristane and/or microbial stimulation leads to the production of proinflammatory cytokines and disease progression. The goal of this project is to define pathways leading to glomerulonephritis in pristane-treated mice and
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ultimately to relate them to human lupus nephritis. Three specific aims are proposed. The pathology of the renal lesions will be defined in Aim 1. Mesangial and mesangiocapillary lesions will be studied by immunohistochemical techniques to determine whether hypercellularity reflects proliferation of endogenous (mesangial or endothelial) cells vs. influx of exogenous macrophages, lymphocytes or neutrophils. In addition, mesangial matrix deposition will be evaluated, and the time course of the renal changes will be studied. The roles of pro-vs. anti- inflammatory cytokines will be evaluated in Aim 2. Cytokine production in the glomerulus will be compared with that by phagocytes in the peritoneal exudate, spleen and liver to see if systemic abnormalities are present. Expression of cytokine-inducible markers will be studied as a means to evaluate whether the effects of pro-or anti-inflammatory cytokines predominate. The contribution of microbial stimulation to the development of nephritis in pristane-induced lupus will be examined in Aim 3. It is hypothesized that enhanced intestinal permeability resulting from pristane injection increases the translocation of microbial products, such as lipopolysaccharide, into the bloodstream. This may cause systemic activation of monocytes and macrophages, which then are recruited to the glomerulus in response to immune complex deposition, causing progression instead of resolution of the renal lesion. In view of the widespread susceptibility among "normal" mice to pristane-induced lupus, it seems likely that pristane causes lupus- like disease by its effects on a common, distal, part of a lupus pathway, largely bypassing the genetic abnormalities that predispose to spontaneous forms of the disease. The mechanisms involved in this new inducible model of SLE may, therefore, be common to other forms of lupus, including human SLE. Future studies will address the question of whether renal abnormalities similar to those induced by pristane are involved in the pathogenesis of human lupus nephritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOLOGIC MECHANISM IN LUPUS NEPHRITIS Principal Investigator & Institution: Madaio, Michael P. Professor of Medicine; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001; Project Start 01-JAN-1985; Project End 30-JUN-2003 Summary: (Adapted from Investigator's Abstract): The overall aim of this project is to develop a better understanding of the immunologic events leading to glomerular immune deposit formation in individuals with Systemic Lupus Erythematosus. In previous studies, murine and human monoclonal anti-DNA antibodies (Ab) were identified that produced glomerulonephritis following transfer to normal mice. Of particular relevance, the location of immune deposit formation and disease phenotype varied with the mAb. Furthermore, these individual pathogenic Ab bound directly to glomerular cell surface antigens, however each monoclonal anti-DNA Ab recognized a different cell surface proteins. Based on these observations, it was postulated that different autoantibody-glomerular antigen interactions, in vivo, contributes to the phenotypic diversity observed both among the monoclonal Ab and among individuals with lupus. A primary goal of this project is to fully identify the glomerular cell surface antigens for three nephritogenic lupus autoantibodies: anti-DNA MES and anti-DNA SE, derived from MRL-lpr/lpr mice; and RH-14, a human anti-DNA Ab. Anti-DNA MES produces mesangial deposits and binds to mesangial cells, whereas anti-DNA SE produces subendothelial deposits and binds to glomerular endothelial cells. RH14 produces massive subendothelial deposits on transfer to SCID mice, and it binds to glomerular endothelial cells. Candidate cell surface protein antigens were isolated for the autoantibodies. Peptides derived from the isolated proteins will be sequenced and
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then used to generate both degenerate oligonucleotides and anti-peptide antibodies to screen cDNA libraries, in order to define the full sequence and identity of the immunoreactive proteins. Another primary goal of the project is to further determine the pathogenic relevance of these autoantibody-glomerular cell interactions by examining: i) the immune response to the purified cell surface proteins, ii) other spontaneously produced autoantibodies with anti-cell surface protein activity; and iii) the cellular and functional consequences of Ab ligation of the cell surface proteins. Studies will be performed to begin to determine the overall relevance of direct binding of human lupus autoantibodies to glomerular antigens, in general, using: human lupus sera from the Lupus Collaborative Study and controls, the purified cell surface antigens, and individual glomerular cells. Collectively, the results should identify diseaserelevant glomerular antigens for pathogenic lupus autoantibodies and provide insights into the overall pathogenic relevance of autoantibody-glomerular cell surface antigen interactions in lupus nephritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOREGULATORY ERYTHEMATOSUS
NK
T
CELL
/SYSTEMIC
LUPUS
Principal Investigator & Institution: Porcelli, Steven A. Associate Professor; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: A population of T lymphocytes known as NK T cells recognizes specific lipid ligands in the context of MHC class I-like CD1d molecules and has recently been found to contribute to the regulation of immune responses and the maintenance of immunological tolerance to self antigens. Numerous published reports have linked the loss of NK T cells and changes in their function to the progression of autoimmune diseases, including systemic lupus erythematosus (SLE) and mouse models of this disease. The central hypothesis of the current proposal is that NK T cells constitute an important regulatory arm of the immune system that normally assists in preventing the development of aggressive autoimmunity such as that which occurs in full-blown SLE. The proposed studies will evaluate changes in NK T cells during the progression of spontaneous lupus-like disease in NZB/W F1 mice, and will determine the influence of NK T cells on SLE-associated autoantibody production in murine models of spontaneous and induced SLE-like disease. These studies will build on preliminary findings that strongly implicate NK T cells as a major factor in the regulation of marginal zone B cells, a distinct B cell subset with inherent autoreactivity that has recently become a significant focus for research into the origins of autoantibody production in SLE. Methods that should allow the direct stimulation of NK cells in vivo will be investigated as potential approaches to therapy of SLE that could take advantage of the natural functions of these regulatory T cells. The program project format provides an optimal environment for these studies by providing numerous collaborative interactions with the other members of the program who bring it a wealth of expertise and resources for the analysis of murine models of SLE that are highly relevant to this proposal. These studies will also benefit from extensive usage of all of the Program's proposed core facilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPACT OF HRES-1 ENDOGENOUS RETROVIRUS IN SLE Principal Investigator & Institution: Perl, Andras; Professor; Medicine; Upstate Medical University Research Administration Syracuse, NY 13210
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Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by circulating antinuclear autoantibodies and dysfunction of T and B lymphocytes. Both genetic and environmental factors are believed to influence development of the disease. Common lupus autoantigens show potent immunological cross-reactivities with proteins of viruses and endogenous retroviral elements. Autoantibodies to HRES-1/p28, a 28 kD nuclear protein encoded by the HRES-1 human endogenous retrovirus, were found by several laboratories in up to half of the patients with SLE and overlap syndromes (OLS). We documented molecular mimicry between HRES-1, another nuclear autoantigen, the 70K component of U1 snRNP, and infectious viral core proteins. Analysis of molecular mimicries may provide clues to the identity of viral antigens responsible for triggering cross- reactive immune responses. We detected and cloned the HRES-1 human endogenous retrovirus and mapped it to chromosome 1 at q42. We identified polymorphic genotypes in the long terminal repeat (LTR)/promoter region of the HRES-1 genomic locus and revealed their association with SLE. HRES-1 is centrally located at 1q42 with respect to microsatellite markers associated with disease susceptibility. Thus, HRES-1 or a gene in linkage disequilibrium with this genomic locus may influence autoimmunity in SLE. Genetic variations of the HRES-1 LTR may be linked to a high degree of spontaneous and 5-azacytidine-inducible fragility of the 1q42 chromosomal region. 5-azacytidine, a demethylating agent, capable of triggering autoreactivity of T cells, may influence structure and activity of the HRES-1 LTR. The specific aims will test the hypotheses that (i) identification of HRES-1 autoepitopes with regions of homology to viral proteins and other autoantigens may pinpoint pathogens responsible for initiating autoreactivities, (ii) genetic composition of the HRES-1 LTR directly or indirectly influences development of SLE, and (iii) genotypes of the LTR region determine promoter activity and expression of HRES1/p28. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPACT OF LUPUS SUSCEPTIBILITY LOCI ON B CELL TOLERANCE Principal Investigator & Institution: Mohan, Chandra; Associate Professor; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 15-JAN-1998; Project End 31-DEC-2002 Summary: Problem: The function of the immune system is to distinguish self from nonself. When self-tolerance is lost, auto-immunity ensues. Systemic lupus erythematosus is a prototypic auto-immune disease, where loss of tolerance to nuclear antigens leads to a plethora of autoimmune pathology. Yet, little is known about which tolerance check points or mechanisms are actually breached in this disease. Parallel advances in the fields of B- cell tolerances, and genetics of autoimmunity, now allow us to investigate this in a systematic manner. Research Design: The use of immunoglobulin transgenics allows us to assess the integrity of B-cell tolerance at successive check points: deletion, receptor-edition, follicular exclusion, and anergy. Also, the availability of B6 congenic strains bearing individual lupus susceptibility intervals, allows us to evaluate the impact of each of these loci on B-cell tolerance, in a systematic way. This proposal will focus on two such potent loci, originally derived from the NZM2410 lupus strain: Sle1, which is responsible for triggering a strong anti-nuclear humoral response, and Sl32, which leads to spontaneous B-cell hyperactivity. By crossing DNA-specific, or lysozyme-specific immunoglobulin transgenes into these congenic backgrounds, we plan to study how Sle1 and Sle2 impact B-cell tolerance, to these two antigens.
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Significance: These experiments will tell us if the different lupus susceptibility loci breach B-cell tolerance in a global, or (nuclear) antigen-specific manner. Appreciating how the lupus genes tip the delicate balance from tolerance, towards flagrant autoaggression, together with their actual identification, will enrich our understanding of lupus and humor autoimmunity, and pave the way towards more rational and effective therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INHIBITION OF LUPUS NEPHRITIS IN IRF-1 DEFICIENT MICE Principal Investigator & Institution: Reilly, Christopher; Biomedical Scis/Pathobiology; Virginia Polytechnic Inst and St Univ 460 Turner Street, Suite 306 Blacksburg, VA 24060 Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): MRL/Ipr mice spontaneously develop immune complex glomerulonephritis similar to human lupus. Prior to overt disease manifestations, MRL/lpr mice overproduce nitric oxide (NO) secondary to increased gene expression of inducible nitric oxide synthase (iNOS). Blockade of iNOS pharmacologically reduces disease expression in MRL/lpr mice. Both macrophages and mesangial cells respond to IFN-gamma with increased production of iNOS and this response can be potentiated further by the addition of TNF-a. IFN-gamma constitutes one of the most potent macrophage activating factors. Either IFN-7 or IFN-y receptor gene deletion modulates disease activity in lupus mice although other adverse effects in these genetic knockouts were noted. Mesangial cells are the principal immunoregulatory cells in the glomerulus possessing both macrophage and smooth muscle cell characteristics. In addition to expressing Fc receptors, mesangial cells contain receptors that bind cytokines and chemokines including receptors for IFNgamma and TNF-oc. Binding of IFN-gamma to its receptor induces transcription of various genes including IFN-gamma regulatory factor 1 (IRF-1). Many of the inflammatory effects of IFN-gamma in macrophages and mesangial cells are mediated through IRF-1 including up-regulation of IL-12, vascular cell adhesion molecule 1, interferon-p, major histocompatability complex I, and iNOS. The molecular events triggered by IRF-1 activation leading to iNOS expression are not completely elucidated. We hypothesize that IRF-1 plays a key role in the initiation and propagation of the inflammatory response in the murine lupus kidney. Targeting IRF-1 may thus serve as a novel mechanism for blocking inflammation in the lupus kidney. The specific aims described below investigate the role of IFN-y signaling and define the role of IRF-1 in lupus nephritis in MRL/lpr mice. Specific Aim 1: Determine the relationship between IFN-gamma, IRF-1 and NFKB activation on inflammatory mediator production including iNOS, IL-12, COX2, and TNF-c in mesangial cells. We will also determine the effects of specific immune modulators on IFN-y signaling and IRF-1 expression in macrophages and mesangial cells from MRL/lpr IRF-1 (-/-, +/-, +/+), B6 IRF-1 (-/-) and control, wiId type mice stimulated with LPS/TNF-oc. Specific Aim 2: Study the in vivo effect of gene deletion of IRF-1 on MRL/lpr mice by backcrossing C57BL6 (IRF-1- /-) mice onto the MRL/lpr background. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INVESTIGATION INTO THE FUNCTION OF FIG1 Principal Investigator & Institution: Chu, Charles C.; North Shore University Hospital 300 Community Dr Manhasset, NY 11030 Timing: Fiscal Year 2001; Project Start 01-MAR-1999; Project End 28-FEB-2003
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Summary: This proposal is aimed at understanding the function of a recently discovered interleukin-1 (IL-4) induced gene, Figl. Because its expression is regulated by IL-4 and it is only expressed in lymphoid organs, we are particularly interested in understanding its role in immune function. The Figl protein is most similar to the L-amino acid oxidase (LAO) flavoenzyme found in snake venom. Interestingly, LAO kills cells by apoptosis through the production of hydrogen peroxide. Because Figl contains a hydrophobic leader peptide, we propose that Figl is secreted by cells to induce apoptosis of themselves or adjacent cells and thus regulating the immune response. We plan to test this by isolation nd purification of adjacent cells and thus regulating the immune response. We plan to test this by isolation and purification of Figl protein followed by determination if it has similar biochemical properties as LAO. We also plan to heavily explore the role of Figl in the immune system. Besides determination of the ability of Figl protein to induce apoptosis in immune cells, we plan to examine its ability to induce or modify other IL-4 mediated events, especially changes in cell surface protein expression. In addition, we plan to further characterize the expression pattern of Figl in immune cells and confirm whether or not it is a secreted protein. Figl genetically maps to the same region as Sle3, a systemic lupus erythematosus (SLE) susceptibility locus found in mice. Interestingly, some of the characteristics of Sle3 suggest that it may be Figl. Mice with Sle3 have high levels of polyreactive IgM and IgG and a expansion of CD4 T cells. One possible explanation for this phenotype, based on the predicted features of Figl protein, is that mutant Figl protein may not induce apoptosis in activated B cells or in CD4 T cells, resulting in elevated IgM and IgG and an increase in the CD4 T cells. We plan to determine if Figl and Sle3 are identical by genetic mapping in mice and attempting to recreate the Sle3 phenotype by introducing the affected allele into healthy mice. In addition, we plan to extend these studies to human SLE. If we discover that particular Figl polymorphisms are associated with human SLE, we may be closer to understanding some of the genetic basis for susceptibility to SLE. These proposed studies will not only provide new knowledge into the function of a previously uncharacterized protein, Figl, but may also provide exiting new insights into susceptibility to SLE, basic understanding of the development of autoimmunity, and regulation of the immune system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIF MEDIATES ACTH AXIS RESPONSE TO INFLAMMATION Principal Investigator & Institution: Chesnokova, Vera M.; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, CA 90048 Timing: Fiscal Year 2001; Project Start 10-FEB-1999; Project End 31-JAN-2004 Summary: The hypothalamo-pituitary-adrenal axis (HPA) plays an important role in the relationship between the immune and neuroendocrine systems. Blunting of the HPA response to stress enhances susceptibility to or severity of inflammatory/autoimmune disease. The cascade of HPA hormones released under stress conditions may exert a dampening role on specific defense mechanisms, especially on most cellular actions of the inflammatory immune response. Cytokines, polypeptide mediators, classically associated with immune system regulation and inflammation, play a significant role in the HPA axis activation during immune disorders and actively mediate signaling between the immune and endocrine systems. Leukemia inhibitory factor (LIF), a pleotropic cytokine with diverse biologic activities, also present in pituitary corticotrophs, stimulates proopiomelanocortin (POMC) gene transcription, and is significantly induced in mouse hypothalamus and pituitary in response to endotoxin. As LIF is an inducible proinflammatory hypothalamo-pituitary cytokine which may
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function as a paracrine regulator of ACTH we hypothesize that LIF is involved in control of the inflammatory/autoimmune process acting through regulation of the HPA axis. Preliminary studies conducted in LIF knockout mice, and shown herein, demonstrate that in the absence of LIF, mice cannot maintain an appropriate level of HPA axis activation in response to stress and exogenous IL 1. In addition, the low HPA response to mycobacterial adjuvant observed in knockout animals compared to normal littermates shows a strong correlation between LIF-regulated activity of the HPA axis and susceptibility to inflammatory process. In this study we will determine the molecular and physiological mechanisms implicating LIF in the neuroendocrine control of inflammation. We will utilize both in vivo whole animal models as well as in vitro molecular techniques to characterize the role of LIF in mediating HPA axis response to pathological stress. The hypothesis that LIF mediates the HPA axis response to acute inflammatory challenges as well as to experimental (experimental allergic encephalomyelitis) and genetically determined (systemic lupus erythematosus) inflammatory/autoimmune disease will be tested. This study will provide insights into the cytokine-mediated neuro-immuno-endocrine interface. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LUPUS ANTICOAGULANTS AND THE PROTEIN C PATHWAY Principal Investigator & Institution: Esmon, Naomi L.; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, OK 73126 Timing: Fiscal Year 2001 Summary: We have found that the membrane requirements of the APC anti- coagulant complex differ markedly from those of the pro-coagulant complexes, These requirements mimic those of at least a population of autoantibodies found in thrombotic patients, providing both specificity and a link between the APC pathway, lupus anticoagulant/anti- phospholipid antibodies and thrombosis. More recently, we have observed that phospholipid oxidation further enhances APC activity selectively. Oxidation is considered a central feature of many inflammatory diseases including lupus and cardiovascular disease. It is the goal of this application to determine the relationship between the different membrane structural requirements of the prothrombinase and APC complexes with an emphasis on the role of oxidation in these reaction. We will determine whether currently unknown plasma factors are involved in the oxidation, what the active products are and whether any modification to the proteins of the APC complex occur as a result of this oxidation. The lipophilic antioxidant, alpha-tocopherol is regarded as protective against oxidative damage in various diseases, including heart disease. We will determine whether incorporation of tocopherol derivatives in membranes differentially affects the pro- and anti- coagulant reactions which may have direct protective effects against thrombus formation. Patients have been identified whose immunoglobulin inhibits only the oxidation dependent anticoagulant APC activity, while others inhibit the oxidation dependent and independent activity equivalently. It is not known whether these represent different risk groups. Immunoglobulin from thrombotic patients recruited during the first grant period will be screened for the prevalence of anti- APC activity and the binding specificities determined. A chimeric form of protein C whose membrane requirements more closely resemble those of the pro-coagulant complexes will also be used in these studies. We will attempt to correlate APC inhibition and binding patterns with the risk of rethrombosis in the study population to determine whether such classification is useful in the identification of pro-thrombotic antibodies for the diagnosis and/or treatment of thrombosis.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LYMPHOCYTE SIGNALING DEFECTS IN PATIENTS WITH LUPUS Principal Investigator & Institution: Tsokos, George C. Professor of Medicine and Molecular Cell; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, MD 20852 Timing: Fiscal Year 2001; Project Start 15-JUL-1998; Project End 31-MAY-2003 Summary: Systemic lupus erythematosus (SLE) is an idiopathic autoimmune syndrome characterized by disorders of the cellular and humoral immune response that lead to autoantibody production. We have recently demonstrated that lupus lymphocytes display disease-specific, antigen receptor- initiated signaling aberrations and hypothesized that these abnormalities result in altered expression of gene(s) that impair T and B cell immune effector function. The proposed experiments, grouped in 4 specific aims, are based on the finding that lupus T cells display deficient expression of T cell receptor (TCR) zetu chain: 1. We shall test the hypothesis that TCR zetu chain deficiency is disease specific and independent of lupus disease activity. To test this hypothesis we will (a) establish the defective expression of zetu chain in lupus patients and determine its possible association with disease activity, (b) establish whether the defect is limited to lupus, and (c) establish the heritability of the disorder. 2. We shall test the hypothesis that zetu chain is exclusively defective in lupus T cells and that this defect is associated with abnormal phosphorylation of certain cytosolic proteins that are important in T cell signaling. To test this hypothesis we shall determine (a) whether other chains of the CD3 complex and the zetu protein family are deficient in lupus T cells, and (b) which proteins are involved in the increased protein tyrosine phosphorylation that is observed following crosslinking of the CD3 molecule. 3. We shall test the hypothesis that zetu chain deficiency is causally associated with the CD3-initiated hyperphosphorylation of cytosolic proteins in lupus T cells and the increased Ca2+ response. This hypothesis will be tested by (a) establishing an association between the effective expression of the zetu chain and the abnormal CD3- initiated signaling, (b) by transfecting lupus T cells with the zetu chain gene and testing whether successful transfection will reverse the described abnormal cell signaling events, and (c) determining whether the marginally CD3-mediated inositol 1,4,5 trisphosphate (IP3) production increase is due the aberrant phospholipase Cgamma and IP3 receptor phosphorylation. Finally, in the 4th specific aim we will test the hypothesis that zetu chain deficiency is the result of deletion(s) or mutation(s) of the coding or the promoter region of the gene. Experiments will be performed to consider the alternative hypothesis, i.e., zetu chain deficiency in lupus cells is the result of cell activation or other cellular regulatory abnormality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF AUTOIMMUNE RESPONSE IN HUMAN LUPUS Principal Investigator & Institution: Datta, Syamal K. Professor; Medicine; Northwestern University Office of Sponsored Programs Chicago, IL 60611 Timing: Fiscal Year 2001; Project Start 01-AUG-1993; Project End 31-JUL-2005 Summary: (Adapted from the Applicant's Abstract): The long-term goal of this project is to define basic mechanisms of autoimmunity in Systemic Lupus Erythematosus (SLE), by focusing on disease-relevant T helper (Th) cells that induce the production of pathogenic anti-DNA autoantibodies in SLE. The full spectrum of major peptide epitopes, including naturally processed peptide epitopes, for the pathogenic autoantibody-inducing Th cells of human lupus that recognize nucleosomes in a promiscuous manner will be defined. Shared epitopes for autoimmune B-cells of lupus
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will also be identified. Immunologic relevance of the epitopes in influencing autoimmune T- and B-cell functions will be studied. T-cell receptor (TCR) and MHCcontact residues in the peptide epitopes will be finely mapped for finding consensus motifs that could lead to autoantigen -specific therapy of lupus in humans using tolerogenic peptides or altered peptide ligands. Altered peptide ligands that are partial agonists or antagonists will be designed and studied for blocking pathogenic anti-DNA autoantibody production in vitro. Nucleosomal peptide-HLA-DR tetramers (or peptideMHC-Ig chimeric dimers) will be made to track autoimmune T-cells in lupus patients and family members for diagnostic and prognostic purposes, and for studying the effects of peptide tolerogens in vitro. The second part of the project will deal with mechanisms of prolonged hyper-expression of CD40 ligand (CD40L) and resistance to anergy induction and maintenance in T-cells of human lupus. Major components of Tcell signal transduction pathways involved in T-cell activation, and anergy, particularly in the context of CD40L hyper-expression will be defined. The role of differential MAPK activity in CD40L hyper-expression and stability of CD40L mRNA in lupus T-cells will be studied. Possible anomalies in B7-CD28, and CTLA-4 expression and function in lupus T-cells that could lead to the above mentioned defects being analyzed. Identification of critical peptide epitopes for the autoimmune T helper cells of lupus and studies on regulatory defects in expression of co-stimulatory signaling molecules are leading towards an understanding of basic mechanisms of the disease and development of specific immunotherapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF GP120 CLEAVING ANTIBODIES IN LUPUS Principal Investigator & Institution: Tramontano, Alfonso; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, TX 77225 Timing: Fiscal Year 2001 Summary: Antibodies (Abs) with innate proteolytic activity are detected in the mouse and human autoimmune repertoires. Antibodies in human SLE and in a murine lupus model (MRL/lpr) have also been shown to bind HIV-1 antigens with high affinity. The central hypothesis of this proposal is that specific catalytic Abs against HIV-1 gp120 could be expressed in subjects with autoimmune disease. Such antibodies may have therapeutic potential for inactivation of HIV-1 infectivity through specific proteolysis at viral capsid sites. Molecular studies suggest that a serine protease-like active site at or near the antigen binding site of peptidase Abs is encoded by a germline VL gene. Our proposal will explore the occurrence, molecular specificity and biological activity of HIV- 1 gp120-specific Ab proteases that arise in autoimmunity. A variable domain (Fv)phage library, constructed from antibody genes found in human SLE is expected to comprise both catalytic and gp120-specific antibodies. Proteolytic Ab fragments from the phage display libraries will be obtained by chemical selection, using active sitemodifying reagents for specific covalent labeling and affinity capture of Abs with serine protease-like reactivity. A series of reagents having a common reactive group and differing degrees of analogy with the target substrate (gp120) will be compared for their relative efficacy in capturing specific and catalytically efficient Abs from the library. These studies will also examine if proteolytic degradation at specific gp120 sites, including a neutralizing epitope for conventional antibodies leads to more effective inactivation of the virus. The range of binding specificities in the lupus repertoire suggests that broadly inactivating catalytic Abs are likely to be identified. Insights from the mechanistic studies shall be integrated into the studies of the comparison proposals of the program project application. The overall Program Project has significant
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implications for development of a new therapeutic modality for treatment or prevention of HIV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF CD40 SIGNALING IN B LYMPOCYTES IN VIVO Principal Investigator & Institution: Noelle, Randolph J. Associate Professor; Microbiology and Immunology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Humoral immune and autoimmune responses are governed by the interactions of CD154 expressed on helper T cells and CD40 on B cells. Extensive efforts have been made to unravel how CD40 engagement transduces the diversity of signals to trigger B cell expansion and differentiation. Like many of the other TNF Receptor family members, it is believed that the recruitment of TNF Receptor Associate Factors (TRAFs) to the cytoplasmic domain of CD40 plays a critical role in regulating CD40 biology. This proposal focuses on the role that TRAFs, and other signaling elements play in regulating B cell function in vivo. We present a unique cohort of Tg/knock-out mice that express mutations in the cytoplasmic tail of CD40 which disrupt the interaction of the cytoplasmic domain with specific TRAFs. B cells from these mice will be studied in vitro (Specific Aim #1) and in vivo (Specific Aim #2) to address the causal relationships between signaling domains of the cytoplasmic tail of CD40 and the induction of in vitro and in vivo B cell biochemistry and function. Preliminary data shows that the loss in TRAF recruitment in B cells exerts minimal or no impact on early IgM and lgG responses in vivo, however, a major effect of TRAF recruitment is observed on the durability of humoral immune responses in vivo. While loss in TRAF recruitment results in defined lesions in humoral immunity, many aspects of the humoral immune response are intact in the absence of TRAF recruitment. We propose to identify (Specific Aim #3) non-TRAF binding domains in CD40 that are critical for early B cell activation. Genetic and proteonomic approaches are presented that will identify novel, functionally significant sites in the CD40 tail and the factors they bind. Enhanced TRAF recruitment and chronic CD40 signaling in the B cell compartment is believed to contribute to the development of lupus. We propose that the expression of a constitutively active form of CD40 (CD40zip; a leucine-zippered, myristoylated CD40 tail), within the B cell compartment will drive B cell expansion and differentiation in vivo and result in the development of a lupus-like syndrome (Specific Aim#4). Assuming the development of autoimmunity in Tg CD40zip mice, mutations in the TRAF binding sites of CD40zip, will be engineered to evaluate the contribution of specific TRAFs to the development of autoimmunity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF DEFICIENT PKAII ACTIVITY IN LUPUS T CELLS Principal Investigator & Institution: Shanks, Ryan A. Internal Medicine; Wake Forest University Health Sciences Winston-Salem, NC 27157 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by the applicant): Systemic lupus erythematosus (SLE) is an idiopathic autoimmune disorder of indeterminate etiology characterized by the T cell's inability to carry out programmed physiological immune effector functions, including help and cytotoxicity. Our laboratory identified the first disorder of T cell signaling involving the cAMP/protein kinase A (PKA) pathway. There is a profound deficiency of
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PKA phosphotransferase activity due to diminished type I (PKA-I) and type II (PKA-II) isozyme functions. Deficient PKA-II activity is associated with abnormal nuclear translocation of the beta isoform of the regulatory subunit from the cytosol and its retention in the nucleus. I hypothesize that nuclear RII beta-subunit in SLE T cells is a transcriptional repressor of the c-Fos gene. RII beta-subunit is predicted to bind to the nuclear transcription factor, cAMP response element binding protein (CREB), preventing CREB form binding to the cAMP response element (CRE) of the c-Fos gene and thereby inhibiting the gene's transcriptional activation. Transcriptional repression of c-Fos indirectly diminishes the generation of IL-2. This mechanism may contribute to impaired IL-2 production by SLE T cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF DRUG INDUCED LUPUS Principal Investigator & Institution: Yung, Raymond L. Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-MAY-2004 Summary: The application proposes funding with the specific intent of developing an independent research program by the principal investigator. For the past three and a half years, the applicant has been pursuing his interest in basic science research in the areas of T cell immunology and pathogenesis of lupus. Both the clinical and basic science training have prepared the applicant for an independent career in academic rheumatology/immunology in the near future. The proposal is a natural extension of the applicant~s current research. The applicant has shown that murine Th2 cells overexpress LFA-1 (CD11a/CD18) and become autoreactive following treatment with two distinct DNA hypomethylating agents. Adoptive transfer of these autoreactive cells will also induce a lupus-like disease in syngeneic mice. This proposal will first examine the relationship between different lupus-inducing drugs and T cell DNA hypomethylation. The role of LFA-1 in T cell autoreactivity and in vivo autoimmunity will be determined by overexpressing LFA-1 on T cells directly through transfection of murine LFA-1 constructs, and the use of ICAM-1 deficient mice in the murine system. The role of Th1 and Th2 cytokines in T cell autoreactivity in vitro and autoimmunity in vivo will also be examined. Finally, attempts will be made to knockout the murine T cell DNA methyltransferase gene by homologous recombination to definitively determine the role of the gene in the proposed hypothesis of environmental agents inhibiting T cell DNA methyltransferase , leading to DNA hypomethylation, LFA-1 overexpression, and T cell autoreactivity and in vivo autoimmunity. The murine model is likely to have relevance to human disease, as abnormal T cell DNA methylation, LFA-1 overexpression, and increased production of Th2 cytokines such as IL-6 have all been reported in human lupus patients. The application is now in the position to develop his own independent research program as a junior faculty member in the Department of Internal Medicine. It is expected that the applicant will be promoted to a tenure track position during the time of the award. The sponsor, Dr. Bruce Richardson, who is also head of the division of Rheumatology at the Ann Arbor Veteran Administration Hospital, is commited to contributing protected time and resources to the applicant. The collaborators, Dr. Rossler and Dr. Johnson, as well as the core facilities at the University of Michigan will also provide expert help where it is needed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF IMMUNE TOLERANCE INDUCED IN MURINE LUPUS Principal Investigator & Institution: Hahn, Bevra H. Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 15-FEB-2000; Project End 31-JAN-2004 Summary: This proposal aims to define mechanisms of T cell tolerance induced in vivo in NZB/NZW F1 lupus-like mice lupus by administration of a novel, artificial peptide (consensus peptide, pCONS). Tolerance results in dramatic delay in appearance of high titer IgG anti-dsDNA and nephritis, and prolongs life 7 months or more. PCONS is constructed from an algorithm based on spontaneous proliferation of BWF1 T cells to wild peptides from the VH regions of BWF1 monoclonal antibodies to DNA. The algorithm predicts amino acid sequences likely to stimulate BWF1 T cells. A wild peptide (p33B) sharing 10 of 15 amino acids with pCONS, representing a sequence in the VH region (CDR1/FR2) of a mAb BWF1 IgG2a anti-dsDNA, has similar effects. Treatment with an artificial peptide that violates the algorithm, pNEG, produces no clinical benefits. Mice treated with pCONS or p33B, but not saline or pNEG, have reduced proliferation of T cells to immunization with the tolerizing peptide, and reduced T cell help for production of IgG anti-dsDNA in vitro. They also fail to develop the high plasma levels of IFN (and IL-4 that characterize saline-treated BWF1 females. We hypothesize that the large effects of these tolerogens result from induction of apotosis, cytokine deviation, or both in a large population of helper T cells - possibly a population that recognizes different peptides from multiple autoantigens, either early in life or later, after determinant spreading. These effects may correlate with affinity and stability of peptide/MHC Class II binding. The hypothesis will be tested by determining peptide/Class II binding affinities and stability (including peptide variants), developing surrogate rapid measures of effects on BWF1 T cells that predict clinical efficacy of peptides with different MHC binding characteristics, determining the effect of peptide/MHC engagement of TCR on T cell survival and cytokines, and testing peptide variants in vivo for clinical effects. Differences between the T cell responses to peptide/MHC complexes in BWF1 and normal mice expressing the MHC Class II molecules restricting these peptides, will identify novel characteristics of Th activation that characterize the autoimmune mice. Since patients with SLE have T cells that recognize Ig-derived peptides from human monoclonal antibodies to DNA, the information from these experiments may suggest a novel therapeutic approach to this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF T-CELL INDUCED-APC CYTOTOXICITY IN LUPUS Principal Investigator & Institution: Kaplan, Mariana J. Assistant Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The application requests funding with the specific intent of developing an independent research program by the principal investigator. The applicant has been pursuing basic science research in the areas of T cell immunology and pathogenesis of lupus (SLE) for the past four years. The proposal is an extension of the applicant's current research on monocyte/macrophage (M theta) apoptosis. Hypothesis: Apoptosis-inducing molecules mediate the autologous monocyte/M theta
78 Lupus
killing caused by CD4+ lupus T cells. Target cell killing by this mechanism can lead to the generation of autoantibodies. Specific aims: To determine the pathways involved in monocyte/M theta apoptosis induced by lupusCD4+ T cells. The applicant will test whether it's possible to inhibit the development of autoimmunity in an SLE animal model, by blocking the apoptotic pathways involved in monocyte/M theta killing by autoreactive CD4+ T cells. The role of macrophage apoptosis in triggering or augmenting autoimmunity will also be investigated. Methods: a) Measurement of cell surface expression of death-receptor ligands on SLE and control T cells by flow cytometry. b) With cytotoxicity assays, determine whether these apoptotic pathways are functional in SLE monocytes/M theta and whether blocking these molecules can inhibit the autologous monocyte/M theta killing by SLE T cells. c) Given the redundancy of the pathways involved in M theta cytotoxicity, the applicant will test, in vitro, if inhibiting the death signals downstream of the death receptors (FADD, caspases, FLIP) is sufficient to inhibit monocyte/M theta apoptosis induced by these ligands. d) In vivo studies will try to characterize whether the blockade on monocyte/macrophage death-receptor ligands by monoclonal antibodies or fusion proteins, can inhibit the development of murine SLE, and whether the elimination of tissue macrophages; per se (with clodronate liposomes in vivo) is sufficient to induce autoimmunity in an animal model. The results of the studies proposed might identify potential mechanisms involved in the generation of autoantigens in SLE. These could lead into the development of therapeutic interventions designed to reverse these abnormalities and abrogate or block the onset and severity of this disease. The sponsor and the institution are committed to contributing protected time, career development and resources to the applicant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MIDCAREER INVESTIGATOR AWARD IN PATIENT-ORIENTED RESEAR Principal Investigator & Institution: Brey, Robin L. Professor; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2007 Summary: (provided by the applicant): Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease that affects predominantly young, minority, pre-menopausal women. Up to 75% of patients with SLE experience some type of nervous system manifestations during their disease course (termed neuropsychiatric lupus or NPSLE). The most common manifestations include cognitive dysfunction, psychiatric disease and stroke, although the full range of NS involvement has not been well characterized. Two major areas of the candidate's research have been the study of 1) clinical and serologic predictors for the development of NPSLE, and 2) immune-mediated thrombosis related to antiphospholipid antibodies (aPL). The major thrust of this proposal will be to expand a strong clinical research program studying NPSLE in a cohort of predominantly Mexican-American SLE patients by 1) determining the frequency of and risk factors for accelerated atherosclerosis in this well-defined cohort and 2) evaluating the frequency and of microembolic signals (MES) by transcranial doppler (TCD) and the relationship between MES and cerebrovascular ischemia and cognitive dysfunction in 2 cohorts of SLE patients (UTHSCSA and Dusseldorf, Germany) with and without aPL. SLE patients are at increased risk for thrombotic events, including both myocardial infarction and stroke. Several NPSLE manifestations may have cerebral ischemia as a common underlying pathophysiologic mechanism, e.g. cognitive dysfunction and stroke. Potential causes of ischemia in SLE include vasospasm, microvascular disease, thrombosis with or without atherosclerosis,
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and rarely, vasculitis. The frequency of atherosclerosis in SLE, the importance of atherosclerosis in SLE-related stroke risk, or whether there are important genetic or racial influences are unknown. Traditional vascular risk factors, inflammatory, immunological, and treatment-related factors specific to SLE are all likely to be involved. With the support of the Mid-Career Investigator Award, the candidate will work with a multidisciplinary team of established investigators and fellows in the areas of stroke, vascular and brain imaging, immunogenetics, epidemiology, psychiatry and neuropsychology. This collaborative effort will provide very important information regarding prevalence and extent of sub-clinical vascular disease and associated risk factors in SLE. Much will be learned about the relative importance of genetic factors and autoantibodies on vascular disease risk in SLE that is likely to apply to other populations also at increased risk for cerebral ischemia and vascular dementia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR RECOGNITION OF DNA BY AUTOANTIBODIES Principal Investigator & Institution: Glick, Gary D. Professor; Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2002; Project Start 01-AUG-1992; Project End 28-FEB-2006 Summary: (provided by applicant): Autoantibodies that bind DNA (anti-DNA) are a hallmark of the autoimmune disorder systemic lupus erythematosus (SLE). A subset of anti-DNA are pathogenic: they mediate an inflammatory response in kidney tissue resulting in renal damage. During the previous project period, we studied the thermodynamic basis of sequence-specific binding by anti-ssDNA mAb 11F8. These studies were predicated on the observations that 11F8 is pathogenic; injecting hybridoma cells that produce 11F8 into normal mice results in nephritis of a nature and severity similar to that seen in human lupus, and the ability of 11F8 to cause disease is linked to its DNA binding properties. In a second research area, we identified a new benzodiazepine (1) that is pro-apoptotic. This compound is remarkably effective in treating the lupus-like disease in the two most clinically relevant polyclonal animal models of SLE. Significantly, treatment is not accompanied by the broad toxicities and side-effects that plague current therapeutic regimes. Based on these findings, the next phase of this grant proposes a series of basic and translation experiments that could directly impact our understanding of the pathology of lupus and the way in which this disorder is diagnosed and treated: (a) Investigate structural aspects of 11F8 recognition through X-ray crystallography, fluorescence resonance energy transfer experiments, and functional group mutagenesis of the 11F8 consensus sequence (Aims 1-2); (b) Use stopped-flow kinetics to investigate the mechanism by which 11F8 discriminates between specific and non-specific ligands (Aim 3); (c) Revert somatic mutations in 11F8 back to germline residues through site-directed mutagenesis to explore the functional significance of affinity maturation in the evolution of the autoimmune response to DNA (Aim 4); (d) Evaluate the utility of the 11F8 consensus sequence (SEL11F8) as a diagnostic probe for lupus (Aim 5); and (e) Use combinatorial chemistry to identify analogs of 1 possessing increased potency in vitro, and test these molecules in vivo (Aim 6). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MURINE MODELS OF GENERALIZED AUTOIMMUNITY Principal Investigator & Institution: Theofilopoulos, Argyrios N. Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000
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Timing: Fiscal Year 2001; Project Start 01-APR-1983; Project End 31-AUG-2002 Summary: Systemic lupus erythematosus is a complex, largely genetically-determined, disease with T and B cell tolerance defects leading to autoantibody production against a wide array of self-molecules. Normal T and B cell tolerance occurs centrally or peripherally either as clonal deletion or anergy. Clonal deletions are mediated by apoptosis, a process controlled by an intricate web of promoting and inhibition genes, while the molecular events underyling anergy are unknown. Whereas immature lymphocytes rapidly undergo apoptosis in response to receptor-mediated signals, death of mature cells requires entry into cell cycle, a process also controlled by multiple promoting and inhibiting genes. The relevance of defective activation-induced apoptosis in systemic autoimmunity has been highlighted by the discovery of mutations in the FAS/FASL system in mice with lymphoaccumulation/lupus syndromes. Based on the documented importance of these processes in the induction of tolerance, the central hypothesis in this proposal is that the lupus-associated tolerance defects must be reflected directly or indirectly in the cell-cycle and apoptosis programs, and that detailed analysis of these systems will be instrumental in understanding the etiology of this disorder. This hypothesis will be addressed in the first specific aim by examining activation-induced cell cycle and apoptosis of T and B cells from unmanipulated lupus mice. Expresison levels of the multiple cell cycle-and apoptosis-controlling genes will be measured and correlated with functional and clinical assessments. Emphasis will be given to validating the hypothesis that accumulation of apoptosis-resistant memory T cells in lupus mice is caused by cell cycle arrest. Associated with increased levels of cyclin kinase inhibitors. In the second specific aim, lg transgenic normal and lupus background mice will be used to define mechanisms of B cell tolerance as reflected in cell cycle and apoptosis genes, and to test the hypothesis that lupus mice differ from normals in B cell responses to antigen and memory B cell generation. In the third specific aim, T cell tolerance will be similarly characterized in T cell receptor transgenic normal and lupus mice under conditions leading to activation, anery or deletion. Additional studies using reciprocal adoptive transfers will test the influence of environment on generation and survival of membory T cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MUTATIONS IN PKA GENE TRANSCRIPTS OF LUPUS T CELLS Principal Investigator & Institution: Laxminarayana, Dama; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, NC 27157 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) is an idiopathic autoimmune disorder of indeterminate etiology with multiple Immune effector dysfunctions, which afflicts females in the child bearing years. Protein kinase A (PKA) plays an important role in regulation of immune effector functions of T cells. Previous research has revealed a disorder of type I protein kinase A (PKA-I) enzyme activity in SLE T cells. Recently the applicant has identified mRNA transcript editing of PKA-I RIalpha-subunit and up-regulation of the transcript editing gene, adesosine deaminases that acts on RNA (ADAR) in SLE T lymphocytes. The RNA editing is the co- or posttranscriptional modification of RNA molecules, which results in the insertion, deletion or substitution of nucleotides, mRNA editing plays an important role in the regulation of gene expression and produces phenotypic variability by diversifying the information encoded within the corresponding genomic sequence. The objective of this proposal is to identify the molecular mechanism(s) leading to mRNA transcript editing in RIalphaand RIbeta-subunits of PKA-I and their role in deficient PKA-I isozyme
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phosphotransferase activity in SLE T lymphocytes. The specific aims of the project are;(1) to quantify mRNA transcript editing in RIa and RIbeta gene transcripts in T cells from patients with SLE and compare this with normal controls as well as patients with rheumatoid arthritis (RA) to characterize its association with SLE pathogenesis;(2) to characterize mutant RIa- and Ribeta-subunit proteins phosphotransferase activity in T cells from SLE patients;(3) to analyze regulation and expression of the ADAR gene in T cells from normal, RA and SLE patients and determine whether there is a selective association with SLE pathogenesis;(4) to quantify ADAR-mediated adenosine to inosine conversion in controls and SLE lymphocyte gene transcripts; and, (5) to quantify ADAR2 transcript editing in T cells of SLE patients and compare this with that in T cells of normals and RA patients to characterize its association with SLE pathogenesis. Therefore, the major goal of this project is to identify RNA editing events in the gene transcripts of SLE T cells and the subsequent dissection of editing mechanisms. The novel data derived from these experiments will prove crucial in addressing questions of functional, biological significance, and regulatory events responsible for deficient PKA-I isozyme phosphotransferase activity in SLE T lymphocytes. Identification of this new mechanism of transcript mutations will provide new insights into the mechanisms of aberrant T cell immune effector functions in SLE and open a new avenue of research to design molecular tools to control aberrant immune functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEPHRITIS LINKAGE IN LUPUS Principal Investigator & Institution: Quintero-Del Rio, Ana I.; Oklahoma Medical Research Foundation Oklahoma City, OK 73104 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Renal disease occurs in up to 75% of the systemic lupus erythematosus (SLE) patients usually appearing shortly after diagnosis. We recently linked a putative susceptibility gene to 10q22.3, which leads to lupus in nephritis related lupus families of European American background (1). Our goal for this proposal is to narrow the susceptibility region and to identify the susceptibility gene. We will achieve this by iterative reduction in the size of the chromosomal region. First, we will choose microsatellite markers to form a 1-2 cM map across the current susceptibility region and analyze these data using genetic linkage methods. Second, we will choose single nucleotide polymorphism (SNP) markers to form a 0.5 cM map across the reduced region and analyze these data using linkage disequilibrium methods. In the final step, we will search the public databases for SNPs in genes known to be located in the narrowed susceptibility region previously established and to analyze these using linkage disequilibrium methods. If this does not locate the functional mutation then the gene will be sequenced to find the causal mutation(s). Since autoimmune diseases are thought to share some of their genetic origins, we ascertained families multiplex for SLE in which at least one affected was diagnosed with nephritis, with the intent of decreasing sample heterogeneity and increasing the power to identify the susceptibility gene(s). Our preliminary results support the hypothesis that SLE and nephritis may share common genetic determinants in families of European American background (1). This project is directly relevant to the goals of NIAMS small grant program for new investigators and has the potential to reveal important, previously unappreciated, susceptibility genes, which contribute toward understanding the etiology of SLE and nephritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEPRESSION
NEUROPSYCHOLOGICAL
TESTING
FOR
LUPUS
AND
Principal Investigator & Institution: Kozora, Elizabeth; National Jewish Medical & Res Ctr and Research Center Denver, CO 80206 Timing: Fiscal Year 2001; Project Start 20-JUL-2001; Project End 30-JUN-2003 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which is characterized by multi-system involvement and diverse manifestations. A large fraction of patients with SLE demonstrate organic psychiatric and neurologic disorders indicating central nervous system (CNS) involvement and the prevalence of cognitive abnormalities is approximatley 50 percent. An ad hoc multidisciplinary Committee of 35 members was convened by The American College of Rheumatology Research Committee in April of 1997 for the purpose of developing standard nomenclature for neuropsychiatric SLE and proposed a standard battery of neuropsychological tests for SLE This study was designed to provide validity and reliability for this proposed short battery. Pilot data by this investigator has suggested that diagnostic categories are complicated by a large proportion of systemic lupus erythematosus (SLE) patients being categorized as CNS-SLE (Central Nervous SystemSLE) due to symptoms of depression. We see these preliminary data as providing controversy and ultimately opportunity to better classify and understand the cognitive effects of depression in SLE. Information regarding the sensitivity and specificity of this type of battery will justify the use of a short battery for clinical evaluation in SLE, in SLE patients with depression, and potentially in patients with depression only. Specific Aims are 1) To compare the frequency of neuropsychological impairment in CNS-SLE, CNSSLE-depressed, non-CNSSLE and normal controls using the proposed American College of Rheumatology (ACR) Repeatable Neuropsychological Battery for SLE (ACR-RNBSLE); 2) To examine the frequency of SLE patients impaired on the ACR-RNB-SLE compared to a larger comprehensive battery; 3) To determine reliability of the proposed ACR-RNB-SLE; 4) To examine associations between performance on the ACR-RNB-SLE and proposed measures of depression, fatigue and pain; and 5) To compare cognitive performance of the CNS-SLE-depressed group to a control group of depressed-only patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NIAMS CLINICAL RESEARCH CENTER FOR RHEUMATOID DISEASE Principal Investigator & Institution: Silver, Richard M. Professer; Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The Medical University of South Carolina will establish a Multidisciplinary Clinical Research Center (MCRC) for the Study of Rheumatic Diseases in African-Americans. This MCRC will focus on scleroderma (SSc) and systemic lupus erythematosus (SLE), two rheumatic diseases that disproportionately affect the African-American community. Outstanding leadership in three key areas - Rheumatology, Biometry/Epidemiology, and Health Services Research - provides a framework for successful design and implementation of meaningful clinical research in this understudied population of patients. Three projects and three supporting cores are proposed. Project A is designed to study the interactions between TGF-beta and sphingolipid signaling pathways in SSc and normal fibroblasts. The proposed studies will elucidate this heretofore-unknown interaction to shed light on the
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mechanism whereby TGF-beta signaling is integrated with other cellular signaling pathways leading to fibrosis. Project B addresses an important understudied area, namely psychosocial aspects of female adolescents with SLE, the majority of whom are African-American. MCRC investigators will assess the associations between adaptational processes and adjustment and health-related quality of life, and will conduct an interventional trial designed to enhance adjustment and quality of life for these patients. Project C will address the important issue of divergent racial trends in morbidity from lupus nephritis. Mortality has increased for African-American lupus patients while remaining stable in Caucasian lupus patients, and this divergence cannot be accounted for by differences in socioeconomic status alone. Utilizing the unique resources of the Carolina Lupus Study and the sea island Gullah population, MCRC investigators will address genetic and environmental influences on the development and progression of lupus nephritis. Each of these projects, as well as future pilot projects to be developed by the MCRC, will be served by two Cores: (1) a Methodology Core will provide rigorous methodological and biostatistical support; and (2) a Patient Resource Core will assure MCRC investigators access to a population of African-American patients who are clinically well characterized and from whom biological samples are obtained and stored. This MCRC will facilitate the translation of basic research into the clinical arena, support much needed behavioral research, and conduct epidemiology and health services research on rheumatic diseases affecting minorities and women disproportionately, thus exemplifying the "cross-cutting" nature of research proposed in NIAMS's strategic plan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NITRIC OXIDE AND SYSTEMIC LUPUS ERYTHEMATOSUS Principal Investigator & Institution: Gilkeson, Gary S. Professor; Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 23-APR-1999; Project End 28-FEB-2003 Summary: Nitric oxide (NO) is a biologically pluripotent compound that is induced during immune responses and overproduced in murine models of lupus. We have found in murine lupus: 1) pharmacologic blockade of NO production ameliorates lupuslike disease, 2) nitration of tyrosine residues of several proteins including catalase with alternations in catalase function in the kidney, and 3) increased levels of NO in the spleens modulate splenocyte apoptosis. In our retrospective studies of human lupus, serum measures of NO (serum nitrate) correlated with clinical disease activity, although there was overlap between normals and lupus patients which may reflect effects of dietary nitrate intake. To definitively determine NO production in human lupus compared to controls and the effects of NO in disease pathogenesis, we propose a prospective study of lupus patients and murine studies to provide insight into immune factors promoting NO production in disease. These studies are incorporated in the following specific aims: 1. Prospectively follow 70 lupus patients with primarily early disease monitoring disease activity and systemic NO production via serum nitrate/nitrite and 3nitrated proteins quarterly for 3 years. 2. A. Measure apoptosis of PBMCs in lupus patients and controls both in vivo and in vitro, correlating apoptosis with disease activity and NO production. B. Determine NOS2 expression in human lupus kidneys and correlate NOS2 expression with disease class, activity, and chronicity. C. Identify serum factors in lupus sera that stimulate NO production by PBMCs. D. Identify human lupus serum and kidney proteins that are nitrated using mass spectrometry analysis. 3. A. Using genetically deficient mice, we will determine the role of immunoglobulin, C3, complement factor B, and CD40 in macrophage
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activation and NO production in MRL-lpr mice. B. We will assess if L-NIL, a specific inhibitor of NOS2, is effective in preventing lupus-like disease in MRL-lpr mice. C. We will determine if estrogen modulates NO production in MRL-lpr mice using ovariectomy studies and estrogen receptor knockout mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL PROTEINS ASSOCIATED WITH SS-A/RO IN TARGET ORGANS Principal Investigator & Institution: Chan, Edward K. Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2001; Project Start 01-MAR-2001; Project End 28-FEB-2006 Summary: (Verbatim) Autoantibody reactivity with the SS-AIRo antigen is an important clinical serological marker for SLE, Sjogren's syndrome, subacute cutaneous lupus erythematosus and neonatal lupus erythematosus (NLE). Two cellular proteins, 60 and 52kDa, have been identified as the predominant targets of the autoimmune response. The long-term objectives of the current proposal are to understand both the origin of this specific autoreactivity and the cellular function of the cognate antigens. Such knowledge should provide critical insights into the pathogenesis of the associated diseases that may differ for each clinical phenotype. Recently a novel 75kDa phosphoprotein (pp75) has been identified as an interaction partner for the 6OkDa SSAIRo protein. In addition it has been identified as an autoantigen recognized by antibodies in sera from patients with Sjogren's syndrome and mothers of children with NLE. Accordingly, three Specific Aims are designed to examine the overall significance of SS-AIRo autoantibodies in the four disease entities and to evaluate if any candidate protein partner(s) of SS-AIRo may provide new clues to the autoimmune pathogenesis. Aim 1 will focus on the identification of pp75 and further define its relationship with 6OkDa SS-A/Ro. Additional experiments will examine whether pp75 is associated with additional proteins. Aim 2 will explore the association of SS-AJRo antigens with other tissue-specific and ubiquitously expressed proteins in the skin, heart, and salivary glands using yeast two-hybrid screen with respective cDNA libraries. The rationale is that each of the target organs may have unique proteins which are available to interact with SS-A/Ro proteins. Differences and similarities among interactions defined in the three affected organs should be highly informative. Aim 3 will address the prevalence of anti-pp75 and antibodies to other putative tissue-specific candidate interaction partners in sera from the four disease groups. Clinical correlations will strengthen the relationship of the antibodies to the pathogenesis of tissue injury. The proposed studies will significantly advance our current understanding of the SS-AIRo antigen/antibody system and its functional role in disease states which target specific organs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OKLAHOMA SPECIALIZED CENTER OF RESEARCH IN SLE Principal Investigator & Institution: Reichlin, Morris; Vice President of Research; Oklahoma Medical Research Foundation Oklahoma City, OK 73104 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The Oklahoma Medical Research Foundation proposes a Specialized Center of Research (SCOR) in systemic lupus erythematosus which will focus on understanding the roles of autoantibodies in SLE. The overarching goal of this center will be to integrate clinical rheumatic disease research with basic science investigators from throughout campus thereby strengthening basic science and
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patient oriented research in this state. Dr. Morris Reichlin is the Director, and he brings a distinguished career's worth of rheumatic disease research activities to this new integrated program. Briefly, this SCOR has five key investigators, five collaborating investigators (in-state), five collaborating investigators (out-of-state), nine additional arthritis investigators, fourteen basic science investigators, a Data and Analysis Core Director, Advisory Committee and a host of adjunct faculty, post-doctoral fellows, clinical fellows, MD-PhD students and graduate students. The key projects for this proposal include various approaches to understand how autoimmune responses start in SLE and how autoantibodies could lead to pathogenesis. The major projects in this SCOR will focus on understanding the development of autoantibodies with regards to symptom and SLE disease onset, exploring the role of autoantibodies in the development of dyslipidemias and accelerated cardiac disease, evaluating the basic role of B cell tolerance in the accrual of lupus autoantibodies, identifying potential etiologic triggers of these aberrant autoimmune responses and assessing the genetic predisposition to a severe serological and clinical SLE phenotype. A Data and Analysis Core and Administrative Core will support each of these individual projects. The primary Oklahoma SLE SCOR objectives are fourfold. First, this SCOR will strengthen research through integration of basic and clinical science in finding key etiological factors for SLE by supporting the above mentioned research projects. Second, biostatistical/research design issues will be incorporated into all ongoing rheumatic disease research in order to raise the current level of research activity. Third, key unique patient resources will be shared by several of the projects. Finally, this SCOR will provide a multidisciplinary structure and resources to strengthen current clinical rheumatic disease research through the influence of strong basic scientists involved in cardiovascular biology, lupus genetics, inflammation, coagulation, molecular biology, immunobiology, immunogenetics, clinical pharmacology and protein studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OMEGA 3 LIPIDS AND CALORIES EFFECT ON SLE AND AGING Principal Investigator & Institution: Fernandes, Gabriel I. Professor; Medicine; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, TX 78229 Timing: Fiscal Year 2001; Project Start 15-APR-1998; Project End 31-MAR-2003 Summary: The autoimmune prone NZBxNZW F1 (B/W) mouse is a useful model of systemic lupus erythematosus (SLE). Moderate calorie restriction (CR) delays the onset of disease and doubles the life span of these animals. Both CR and diets enriched in fish oil ((w-3) fatty acids decrease inflammatory cytokines, maintain (CD4+ CD44Low) T cell subsets and prevent the rise of memory (CD4+/CD44High) T cells with age. The involvement of Th-1 and Th-2 T cells subsets in the pathogenesis of murine (and probably human) lupus raises the question of whether CR and w-3 supplementation produce their effects by modulating anti- inflammatory cytokines. We propose that CR delays differentiation of CD44High T cells into Th-0, and/or Th-1 and Th-2 subsets by maintaining higher levels of adrenocorticosteroid (CORT) levels and apoptosis. In addition w-3 lipids and CR may also influence co-stimulatory molecules by increasing expression of antioxidant enzymes and reducing chronic oxidative stress. We propose that supplementation with w-3 fatty acids combined with CR maintains a youthful immune system by decreasing formation of free radicals and inflammatory cytokines and decreasing B cells autoantibody production. We hypothesize that CR delays formation of Th-1/Th-2 subsets by co-stimulatory interaction including lowering CD40 ligand expression and by normalizing apoptosis in both lymphoid cells and target tissues. Studies in specific aim 1 will determine if corn oil vs. fish oil lipids with and
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without CR affect the differentiation pathways and functional activity of Th-1 and Th-2 cells by modulating the interaction between CD28/CTLA-4 and B7-1/B7-2 costimulatory molecules in CD4+ T cells and B cells. Experiments in specific aim 2 will determine if prolongation of life span by w-3 fatty acids and/or CR is accompanied by increased anti-CD3 or dexamethasone induced apoptosis in thymic and splenic cells. Studies in specific aim 3 will determine whether prolongation of lifespan by w-3 fatty acids and/or CR is accompanied by decreased autoantibody production in B/W mice. In summary, our studies will examine whether w-3 fatty acids combined with moderate CR can further ameliorate autoimmune disease in B/W mice. These studies are especially important in view of the significant rise in the consumption of vegetable oils in recent years which may promote obesity and autoimmune disorders in the USA. In contrast, the anti-inflammatory w-3 fatty acids are consumed in negligible amounts. It is possible that moderate dietary changes will delay the onset of autoimmune diseases as well as significantly decrease the required doses of cytotoxic and immunosuppressive drugs normally used to treat SLE and other autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MINORITIES
OUTCOME
OF
SYSTEMIC
LUPUS
ERYTHEMATOSUS
IN
Principal Investigator & Institution: Lisse, Jeffery R.; University of Texas Medical Br Galveston 301 University Blvd Galveston, TX 77555 Timing: Fiscal Year 2001 Summary: Systemic Lupus Erythematosus(SLE) is relatively common disease that presents with several different features. It is more prevalent in women and may be more prevalent and severe in African American and Hispanics. This study will determine whether socioeconomic and ethnic factors influence genetic factors that contribute to the development of SLE. Caucasians, Hispanics and African Americans with SLE for less than 5 years at entry will be recruited into the study. Demographic, socioeconomic and cultural features will be recorded. Laboratory findings will be followed. Disease outcome as manifested by number and severity of flares, responses to standardized questionnaires, over all functional status, kidney function and length of survival will be followed for 5 years. The study will contribute to out understanding of the impact of genetic associations on the outcome of SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOGENESIS OF MURINE LUPUS NEPHRITIS Principal Investigator & Institution: Richards, Hanno B. Assistant Professor; Medicine; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by candidate): Systemic Lupus Erythematosus (SLE) is an autoimmune disease of uncertain etiology that is influenced not only by genetic but also by environmental factors. Particularly the latter remain poorly understood. Development of nephritis is a prominent feature in SLE, contributing substantially to morbidity and mortality. Present treatment options for nephritis are limited and associated with significant toxicity. Better understanding of the pathogenesis of renal disease in SLE may lead to the development of new, less toxic therapies. Pristane injected intraperitoneally (i.p.) into mice genetically not prone to autoimmune disease induces the production of lupus specific autoantibodies, including antiDNA/chromatin, and immune complex nephritis. In preliminary studies we have found
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that IFNg and IL-6 are essential for both the production of these antibodies and the nephritis, but that nephritis may develop prior to the antibody response. We hypothesize that anti-DNA/chromatin autoantibodies are a marker for overproduction of inflammatory cytokines which promote nephritis, rather than the cause of renal disease in pristane-induced lupus. We propose to examine the temporal relationship between the production of autoantibodies and the development of nephritis in pristanetreated mice. Outcome of this study will answer whether anti-DNA/chromatin antibodies are obligatory for the development of nephritis or whether other factors are involved in development of renal disease. In an effort to determine if dysregulated cytokine homeostasis is sufficient to induce the production of autoantibodies and nephritis we plan to induce their constitutive expression by bone marrow derived cells. The proposed experiments will involve the transduction of hematopoietic stem cells with retroviral vectors encoding IFNg, IL-6 or both for later injection into mice. We predict that with this approach we will be able to induce autoantibody production and nephritis. Finally we aim to define the roles of ITAM vs ITIM containing Fc receptors for the development of nepliritis.We will initially study of the effect of FcgRI/III and FcgRII deficiency on pristane-induced lupus. Subsequently anti-DNA/chromatin antibody production and nephritis after pristane-treatment in FcgRI/III deficient mice over expressing IFNg or IL-6 and FcgRII deficient mice also deficient in IFNg or IL-6 will be studied. The out come of these experiments will determine if Fc receptor mediation is obligatory for the development of nephritis or whether a direct effect of cytokines alone is sufficient for the induction of renal disease. Based on our preliminary data we expect that Fc receptor signaling is the critical varialble for the induction of renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOGENESIS ERYTHEMATOSUS
OF
MURINE
SYSTEMIC
LUPUS
Principal Investigator & Institution: Kono, Dwight H. Associate Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, CA 920371000 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's abstract): Genetic susceptibility is the major predisposing factor thus far identified for spontaneous systemic lupus erythematosus (SLE) in both humans and animal models of the disease. Previously, the investigator identified in an (NZB x NZW)F2 intercross 8 loci designated Lbw1-Lbw8 on chromosomes 17, 4, 5, 6, 7, 18, 1, and 11, respectively, that exhibited evidence of linkage to one or more of four major SLE disease traits. Five of these loci have been confirmed in other crosses. The investigator has generated congenic lines for Lbw2, a locus on chromosomes 4 required for hemolytic anemia, and Lbw5, a locus on chromosome 7. Lbw5 is an autoimmune accelerator that increases the production of IgG autoantibodies and promotes hemolytic anemia, glomerulonephritis and early mortality in NZB mice. In this application the investigator proposes to: 1) define the genetics of immunoglobulin and autoantibody responses and the relationship of autoantibody specificity to other traits. This will be done by linkage analysis using an expanded set of BWF2 mice; 2) generate congenic lines for Lbw1, 2, 4, 5 and 7 to examine the effects of susceptibility and resistance alleles at these loci on clinical and immunologic manifestations; and 3) undertake positional cloning of Lbw2 and Lbw5. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOGENIC ROLE OF THE COMPLEMENT SYSTEM IN MURINE LUPUS Principal Investigator & Institution: Quigg, Richard J. Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2003 Summary: (Verbatim from Investigator's Abstract): Activation of the complement system by immune complexes (IC) leads to an inflammatory response. This occurs through the direct actions of complement proteins as well as indirectly via the stimulation of other mediator\systems. Furthermore, complement is necessary for an optimal humoral immune response to naive antigens and effective disposal of circulating ICs. The studies in this application will examine the role of the complement system in the prototypical IC disease, systemic lupus erythematosus (SLE). Here, the NZBNV F, murine model of SLE will be studied. These animals have pathological features similar to those of human SLE, including the development of a wide spectrum of auto-antibodies and diffuse proliferative glomerulonephritis that ultimately is fatal. The roles of complement will be dissected through its inhibition. Because C3 and C5 play pivotal roles in complement actions, the effects of inhibiting each will be compared in these studies. Inhibition of C3 will be achieved with the murine protein Crry (Complement receptor related protein y). Two different strategies of Crry administration will be used: 1) recombinant Crry containing a non-complement activating IgG1 "tail" (Crry-Ig) will be given chronically to animals; and, 2) transgenic mice constitutively producing endogenous soluble Crry will be studied (Crry-tg). C5 will be inhibited with an anti-mouse C5 monoclonal antibody that blocks the cleavage and activation of C5. As a parallel approach, the role of C3 in experimental SLE will also be determined by using mice made deficient in C3 through gene targeting (C3 -/- mice). Such studies will determine the effects of absolute C3 deficiency in experimental SLE. These studies will carefully evaluate how the complement system is involved in the pathogenesis of experimental SLE. The following variables will be measured: 1 ) clinical outcomes, including mortality and renal functional changes; 2) pathological alterations in kidney, including the progressive fibrogenesis occurring in glomeruli and the tubulointerstitium; 3) proinflammatory cytokines that are up regulated in these models; 4) amount and antigen specificity's of circulating and glomerular bound auto-antibodies; and, 5) the relative state of autoimmune activation of B lymphocytes. Dissecting the proand anti-inflammatory actions of the complement system in experimental SLE will provide important insights into the mechanisms of disease in human SLE, as well as in other IC diseases and may lead to viable therapeutic approaches that can be applied in practice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHASE I/II TRIAL ON THE USE OF CD20 ANTIBODY FOR THE TREATEMENT OF SLE Principal Investigator & Institution: Albert, Daniel A.; University of Pennsylvania 3451 Walnut Street Philadelphia, PA 19104 Timing: Fiscal Year 2001 Summary: Systemic lupus erythematosis is a multi-system autoimmune disease characterized by numerous autoantibodies. These autoantibodies may be responsible for most, and possibly all, of the disease manifestations. While numerous defects and abnormalities of the immune system both, innate and acquired, and endogenous and exogenous, have been described the final common denominator is aberrant antibody
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production by B lymphocytes. There are compelling arguments to support interventions aimed at reducing B lymphocyte function and/or number. Observations that support this concept are that cyclophosphamide is a is a B cell predominant chemotherapeutic agent that is highly effective in SLE, that intravenous immunoglobulin is effective therapeutically for SLE and down regulates B lymphocyte activity, that both HIV disease and anti- CD4 reduce lupus activity, and that when patients with SLE develop common variable immunodeficiency their SLE is improved. A therapeutic approach that selectively diminished B lymphocyte function or number might be a useful intervention to treat patients with SLE. Because immunoglobulin deficiency is easily reversed by pooled immunoglobulin which is not toxic (and might be somewhat therapeutic) targeted B cell therapy might be moth effective and well tolerated. Current efforts in this same direction using antibodies to the CD40 ligand are underway in a multi-center trial sponsored by Biogen and a second trial at University of San Francisco sponsored by IDEC. The CD40/GP 39 is a co-stimulatory interaction necessary for an immune response. Bon contrast, the anti-CD20 antibody is directed at a pan B cell marker and a directly inhibitory to B cells in part by antibody dependent cellular cytotoxicity. In both in vitro and in vivo studies the anti-CD20 is more effective than CD40 antibody in B cell lymphoma and should be a more effective inhibitor of B cell function. We plan an open label phase 2 trial of rituximab a chimeric anti-CD20 antibody (IDEC-C2B8) in the treatment of severe but not life threatening systemic lupus erythematosis. Patents will have failed conservative management and be candidates for cytotoxic and chemotherapeutic intervention. We will monitor disease activity by convention indices (SLEDAI and SLAM), immunologic markers of disease activity such as complement components and acute phase reactants, hematological parameters and renal function. These outcome measures will permit us to make an initial assessment of the safety and efficacy of this agent for the treatment of systemic lupus erythematosis. With these finding we will be able to plan a randomized double blind placebo controlled trial of anti- CD20 therapy for SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT STUDY--NZW DERIVED RESISTANCE TO MARINE LUPUS Principal Investigator & Institution: Ferguson, Polly J.; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-AUG-2006 Summary: Systematic Lupus Erythematosus (SLE) is a phenotypically diverse, multisystem autoimmune disorder that is caused by ill-defined interaction(s) between environmental and genetic factors. Genome wide linkage analysis of SLE multiplex families suggests there is significant racial and genetic heterogeneity, further complicating the genetic dissection of this disorder. Fortunately, there are phenotypically similar mouse models of lupus; including genetically engineered and spontaneous models. Most of the investigative work in this field has focused on identifying disease susceptibility loci; however, there are experimental data that data that suggest disease resistance genes are also important. The non-autoimmune New Zealand White (NZW) mouse does not develop lupus despite harboring the best characterized lupus susceptibility intervals and a disease permissive major histocompatibility locus [H-2z/z] suggesting that the NZW genome contains allelic polymorphisms that negatively regulate the phenotypic expression of lupus susceptibility gene(s). We hypothesize that experimental crosses between NZW and C57BL/6.FcgammaRIIB-deficient mice will allow the identification of NZW-derived intervals that attenuate the lupus phenotype(s) in this genetically engineered murine
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model of lupus. We will 1) map the quantitative trait loci (QTL) that modulate the FcgammaRIIB-/- lupus phenotype and 2) construct chromosome substitution strains (CSS) in order to dissect the genetic contribution of these individual QTL. Identification of QTL that modulate that lupus phenotype and the subsequent development of QTL containing CSS will lay the foundation for the future functional assessment of the lupusattenuating QTL and for candidate gene analysis. Understanding the genetic basis of disease resistance could facilitate the development of novel therapeutic approaches for treatment this devastating disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT--INTERLEUKIN 15 IN HUMORAL AUTOIMMUNITY Principal Investigator & Institution: Peng, Stanford L.; Washington University Lindell and Skinker Blvd St. Louis, MO 63130 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: The pleiotropic cytokine interleukin (IL)-15 has been heavily implicated in the pathogenesis of autoimmune diseases like lupus and rheumatoid arthritis because it is found at significantly elevated levels in afflicted patients, and because it is known to play critical roles in the proliferation and homing of lymphocytes. Thus, IL-15 is a potential pathogenic and therapeutic target in the rheumatic diseases; however, definitive experimental evidence remains lacking. We propose in this pilot and feasibility study to explore the mechanisms by which interleukin-15 might participate in the pathogenesis of systemic humoral autoimmunity using mutant animal models. Specifically, we will: 1. Determine the role of interleukin-15 in murine lupus, and 2. Investigate the role of interleukin-15 in the regulation of autoreactive B cell proliferation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PKR/ DIFFERENTIAL TRANSLATIONAL CONTROL IN LUPUS T CELLS Principal Investigator & Institution: Beretta, Laura; Associate Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-JUL-2006 Summary: Despite numerous advances in systemic lupus erythematosis (SLE), the molecular pathogenesis of this disease remains poorly understood. This proposal takes advantage of recent findings we have uncovered that suggest defective regulation of translation initiation in SLE. It was previously known that T cells from patients with active SLE are refractory to mitogenic stimuli. An important T cell response to mitogenic stimuli is an increased rate of protein synthesis, regulated at translation initiation. It was previously known that T dells from patients with active SLE are refractory to mitogenic stimuli. An important T cell response to mitogenic stimuli is an increased rate of protein synthesis, regulated at translation control. We investigated the effect of activating signals on translation initiation factor activates, in T cells from SLE patients. Activation by mitogens resulting in a strong increase in protein synthesis in control T cells but not in T cells from SLE patients. This lack of response in SLE T cells was further associated with over-expression of the pr4oytein kinase PKR and with increased phosphorylation of its substrate, the initiation factor eIF2alpha. Interestingly, up-regulation of PKR impairs cell functions that are relevant to lupus, including: cell proliferation, Fasdependent apoptosis, cytokine gene expression and signaling and release of Ca2+ from intracellular stores. Therefore we propose to test in this application the hypothesis that high expression of PKR and subsequent eIF2alpha phosphorylation contribute to the
Studies 91
impaired responses to mitogens in T cells from SLE patients. The specific aims are: (i) to determine the role of PKR in lupus pathogenesis. We will produce PKR-/- lupus-prone mice by backcrossing PKR knockout mice with MRL-lpr breeders. We will analyze in these mice different parameters of relevance to this lupus-like disease including serum immunoglobulin production, anti-nuclear auto-antibody response, end-organ disease and mortality. (ii) to identify specific mRNAs whose translation is highly dependent on PKR and eIOOF2alpha phosphorylation in T cells, and that may be affected in SLE. We will analyze gene products in TG cells from control mice and from transgenic mice with either a dominant negative mutant of eIF2alpha or with a targeted disruption of the PKR gene. Gene products will be identified using two-dimensional gel electrophoresis and mass spectrometry. (iii) PKR regulates cytokine signaling mediated by the transcription factor IRF-1 and we reported that IRF-1 trans-activates PKR expression. We will investigate the function of IRF-1 in lupus T cells. It is anticipated that these studiers will provide novel and important insights into mechanisms contributing to SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POST TRANSLATIONAL MODIFICATIONS AND AUTOIMMUNITY Principal Investigator & Institution: Mamula, Mark J. Senior Scientist; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant): It is the principle purpose of the immune system to protect the host from infectious pathogenic microorganisms. With that purpose in mind, lymphocytes have been programmed to differentiate self tissue antigens from foreign antigen. However, the appearance of autoimmune diseases and the presence of autoreactive lymphocytes in the normal population illustrates that the regulation of immunity is far from perfect. Systemic autoimmune diseases are the product of a complex interaction of lymphocytes, soluble macromolecules, and self tissues leading to the pathology of disease. Autoimmune responses often target multiple determinants within an autoantigen. For example, in systemic lupus erythematosus (SLE), autoantibodies are directed at a number of determinants on small nuclear ribonucleoproteins (snRNPs) and on nucleosomes. The self or foreign proteins involved in the spontaneous initiation of these autoimmune responses is not known. We have recently identified the ability of a novel post-translational protein modification, termed isoaspartyl, to confer autoimmunity to otherwise immunologically inert self peptides. For example, the immunization with isoaspartyl forms of snRNPs can provoke autoantibody responses typical of human SLE. Isoaspartyl peptide modifications arise frequently in aged and stressed cells. This application will examine the presence of isoaspartyl forms of lupus autoantigens in resting, aged, and activated lymphocyte populations and determine their ability to circumvent immune tolerance. Second, we will examine the immunologic abnormalities, lymphokine responses and intracellular signalling, in murine models unable to repair isoaspartyl modifications (PIMT knockout mice). Finally, we will study the progression of spontaneous lupus autoimmunity and pathology in MRL Lpr/lpr-PIMT-/- mice, a murine model of human SLE. This application will define the biological and immunological implications of posttranslational protein modifications. Overall, our studies will address mechanisms important in the induction and perpetuation of autoimmune disease. A more thorough understanding of the earliest events in the genesis of autoimmunity may help identify important elements to exploit for the immunologic intervention of these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POSTTRANSLATIONAL MODIFICATIONS AND AUTOIMMUNITY Principal Investigator & Institution: Doyle, Hester A. Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: The immune system has developed a number of mechanisms for recognizing foreign antigen while ignoring self-antigens. However, the presence of autoimmune diseases demonstrates these mechanisms can be bypassed. Our laboratory has demonstrated that the posttranslational modification of aspartic acid to isoaspartic acid in self-peptides induces immunogenicity to otherwise immunologically ignored peptides. Isoaspartyl residues occur spontaneously at physiological conditions and increase in aged or stressed cells. The proposed studies will examine how isoaspartyl containing self-peptides/proteins break tolerance and contribute to autoimmunity. This will be achieved by 1) examining T and B cell responses to isoaspartyl and normal forms of self-antigens, 2) determining the effect of isoaspartyl accumulation on immune function in mice deficient in the isoaspartyl repair enzyme PCMT, and 3) examining the spontaneous development of autoimmunity and pathology in PCMT -I- mice alone and backcrossed to a murine model of systemic lupus erythematosus (SLE). Results of these studies will be helpful in developing immunotherapies for the modulation of autoimmunity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREDICTION OF LUPUS OUTCOME BY GENE EXPRESSION PATTERNS Principal Investigator & Institution: Winchester, Robert J. Professor; Pediatrics; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Support is sought for performing mechanistic studies to define the gene expression profiles of glomeruli isolated from biopsy sections of lupus glomerulonephritis with the overall goals of determining whether the glomerular gene expression phenotype will predict outcome and efficacy in an ongoing parent trial. The parent trial compares administration of CellCept versus IV Cytoxan for initiating control of biopsy-proven lupus nephritis. We have demonstrated the feasibility of studying gene expression profiles by microarray analysis in glomeruli isolated from frozen biopsy sections by laser microdissection t6 characterize the molecular pathologic mechanisms leading to lupus nephritis. This work revealed considerable heterogeneity in gene expression patterns in samples classified as proliferative glomerulonephritis, suggesting the feasibility of lupus renal biopsy subclassification by gene expression criteria. The expressed genes formed 8 main clusters and the presence or absence of genes comprising these clusters in a given sample divided the biopsies into 3 distinct types. The hypothesis underlying the proposed studies is that differences in molecular pathologic mechanisms revealed by the various transcriptional phenotypes will predict the heterogeneous natural history and therapeutic outcome of lupus. The first aim of the proposed mechanistic studies is to cluster glomerular gene expression patterns in diagnostic renal biopsies performed in the current trial and use them to extend understanding of pathways involved in the molecular pathogenesis of lupus glomerulitis. Parallel quantitative PCR for selected genes found through the microarray assessment will be performed to validate the patterns found and determine if their differential expression can be used as a surrogate. The second aim will correlate the clusters and pathways with conventional pathologic
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features to identify the molecular basis of the pathologic findings. The third aim will determine whether particular outcomes of the trial could be predicted by the gene expression phenotype of the initial renal biopsy. In particular we will address, first, whether one gene expression type, characterized by apoptosis, TNF signaling and fibrosis, is highly correlated with poor outcome and thus predict the subset of nonresponders to Cytoxan or CellCept. Second, whether CellCept will prove to be efficacious in a different gene expression subset, suggesting it could be used in these cases as a less toxic alternative to Cytoxan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRESERVING OVARIAN FUNCTION IN LUPUS NEPHRITIS Principal Investigator & Institution: Dooley, Mary A. Professor; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 01-DEC-2000; Project End 30-NOV-2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROGRAM PROJECT IN THE GENETICS OF SLE Principal Investigator & Institution: Kimberly, Robert P. Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2002; Project Start 24-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Epidemiologic studies strongly support a genetic basis for susceptibility to human SLE, and genetically-defined murine models of systemic lupus indicate that lupus is a complex, polygenic disease with a threshold liability for inheritance. These studies in "lupus-like" mice suggest that different genes may control different aspects of the autoimmune phenotype. Most importantly, these studies, coupled with the rapid advances in knowledge available through the human genome project, underscore the feasibility of using the tools of modem genetics in defining human disease susceptibility and severity. The approach to the genetics of human SLE requires a multidisciplinary, team effort. Within this Program Project, we have assembled a unique and exceptionally strong multidisciplinary team, which leverages both fundamental and clinical investigations in SLE at the host institution and at the partner institutions. Our team expertise includes mastery of the theory and techniques of modem genetic mapping (linkage and association), full appreciation of the SLE clinical phenotypes and the proven ability to recruit and maintain cohorts of SLE patients (multiplex families, simplex families, case-control and longitudinal cohorts). Uniting this expertise is a broad appreciation for the pathophysiological processes in SLE in order to facilitate the selection of candidate genes and to translate findings into meaningful, mechanism-based clinical intervention. Through our team effort, we have an unprecedented power to accelerate the pace of discovery, to replicate and narrow regions of linkage, to pursue the structure and biology of candidate genes, and to test the relevance of these discoveries to clinical phenotype in a very large, meticulously studied cohort of SLE patients. Our efforts will advance our understanding of SLE and leverage both the application of current therapy and the development of new, mechanism-based therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEIN KINASE A-1 DEFICIENCY IN LUPUS PATHOGENESIS Principal Investigator & Institution: Brown, Doris R. Internal Medicine; Wake Forest University Health Sciences Winston-Salem, NC 27157 Timing: Fiscal Year 2001; Project Start 01-AUG-2001 Summary: Systemic Lupus Erythematosus (SLA) Is an autoimmune disorder that predominantly afflicts females in the child-bearing years. The cause(s) of the disorder remain unknown; however, recent progress in understanding the role of T cell dysfunctions in SLE patients has lead to progress in unravelling the molecular pathogenesis of the disease. A generalized failure of the T cell to perform its functions has been characterized in SLE. This impairment in the T cell function contributes to the destructive autoimmune pathogenesis observed in SLE patients. This proposal will investigate one pathway that may contribute to impaired T cell function. We have defined the first disorder of a protein kinase in SLE T cells, characterized by a deficient type I isozyme of protein kinase A (PKA-1). Our working hypothesis is that the RI Betasubunit protein of PKA-I is deficient due to abnormal synthesis and/or stability of the protein. Our goal is to identify the step at which RI-Beta protein production is altered in SLE T cells. The identification of the cause of RI Beta- subunit deficiency may provide the rationale in the future to apply new therapies in SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROXIMAL AUTOIMMUNITY
DETERMINANTS
OF
NEPHRITOGENIC
Principal Investigator & Institution: Foster, Mary H. Associate Professor; Medicine; Duke University Durham, NC 27706 Timing: Fiscal Year 2001; Project Start 01-JAN-1995; Project End 31-DEC-2002 Summary: (Adapted from Investigator's Abstract): Self antigen is the target of most nephritogenic immune responses, yet little is known abut the proximal events that generate, regulate, and induce expression of autoreactive lymphocytes. Effective therapy for severe autoimmune disease thus remains limited to nonspecific and toxic immunosuppression. The goal of the proposed studies is to gain a better understanding of the immunologic mechanisms that normally regulate nephritogenic humoral autoimmunity, as a basis for developing more specific interventions to eliminate or inactivate autoreactive cells and/or reestablish tolerance. These studies emphasize autoantibodies that target renal basement membrane (BM) antigens because BM proteins are the only confirmed renal targets in human autoimmune nephritis, BM is targeted in both systemic and organ-restricted autoimmunity, and regular of immune responses to these complex matrix antigens has been virtually ignored to date. The proposed studies will test the hypothesis that unmutated nephritogenic anti-laminin and anti-DNA B cells similar to those activated in systemic lupus are present but tolerant in the normal host; that their expression can be induced by inherited autoimmune susceptibility and/or environmental challenge; and that nephritogenic anti-alpha3(IV)NC1 collagen B cells persist as nontolerant ("ignorant") lymphocytes in the periphery of nonautoimmune hosts until activated by specific immunization in a permissive genetic background. The Ig transgenic approach is used for this purpose because it permits enrichment for the autoreactive B cell population of interest while preserving complex immunologic microenvironments in vivo. Six established Ig-tg lines that encode lupus anti-laminin (LamH) or nephritogenic and anti-DNA (238H) Ig will be used to determine the presence, phenotype, functional state and pathogenecity of autoreactive B cells in the nonautoimmune B6 and autoimmune MRL genetic
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backgrounds. Laminin epitopes recognized by autoantibodies will be determined, using spontaneous Ig recovered from nontolerant mice and Ig rescued from tolerance mice by in vitro or in vivo bcl-2 expression. Finally, B6 mice will be rendered transgenic for an anti-alpha3(IV)NC1 Mab that recognizes Goodpasture's epitope, to determine the tolerance phenotype of B cells specific for a cryptic and organ-restricted BM antigen targeted in severe human nephritis. The autoantibody transgenic model thus provides a well defined experimental system in which to study immunologic mechanisms and etiologic influences and to test novel therapeutic interventions for autoimmune renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RECEPTOR REVISION CREATES AUTOANTIBODIES IN LUPUS Principal Investigator & Institution: Monestier, Marc; Professor; Microbiology and Immunology; Temple University 406 Usb, 083-45 Philadelphia, PA 19122 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Antibodies to DNA or nucleosomes possess numerous positively charged amino acids, such as arginines, in their heavy chain CDR3. These cationic residues are critical contact points with negatively charged sites on the DNA helix in chromatin. Atypical VH-D-J H rearrangements such as D-D fusions contribute to create these arginine codons. Based on our preliminary data, we propose that secondary immunoglobulin heavy gene rearrangements in lupus-prone mice are responsible for potentially selfreactive VH-D-J H junctions. An increased predisposition to generate such atypical VH-D-J H rearrangements can be an important contributor to the development of lupus. We propose to test our hypothesis by accomplishing the following objectives. In Specific Aim 1, we will investigate whether lupus-prone MRL mice differ from control strains in their levels of RAG1 and RAG2 mRNA during B cell ontogeny. We will evaluate whether RAG expression is differentially affected in MRL B cells after engagement of the B cell receptor. We will also characterize, at the DNA level, VH-D-J H and D-J H rearrangements as well as other evidence of receptor revision in MRL and control B cells at various stages of development. In Specific Aim 2, we will directly test this model in vivo by examining the presence of secondary heavy chain rearrangements and autoimmune manifestations in hemizygous MRL Jh +/- mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATORY AND EFFECTOR T CELLS IN SLE Principal Investigator & Institution: Tung, Kenneth S. Professor; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 30-JUN-2003 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with protean clinical presentation and variable outcome; and glomerulonephritis (GN) is a serious manifestation of SLE. SLE patients and lupus prone mice exhibit abnormalities in B cell and T cell tolerance and their responsive state. They produce autoantibody (autoAb) response to multiple self antigens (Ag) and have immune complex (IQ deposits in tissues. The CD4+CD25+ regulatory T cells normally prevent organ specific autoimmune disease occurrence. Herein we investigate the role of the regulatory T cells in SLE by studying the effect of thymectomized on day 3 (d3tx) in lupus prone mice. The d3tx lupus prone NZM2328 mice exhibited earlier autoAb response, accumulated more glomerular IC, and developed accelerated acute GN. Remarkably, severe acute GN occurred in - 90% of male NZM2328 mice that are
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normally more resistant to lupus GN. These results have led to the following hypotheses. First, regulatory T cells can negatively influence development of SLE. Second, acute lupus GN is a T cellmediated autoimmune disease that targets the renal glomerulus. The CD4+CD25effector T cells participate in renal glomerular injury by targeting either renal Ag or Ag provided by the glomerular 1C. Thus, in SLE, autoreactive T cells: 1) drive an autoAb response, and 2) directly elicit acute GN. Third, acute GN is a checkpoint in lupus GN, from which the male mice regress and the female mice progress to chronic GN. Thus male NZM2328 mice may have less effective or more regulatory T cell function. The model will also permit the study on factors responsible for the progression and regression of lupus GN. We will investigate these hypotheses in Aim I of our proposal. A very different story emerged from the study on the lupus prone female SNF1 mice. Following d3tx, an accelerated autoAb response was also noted but this was associated with significant reduction in fatal GN. Analysis of their serum and glomerular autoAb isotypes revealed an autoimmune response with a strong Th2-bias. In Aim 2, we will test the hypothesis that d3tx of the SNF1 mice retains the nonpathogenic neonatal Th2 responsiveness. At the same time, they had a reduced Ag specific Th1 response that is required for pathogenic autoAb production and for lupus GN. Finally, we will seek an explanation for the different responses to d3tx between the two lupus prone mice. Accordingly, we will determine the outcome of CD4+CD25+ T cell depletion by methods other than d3tx in SNF1 mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATORY T CELLS IN SYSTEMIC LUPUS ERYTHEMATOSUS Principal Investigator & Institution: Bagavant, Harini; Pathology; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 31-JAN-2008 Summary: (provided by applicant): My graduate thesis was in the field of Reproductive Immunology specifically, the study of immune responses and ovarian function in primates immunized with egg protein antigens. My post-doctoral work was on the development of Contraceptive Vaccine in primates in Dr. Tung's laboratory, a part of the Center for Recombinant Gamete Contraceptive Vaccinogens at the University of Virginia (UVA). I had to take a break in my research for over one year due to family health problems. I returned to Dr. Tung's lab in July 2000 to complete and publish my post-doctoral work. At this time, Dr. Tung's lab was studying the loss of CD4+CD25+ regulatory T cell function induced by neonatal thymectomy between days 1-4 after birth (d3tx) as a cause of organ specific autoimmune disease. In addition, Drs. Fu, Tung and McDuffie had established a Specialized Center of Research for Systemic Lupus Erythematosus (SLE) at UVA. I got interested in the mechanisms of immunoregulation and initiated a project to study the role of regulatory T cells in SLE, which is a systemic autoimmune disease affecting multiple organs and characterized by the presence of circulating autoantibodies (Aab) to nuclear and cytoplasmic antigens. The project has given us exciting leads for future study and form the basis of the present proposal. We will use the d3tx model of CD4+CD25+ regulatory T cell depletion in murine SLE. Two mouse strains studied, SNF1 and NZM2328, spontaneously develop Aab and fatal glomerulonephritis (GN). D3tx in SNF1 mice accelerated Aab but protected from fatal GN. In contrast, d3tx exacerbated Aab and GN in NZM2328 mice compared to sham thymectomized (stx) mice. In addition, reconstitution of d3tx NZM2328 mice with CD25+T cells prevented exacerbation of SLE. These data suggest the hypothesis that CD4+CD25+ regulatory T cells influence induction of SLE in NZM2328 mice. Spontaneous SLE in NZM2328 has a gender bias, predominantly affecting females.
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However, depletion of regulatory T cells by d3tx results in comparable GN in both sexes. This leads to the second hypothesis that regulatory T cell function dictates the gender bias of GN in NZM2328 mice. I had a productive post-doctoral fellowship in the area of Reproductive Immunology, however, additional training in cellular immunology and renal pathology would be essential for my development as an independent scientist in lupus research. This award will help to overcome the lag period in my career induced by my leave of absence and return to a new field of study, and will facilitate my aim of becoming an independent scientist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPEATED DOSES OF LPJ-394 IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS Principal Investigator & Institution: Ballou, Stanley; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: This is a prospective multi-center double-blind, placebo-controlled Phase IIIII trial in which an investigational new drug, LPJ 394, will be tested for its ability to reduce the production of antibodies to double stranded DNA (anti-dsDNA) and limit flare-ups of active renal disease in patients with lupus nephritis. The subjects will receive medication for 52 weeks, after which there will be a six month period of followup to assess clinical lupus activity, anti-DNA levels and health status. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF ARGININE DEFICIENCY IN PATHOGENESIS OF LUPUS Principal Investigator & Institution: Satoh, Minoru; Medicine; University of Florida Gainesville, FL 32611 Timing: Fiscal Year 2003; Project Start 25-SEP-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Immunological characteristics of systemic lupus erythematosus (SLE) include polyclonal B-cell activation and production of specific autoantibodies. However, the autoimmune response is highly restricted to only a few antigens, indicating that there are mechanisms to specifically select target antigens. Autoantibodies to small nuclear ribonucleoproteins (snRNPs: Sm and nRNP) are frequently produced in SLE, MRL mice, and pristane-treated normal mice. In pristanetreated mice, the U1-70K, which has an unusually high arginine content (21%), appears central to the autoimmune process. Arginine is consumed by activated macrophages and arginases in inflammatory sites. In addition, L-canavanine, a non-protein amino acid homologue of L-arginine present in higher plants, may be efficiently incorporated into proteins, producing aberrant proteins that could create cryptic epitopes capable of triggering autoimmunity. In this study, we will investigate why U1 snRNPs are selectively targeted in pristane-induced lupus. We hypothesize that the arginine-rich U1-70K is aberrant in arginine-deficient pristane granulomas, generating cryptic epitopes that initiate autoimmunity. In aim 1, whether arginine is deficient in pristanetreated mice will be examined by amino acids analysis. Arginine metabolism (uptake, consumption, and reconversion) also will be evaluated. In Aim 2, U1-70K synthesized in arginine-deficient conditions and in the presence of L-canavanine in vitro will be evaluated for modifications by immunoprecipitation, amino acid analysis, and mass spectrometry. U1-70K from cells in pristane-treated mice also will be examined. In Aim 3, whether aberrant UlsnRNPs (arginine-deficient, L-canavanine containing) can trigger
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a specific autoimmune response will be investigated by immunizing mice with purified UlsnRNPs or apoptotic cells derived from these conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF NFAT PROTEINS IN CD154 GENE REGULATION AND LUPUS Principal Investigator & Institution: Cron, Randall Q.; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, PA 19104 Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 30-JUN-2004 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by pathogenic autoantibodies that are dependent on T lymphocyte interactions with autoantibody producing B- lymphocytes. This interaction is reliant on CD40-1igand (CD154), which is expressed on the surface of activated CD4 T cells and which engages its cognate cell surface receptor, CD40, on B cells. Because of its critical and pleiotropic role in the immune system, CD154 expression is normally tightly regulated. Several recent reports have described dysregulated (increased and prolonged levels) expression of CD154 in patients with SLE relative to normal controls. Similar findings have been made in lupus-prone mice, and treatment of these mice with a neutralizing anti-CD154 monoclonal antibody delays and reduces the incidence of glomerulonephritis, a hallmark of SLE. However, similar approaches in humans have not proven efficacious due to unanticipated side effects involving coagulation. The expression of CD154, like that of other T cell cytokine genes, is controlled at the level of gene transcription. We have previously characterized the CD154 transcriptional promoter and demonstrated its dependence on the nuclear factor of activated T cells (NFAT) for activation-induced expression in T cells. Others have shown that CD154 expression is markedly decreased in T cells from mice deficient in NFAT1, the most prominent NFAT family member in T cells of the peripheral immune system. Therefore, we predict that NFAT1 will be critically important for endogenous CD154 expression in peripheral CD4 T cells, and that increased expression of NFATI, or other NFAT family members, contributes to the hyper-expression of CD 154 in patients with SLE. We will test the role of NFAT1 on endogenous CD 154 expression by T cells in vivo under circumstances where NFAT1 is limiting using mice that conditionally express NFATI in T cells only. To examine the role that NFAT1 and other NFAT proteins play in the abnormal expression of CD154 in SLE, primary human CD4 T cells from SLE patients and controls will be evaluated for NFAT RNA and protein levels, as well as for functional NFAT activity using reporter gene assays. Lastly, inhibition of NFAT activity in primary lupus CD4 T cells will be attempted using a newly described NFAT-specific inhibitory peptide. Ultimately, these studies may lead to alternative approaches to inhibiting NFAT activity, and the subsequent over-expression of CD154, in SLE T cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF NITRIC OXIDE AND EICOSANOIDS IN LUPUS NEPTHRITIS Principal Investigator & Institution: Oates, James C. Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 25-APR-2001; Project End 28-FEB-2006 Summary: Lupus nephritis (LN) leads to renal failure in up to 50% of cases over 5 years despite aggressive immune suppressing therapies that are nonspecific and often
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contribute to significant morbidity and mortality. Further investigations into the pathogenesis of LN are necessary to develop targeted therapies. Elevated nitric oxide (NO), isoprostane, and thromboxane (TXA2) and reduced prostacyclin (PGI2) synthesis occur in LN. TXA2 synthase inhibitors, TXA2 receptor antagonists, and inducible NO synthase (iNOS) inhibitors abrogate murine LN, while the same TXA2 specific therapies improve renal function in human LN. No combines with superoxide to form peroxynitrite (ONOO), which can alter TXA2 and PGI2 metabolism. Thus, one mechanism by which NO may be pathogenic in LN is through the effect of ONOOinduced alternations in intra renal accessioned synthesis. To test this hypothesis, the following specific aims are proposed: 1) Correlate systemic ONOO production in humans with LN with urinary excretion of 8-is PGF2a ( an isoprostane) and the excreted renal metabolites of TXA2, PGI2 and PGE2. Alter ONOO production in murine LN using pharmacologic an genetic means and measure the renal synthesis and urinary excretion of the same eicosanoids, GFR, and nitration of renal TXA2 and PGI2 synthase. 3) Isolate glomeruli from murine models of LN and measure directly the effects of exogenous NO and ONOO donors and iNOS inhibitors on accessioned synthesis and determine if nitration of renal TXA2 and PGI2 synthase occurs. We will measure longitudinal SLE and LN disease activity (in 38 SLG and 38 LN subjects compared to 38 controls) and correlated these with serum 3NT and renal accessioned synthesis. To determine if NO and ONOO exert downstream effects on accessioned metabolism, we will measure the same parameters in 2 models of murine LN in response to iNOS inhibition (with iNOS inhibitors, vitamin E, and MRL/lpr iNOS -/- mice). Glomeruli from murine models of LN will be isolated to determine in vitro the effect of iNOS inhibitors and NO/ONOO- donors on accessioned synthesis. Determining the pathogenic mechanisms of ONOO production as it relates to accessioned synthesis in LN may lead to the use of specific iNOS inhibitors in humans with LN. If we disprove our hypothesis that ONOO induces alternations in eicosanoid synthesis in LN iNOS activity and eicosanoids synthesis may be triggered by common or parallel upstream mechanisms. Alternatively, eicosanoids could regulate NO synthesis in LN as they can in some experimental systems. In either event, future studies would address the use of selective COX-2 or TXA2 synthase inhibitors/receptor blockers, antioxidants, and/or PGI2/PGE2 agonists in conduction with iNOS inhibitors as therapies for LN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SIXTH ERYTHEMATOSUS
INT
CONFERENCE
ON
SYSTEMIC
LUPUS
Principal Investigator & Institution: Lockshin, Michael D. Professor; Hospital for Special Surgery 535 E 70Th St New York, NY 10021 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: Support is requested for travel of participating American investigators to the Sixth International Conference on Systemic Lupus Erythematosus (SLE), to be held March 26-28, 2001, in Barcelona, Spain. This conference will bring together investigators and practitioners from around the world to summarize and reflect on a vast accumulation of new data in the three years since the Fifth Conference. Topics to be highlighted in plenary sessions are: pathogenesis, accelerated atheroma, autoimmune response, antiphospholipid syndrome, autoantibodies as cause, prognosis and future research. Topics featured as 'hot topics' are: prolactin, stem cell transplantation, and nucleosomes. Regular session topics include: epidemiology, lupus in childhood and the elderly, lymphocytes, nephritis, neonatal lupus, animal models, cerebral lupus, druginduced lupus, infection, immunogenetics, malignancy, autoantibodies (clinical),
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autoantibodies (immunology), autoantibodies (pathogenic mechanisms), skin, sex hormones, pregnancy, disease activity/damage, cardiovascular disease, geographical lupus, apoptosis, treatment, cytokines, overlap syndromes, future therapies, and vasculitis. Six sessions will be devoted to free papers and three to poster presentations. Each session will be chaired by a world leader in the topic and will focus on new information in each subfield (including pathogenesis and disease measurement), how this new information influences practice, animal models (including transgenics), and current and future therapies. Women and minorities are represented among session chairs, invited speakers, and organizers. This meeting brings together international investigators who seldom otherwise meet as a group to discuss this important disease. These investigators include basic scientists, clinical scientists, and practitioners from several specialties, including neurology, nephrology, hematology, obstetrics, internal medicine and family practice. The conference provides opportunities for collaborations and reagent exchange. Funding will allow participation of young investigators in this field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLE DISEASE ACTIVITY--PREDICTORS OF MORBIDITY AND HEALTH Principal Investigator & Institution: Tucker, Brian; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: The Lupus Center at JHH is uniquely situated to address clinical research issues through prospective follow-up of a large number of SLE patients. During Dr. Petri's FIRST award, issues addressed included the risk of future thrombosis and coronary artery disease associated with antiphospholipid antibodies, routine cardiovascular risk factors, and prednisone use. The Lupus Cohort has now been refunded by the NIH. The specific aims of the RO-1, although a continuation of the FIRST award work, now include an emphasis on disease activity and disability. Ongoing disease activity exposes patients to the side effects of corticosteroids. Over onehalf of patients sustain permanent organ damage. Determination of predictors of disease activity should help to reduce unneeded corticosteroid treatment and allow institution of earlier treatment when it is needed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPECIALIZED CENTER OF RESEARCH IN SYSTEMIC LUPUS ERYTHE* Principal Investigator & Institution: Fu, Shu Man M. Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, VA 22904 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-JUN-2007 Summary: (provided by applicant): Systemic lupus Erythematosus is a prototypic autoimmune disease affecting multiple systems. This disease causes significant morbidity and mortality. The University of Virginia Specialized Center of Research in Systemic Lupus Erythematosus (UVa SCOR in SLE) was established in July 1998 with funding from the NIAMS. The Center has successfully fostered a multi-discipline approach to study the pathogenesis of this disease. The consortiums between the University of Virginia and the Mayo Clinic and the Johns Hopkins Hospital have strengthened the SCOR. Studies on a new strain of lupus- prone mice NZM2328 have led to the identification of new SLE susceptibility loci, the distinction between acute and
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chronic glomerulonephritis, and most importantly the dissociation of ANA, anti-dsDNA and anti-nucleosome antibody production from chronic glomerulonephritis. Significant information has been obtained regarding the mechanism of epitope spreading in the autoantibody diversification to SLE-related autoantigens. The identification of crossreactive T cells is a major advance in the understanding of this process. Two 3-day thymectomy models to study the role of CD25+ regulatory T cells have been developed. Models for Sjogren's syndrome/autoimmune sialoadenitis have been created. Studies of the DR and DQ transgenic mice provide evidence for the importance of the DR antigens in determining the specificities of the autoantibodies produced. Studies involving serial patient samples provide evidence for fluctuation of autoantibody titers without clear correlation with patients' clinical courses. A collaboration between the University of Virginia and the National Institute of Immunology in India has established a program to study the role of DR in the generation of anti-Sm antibody responses by exploring the ethnic and environmental differences between the India and the U.S. populations. Studies on the role of estrogen receptors in the pathogenesis of SLE show interesting preliminary data. These advances form the basis for the competitive renewal. The competitive renewal application will continue to develop the interdisciplinary approach to study the immunological, genetic and environment factors important in the pathogenesis of SLE. The SCOR renewal application has four projects and three cores. The projects are 1) HLA-D Molecules, T Cell Epitopes and Autoantibody Specificities in SLE; 2) Regulatory and Effector T Cells in SLE; 3) Genetic Control in Lupus-prone NZM2328; and 4) Estrogen Receptors in SLE and the UVa Lupus Cohort. The proposed studies are to provide experimental evidence to support the stated hypothesis that molecular mimics (environmental factors) may initiate an autoimmune response, and the diversification of the autoimmune response with inflammation leads to end-organ damage in appropriate hosts. The three cores are 1) Administrative Core, 2) Cell Sciences and Immunochemistry Core, and 3) Mouse Genetics Core. These cores will serve all the projects and will continue to facilitate interaction among investigators within the UVa SCOR in SLE. The SCOR continues to represent both inter- and intrainstitutional collaboration. It is expected that this interactive approach will continue to provide new insights into the immunological and genetic factors important in SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNDROME
SPORADIC
MECHANISM
OF
THE
ANTIPHOSPHOLIPID
Principal Investigator & Institution: Merrill, Joan T. Member and Head; St. Luke's Roosevelt Hosp Ctr (New York) 1111 Amsterdam Ave New York, NY 10025 Timing: Fiscal Year 2001; Project Start 15-MAR-1999; Project End 31-JUL-2001 Summary: (Adapted from the applicant's abstract)-The APLS is an autoimmune disease of sporadic and unpredictable thrombosis which leads to miscarriages, venous clots, strokes, and sudden death of young people. The only clinical tests available are nonspecific screening assays which detect a lupus anticoagulant or antiphospholipid autoantibodies, but do not predict which patients will develop life- threatening disease. Because of this, patients do not receive anticoagulant therapy until after a serious thrombotic event occurs. Then they are left on potentially dangerous anticoagulant regimens for life, with no assurance that they need it. There is an obvious mandate for better predictive testing and for more specific therapies aimed at the underlying coagulation disorder in this syndrome. A critical aspect of the problem that must be addressed by a disease model is the sporadic nature of the thrombotic events that occur. This application will evaluate a likely model for sporadic thrombosis, transient
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functional deficiency of the anticoagulant protein S. Functional protein S deficiency results from excessive binding by a protein S inhibitor, the C4BP, a dual regulator of the complement and coagulation systems. Functional inhibition of protein S by C4BP has been recently found in patients with APLS by many authors and is temporally related to clotting events. The applicants determined that beta2-GPI, the major target antigen for antiphospholipid autoantibodies, binds protein S and reverses inhibition of protein S by C4BP. A monoclonal anti-beta2-GPI antibody inhibits its interaction with protein S and causes functional protein S deficiency in vitro. The applicants hypothesize that a subset of pathogenic antiphospholipid autoantibodies inhibit interaction between beta2-GPI and protein S, causing intermittent thrombosis during states of high complement activity and excess C4BP, such as are found during lupus flare and pregnancy. The applicants propose to define interactions between protein S, beta2- GPI, and C4BP on a molecular level. Beta2-GPI and C4BP share homologous regions associated with the complement control protein superfamily. These are likely protein S-binding sites and will be targeted in mutagenesis experiments aimed at finding epitopes to which pathogenic antibodies bind. Peptides derived from the protein S-binding region of beta2-GPI might serve as antigens for a more specific clinical assay for pathogenic antiphospholipid autoantibodies or as a basis for a novel therapeutic agent. They will also evaluate the significance of the sex hormone-binding globulin (SHBG) region on protein S. Pregnancy is a risk factor for thrombosis in APLS, and decrease in protein S function is associated with oral contraceptive use. Therefore, possible modulation by sex-hormones of interactions between these proteins will be addressed in this application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SRC TYROSINE KINASES AND AUTOIMMUNITY. Principal Investigator & Institution: Defranco, Anthony L. Professor and Chair; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 30-SEP-1993; Project End 30-NOV-2006 Description (provided by applicant): The immune system must decide whether to mount an immune response to a particular entity or whether to ignore it. The latter outcome is referred to as immunological tolerance. A great deal has been learned about tolerance over the past decade, but our understanding is still fragmentary, despite its importance for understanding autoimmune disease, managing acceptance of organ transplants, and promoting cancer immunotherapy. We have unexpectedly found that mice deficient in the Lyn tyrosine kinase have B lymphocytes that exhibit elevated responsiveness to antigenic stimulation. In vivo, these mice make high levels of autoantibodies directed at nuclear components such as double-stranded DNA and some of them develop kidney disease. Double mutant mice defective in Lyn and another Srcfamily kinase, Fyn were found to develop a much more severe autoimmune lupus-like kidney disease, with 50% of the animals dying by 7 months of age. We hypothesize that the defect in Lyn makes B cells hyperresponsive and also defective in tolerance induction, resulting in production of antibodies directed at nuclear components released by apoptotic cells. We further hypothesize that the defect in fyn contributes to more rapid disease incidence, possibly by making the kidneys more susceptible to damage resulting from immune complex deposition. In addition, Fyn-deficiency may lead to defects in T cell tolerance. These hypotheses will be tested by three Specific Aims: 1) We shall determine the effects of Lyn and Fyn deficiencies on tolerance to double-stranded (ds) DNA using Ig- transgenic mice developed by Martin Weigert and coworkers. 2) We shall determine the role of helper T cells in IgG anti-dsDNA production by Lyn-/- mice
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and examine the effects of lyn and fyn defects on T cell tolerance, and 3) We shall define the cellular basis of defects leading to autoimmune disease in lyn-/-fyn-/- mice. This will be done by bone marrow transplantation and by adoptive transfer of mature lymphocytes. The proposed studies may lead to significant insights into the nature of the severe autoimmune disease in lyn-/-fyn-/- mice, which in turn may aid in understanding the causes of human autoimmune diseases such as systemic lupus erythematosus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDIES OF SYSTEMIC LUPUS ERYTHEMATOSUS Principal Investigator & Institution: Diamond, Betty A. Professor; Microbiology and Immunology; Yeshiva University 500 W 185Th St New York, NY 10033 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2007 Summary: Four physician-scientists will share model systems, reagents and methodologies to expand an interactive program for preclinical and clinical studies on the pathogenesis and treatment of systemic lupus erythematosis. Drs. Davidson, Diamond, Porcelli and Putterman are practicing rheumatologists with established research programs focused on aspects of the initiation of autoreactivity and the mechanisms of target organ damage in SLE. Three core facilities will provide essential support in administration, flow cytometry, and protein expression and tetramer production. Dr. Diamond has recently developed a novel approach for the identification and analysis of autoreactive B cells at the single cell level using fluorescent tagged tetramers of a peptide mimetope for DNA. She will use the methodology to determine which B cell subsets give rise to anti-DNA antibodies in patients with SLE. DR. Davidson proposes to examine the role of newly identified costimulatory molecules in the NZB/W F1 model of lupus and in the peptide antigen-induced model of lupus pioneered by Drs. Diamond and Putterman. Using novel reagents for costimulatory blockade, she will ask whether the memory of B cell compartment is critical in the progression of disease and in relapse after therapy in murine models of lupus. Dr. Porcelli is interested in CD1 restricted T cells. Based on novel data on the regulation of potentially autoreactive marginal zone B cells, he proposes to study the involvement of the CD1 system in the NZB/W F1 mouse and in the antigen-induced model of SLE mentioned above. Dr. Putterman is studying tissue damage in lupus, focusing on antiDNA antibody-mediated kidney disease. He has recently identified a glomerular antigen recognized by a significant fraction of anti-DNA antibodies; he will explore this antigenic specificity to develop a model for glomerular damage. Together these studies new information and new methodologies to address critical aspects of disease initiation and progression, and tissue damage in lupus. The strategy is to apply information obtained from murine studies to studies of the human disease; thus, the program includes several studies in mice and one study addressing the phenotypic analysis of human lupus B cells drawing on methodologies and hypotheses derived from murine studies. The goal is to develop "designer" therapies tailored to particular subsets of patients with particular patterns of disease induction and tissue injury. This effort is based on already existing interactions among the investigators and will be substantially strengthened by the resources provided by the Program Project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STUDY OF DEXAMETHASONE IN NEONATAL LUPUS CHB Principal Investigator & Institution: Buyon, Jill P. Professor; Hospital for Joint Diseases Ortho Inst Orthopaedic Institute New York, NY 10003
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Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Taken from the application): Neonatal lupus is currently considered a model of passively acquired autoimmunity whereby immune abnormalities in the mother (who may have systemic lupus erythematosus, Sjogrens syndrome, or be entirely asymptomatic) lead to the production of antibodies to the SSA/Ro-SSB/La ribonucleoproteins which cross the placenta and presumably injure the developing fetus. The most serious manifestation is cardiac injury which includes varying degrees of atrioventricular (AV) block, most often third degree, and myocarditis. The mortality approaches 20% and the majority of children require lifelong pacing. This application focuses both on the clinical approach to diagnosed congenital heart block (CHB) [interventional study] and the search for an early echocardiographic marker of injury [observational study]. In Specific Aim 1, a randomized double-blind placebo-controlled trial will examine the effect of daily oral dexamethasone (4 mg) on the outcome of CHB. The rationale rests on the hypothesis that CHB is the consequence of an inflammatory process mediated by maternal anti-Ro/La antibodies. Mothers, irrespective of disease activity but requiring less than 10 mg prednisone/day, identified before 30 weeks of gestation to be carrying a fetus with CHB, will be randomized to receive dexamethasone or placebo (50 patients per arm) for a minimum of 6 weeks. Primary outcome measures include neonatal ventricular rate and ejection fraction at birth, and presence or absence of abnormal fluid collection as assessed on the final fetal echocardiogram before delivery. Secondary outcome measures include the degree of block at birth, gestational age, birth weight, and cardiothoracic ratio. In Specific Aim 2, we will attempt to identify the earliest noninvasive echocardiographic marker of AV nodal dysfunction and/or myocardial injury. At present it is not known whether injury to the AV node progresses through stages with the final outcome being fibrosis of the node and irreversible third degree block. It has been proposed that global inflammation of the working myocardium and surrounding pericardium may precede or accompany AV nodal injury. One hundred pregnant women considered at high risk for having a child with CHB, as defined by presence of Ro/La antibodies documented prior to pregnancy (regardless of whether or not they have had a previous child with neonatal lupus), will be followed by weekly echocardiograms from 16 weeks of gestation, with special attention to prolongation of the mechanical PR interval and/or development of myocardial dysfunction. Mothers whose fetuses develop 1st, 2nd or 3rd degree block will then be randomized to receive either dexamethasone or placebo as part of Specific Aim 1. The importance of this second aim is twofold: first, it will identify whether the subclinical incidence of tissue injury exceeds overt injury manifest as advanced AV dissociation; and second, it will provide the best chance for reversibility of block given identification of early lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: T PNEUMONITIS
CELL
ADHESION
MOLECULES
IN
MURINE
LUPUS
Principal Investigator & Institution: Curtis, Jeffrey L. Professor of Internal Medicine; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 30-NOV-2002 Summary: Pulmonary involvement in systemic lupus erythematosus (SLE) is common, often incapacitating, and occasionally lethal. Current therapies are less effective for pulmonary involvement than for other organ systems. To define the molecular pathogenesis of SLE, we have developed a murine model system that depends on
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adoptive transfer of syngeneic activated CD4+ T cells treated with DNA methyltransferase (DNA MTase) inhibitors such as procainamide (Pca). Normal AKR mice receiving cells of the cloned T cell line D10 that have been treated with Pca (D10Pca) develop high-titer anti-DNA autoantibodies, nephritis, liver disease resembling biliary cirrhosis, and lymphoid interstitial pneumonitis (LIP). Splenectomy abrogates disease activity in all organs except the lungs, indicating that pathology in this organ does not depend of autoantibody production. Treatment with DNA MTase inhibitors increases expression of the Beta2 integrin LFA-1 (CD11a/CD18). T cells transfected with CD18 are also autoreactive and induce lupus on transfer to syngeneic mice. Lymphocyte DNA hypo-methylation and LFA-1 over-expression is also seen in patients with active lupus. These findings imply that T cell overexpression of LFA-1 is sufficient to initiate SLE, and that the T cell-dependent lung lesion may be the earliest stage in the process. This proposal will examine the molecular mechanisms involved in lung pathology in this model system, utilizing a variety of techniques and lessons learned from the study of other models of lung lymphocyte trafficking. Central Hypothesis: Increased LFA-1 expression by autoreactive T cells mediates adhesion both to lung endothelial cells and to lung antigen-presenting cells (APCs), especially macrophages (Mphis) (resulting in apoptosis and release of autoantigens). These interactions initiate recruitment of other activated T cells to the lung via VLA-4/VCAM and selectin-dependent interactions, inducing LIP. Specific Aim 1: To verify the lung localization of D10Pca is required to induce drug-induced murine LIP. Specific Aim 2: To determine the adhesive interactions mediating lung localization of D10Pca and other lung lymphocytes during development of LIP. Specific Aim 3: To determine whether inhibiting pulmonary retention of D10Pca via monoclonal antibody (mAb) treatment prevents development of LIP. Our long-term goal is to develop effective therapies to treat established SLE based on anti-adhesive strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: T CELL COST IMMULATION ON MURINE LUPUS Principal Investigator & Institution: Daikh, David I. Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 31-AUG-2003 Summary: Systemic Lupus Erythematosis is a systemic autoimmune disease of unknown cause characterized by the production of antibodies directed against a variety of self antigens. A spontaneous form of lupus which closely parallels the human disease also occurs in the lupus-prone B/W mouse. Production of autoantibodies in humans and the B/W mouse is dependent on activated CD4+ helper T cells. Activation of these T-cells requires interactions between the T-cell antigen receptor and antigen presented by an antigen-presenting cell, as well as a second signal which can be provided by interactions between B7 molecules on antigen- presenting cells and the CD28 molecule on the T-cell. Blockade of the first signal by antibodies against the CD4 molecule is effective in preventing or reversing lupus in the B/W mouse, an observation which in part led to therapeutic trials with anti-CD4 antibodies in humans with autoimmune disease. Blockade of the second activation signal by a soluble molecule called aLA4Ig has recently been shown to dramatically slow the progression of lupus in B/W mice as well as treat established disease. The mechanism of this effect, however, is unknown. T cell costimulation can also be provided by interactions between CD4O and its cognate ligand gp39, but the role of these molecules in autoimmunity is also unknown. The objective of the current proposal is to further define the mechanism by which interruption of T-cell costimulation can block the development of autoimmunity. This
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objective encompasses five specific aims: Specific Aim 1. To determine the relative contributions of B7-1 and B7-2 to the development of autoimmunity in lupus-prone NZB/NZW (B/W) mice. Specific Aim 2. To determine if blockade of CD28 and/or CTLA4 early in life can induce tolerance to autoantigens. Specific Aim 3. To determine the effects of costimulation blockade on T cell cytokine production in lupus-prone mice Specific Aim 4. To determine the role of Th1 and Th2 cells in the development and maintenance of murine lupus. Specific Aim 5. To determine whether interruption of multiple costimulation signals can have a synergistic effect on murine lupus. These studies will not only define the critical costimulation signal(s) necessary for the development of murine lupus, but should point to new, more specific therapeutic approaches in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: T CELLS AND THE INDUCTION OF LUPUS Principal Investigator & Institution: Richardson, Bruce C. Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-1993; Project End 30-JUN-2002 Summary: (Adapted from the applicant's abstract)-Decreased T cell DNA methyltransferase (MTase) activity has been causally linked to human lupus. The principal investigator's group has reported that inhibiting DNA MTase in dividing T cells results in DNA hypomethylation, LFA-1 overexpression, and autoreactivity, and that adoptive transfer of the autoreactive cells is sufficient to cause a lupus-like disease. They have also shown that some agent which induce lupus, including procainamide, hydralazine, and UV light, inhibit T cell DNA methylation, increase LFA-1 expression, and induce autoreactivity, and they have used the adoptive transfer model to demonstrate a mechanism by which these agents can trigger a lupus-like disease. They and others have shown that T cells from patients with active lupus have diminished levels of DNA MTase, hypomethylated DNA, and overexpress LFA-1 on an autoreactive T cell subset, indicating that a similar mechanism could contribute to idiopathic SLE Together, these results suggest that abnormally decreased T cell DNA MTase enzyme activity may directly contribute to the development of drug- induced and idiopathic lupus by modifying T cell gene expression. The mechanisms regulating human DNA MTase are unknown. This group has established that levels of DNA MTase normally increase following T cell stimulation. They have also obtained evidence that human DNA MTase levels may be regulated through the ras-MAPK signaling pathway. In other studies the principal investigator found that the mitogen-stimulated increase in DNA MTase is impaired in T cells from patients with active lupus, and the Ha-ras mRNA levels and ras-MAPK signaling are diminished in these T cells, suggesting a mechanism for the decreased DNA MTas response. Finally, the principal investigator has evidence for multiple isoforms of human DNA MTase, the function and expression of which are unknown. The principal investigator hypothesizes that decreases in the levels of DNA MTase, due to decreased Ha-ras expression, may contribute to the development of lupus. The principal investigator also hypothesizes that the different isoform of DNA MTase serve distinct roles within the cell. The specific aims are to: 1 Determine the role of the ras-MAPK signaling pathway in the regulation and function of human T cell DNA MTase; 2) determine the pathologic significance of decreased Ha-ras pathway signaling using a novel model of drug-induced lupus; 3) determine the significance of the decreased Ha-ras levels observed in T cells from patients with active lupus, and 4) characterize expression of DNA MTase isoforms. The principal
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investigator anticipates that these studies will clarify mechanisms contributing to the development of human lupus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: T LYMPHOCYTE DYSFUNCTION IN LUPUS ERYTHEMATOSUS Principal Investigator & Institution: Kammer, Gary M. Professor; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, NC 27157 Timing: Fiscal Year 2001; Project Start 01-SEP-1994; Project End 31-AUG-2002 Summary: (Adapted from investigator's Abstract): An important defect in SLE is T cell dysfunction, manifested as reduced proliferation to mitogens or antigens, reduced release of IL-2 and impaired generation of suppressor T cells. In this proposal, the Principal Investigator builds on his carefully established observation that the activity of the adenyl cyclase/cyclic AMP/protein kinase A isozyme phosphotransferase signal transduction pathway (specifically of the R1 subunit of PKA-1), is defective in 88% of people with SLE. PKA is the only cytosolic pathway for cAMP-mediated phosphorylation of multiple membrane and cytosolic proteins. The Principal Investigator has isolated the abnormality to the R1 subunit of the holoenzyme, and has shown that quantities of R1 are normal in SLE patients, but activity is reduced. His hypotheses are 1) that the defect is due to point mutations in R1a and/or R1b isoforms comprising the regulatory subunits of PKA-1, and 2) that these defects are inherited. A large body of previous work and preliminary data are presented. Specific Aims are: 1. To study a cohort of unrelated people with SLE to estimate the prevalence of deficient PKA-1 activity in DLE, SCLE and SLE, determine whether activity of enzyme relates to activity of disease, whether it differs in different races and sexes, and if it is a heritable trait in the families of these patients; 2. To identify mutations of the R1a or R1b subunit by SSCP and sequencing of cDNA from cloned PCR products and genomic DNA. Preliminary data show 2 examples of such mutations - both are T to A with F replacing I - one in R1a and the other in R1b, both located in regions likely to impair folding of the A and B subunits which permits full cAMP binding. Screening for mutations will use gel shift in SSCP or competitive PCR; bands of interest will be sequenced. 3. To prepare mutant and wild-type recombinant R1a and/or R1b subunit proteins from lupus subjects to quantify isozyme kinetics and phosphotransferase activities to determine if and how the mutations affect function. 4. To examine transcriptional and posttranscriptional regulation of R1a and R1b subunit mRNA in T cells from active and inactive SLE vs controls by quantifying the mRNA content, cytoplasmic mRNA turnover and amounts of each isoform protein. Transcription will be inhibited at various stages by actinomycin D and dichloro-b-D-ribouranosylbenzimidazole). Amounts will be measured by immunoblotting of 35S-labeled material. 5. To screen lupus families to determine whether the mutation is passed through lupus families and is associated with a PKA-1 isozyme deficiency. The Principal Investigator will study 14 families with 3 generations available - beginning with a lupus proband with a mutation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TARGETED COMPLEMENT INHIBITORS Principal Investigator & Institution: Tomlinson, Stephen; Associate Professor; Microbiology and Immunology; Medical University of South Carolina 171 Ashley Ave Charleston, SC 29425 Timing: Fiscal Year 2001; Project Start 01-MAY-1994; Project End 31-AUG-2004
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Summary: (Adapted from the Investigator's abstract): The broad long term objective of the proposed research is to develop novel complement inhibitory proteins for the effective and safe treatment of autoimmune and inflammatory disease. The specific aims of this application are to: 1. Prepare and characterize complement inhibitory proteins that can be targeted to specific tissues or sites of disease. Different classes of complement inhibitor will be fused to a targeting component consisting of either an antibody variable region or a receptor ligand. 2. Evaluate the therapeutic potential of targeted complement inhibitors in a murine model of spontaneous systemic lupus erythematosus (SLE). 3. Determine the effect of systemic complement inhibition on host ability to control an infection during chronic disease. Soluble CD59 or DAF functional units will be fused to either antibody fragments containing a variable region specific for a cell surface molecule, or to a soluble ligand recognizing selectins. Selectins are cell adhesion molecules that are expressed on inflamed endothelium and are involved in leukocyte recruitment. Various construct designs will be evaluated in vitro for selective targeting to a cell surface, and for their functional effectiveness at inhibiting complement and complement-dependent inflammatory processes. Complement inhibitory proteins based on antibody fusions that are effective in vitro will be tested in vivo in a murine model. A characterized murine anti-DNA antibody that has been shown to target to the kidney will be used for the preparation of IgG-complement inhibitor fusion proteins. Anti-DNA antibodies of the kind that will be used are relatively specific for lupus and have a pathogenic role in disease. Studies will determine the relative effects of targeted vs. untargeted (systemic) complement inhibitors, as well as the effect of selectively blocking the generation of different complement activation products. In addition to therapeutic evaluation, the proposed studies will allow testing of certain hypotheses relating to complement-associated disease mechanisms and the clinical use of complement inhibitors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE GENETIC EPIDEMIOLOGY OF RA AND SLE Principal Investigator & Institution: Criswell, Lindsey A. Associate Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 27-SEP-2001; Project End 31-MAY-2006 Summary: (Taken from the applicant's abstract): Dr. Lindsey Ann Criswell has demonstrated a strong commitment to patient-oriented research since the beginning of her rheumatology fellowship training at the University of California, San Francisco (UCSF). Dr. Criswell's track record in peer-reviewed publications and her ability to successfully compete for NIH and other sources of research funding provide compelling evidence of her ability to conduct high quality patient-oriented research. Furthermore, Dr. Criswell has successfully mentored a large number of junior clinical investigators who are now establishing their own independent patient-oriented research programs. During the past six years, Dr. Criswell's research program has focused on the genetic epidemiology of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This work has led to several important findings, including the association of tumor necrosis factor polymorphism with RA severity through an interaction with the HLADRB 1 shared epitope. Due to the rapid pace of advances in analytic methods for genetically complex diseases such as RA and SLE, Dr. Criswell must continue to devote a substantial amount of time and effort to mastering these rapidly evolving methods. The K24 award offers a unique opportunity to provide support for this essential ongoing training. Dr. Criswell's immediate research goals are to successfully complete the research that is now funded and underway within her research unit. This application
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describes 3 projects that utilize state of the art methods to identify genetic and nongenetic risk factors for these complex diseases. The expertise of the study investigators in the areas of rheumatology, genetics and statistics, in conjunction with the progress of these studies to date, ensures a high likelihood of success for this work. The research environment at UCSF provides an outstanding environment in which Dr. Criswell can continue to develop as a leader in patient-oriented clinical research and as a mentor to junior clinical investigators. As a result of Dr. Criswell's role as the Associate Director of the UCSF General Clinical Research Center (GCRC), she is ideally positioned to make a major impact at UCSF as a mentor for young clinical investigators. Dr. Criswell has precisely the skills and career goals for which this program was developed, and the resources of the K24 award would greatly enhance Dr. Criswell's ability to accomplish her goals as a patient-oriented clinical researcher and mentor through the provision of essential resources and relief of patient care and other activities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE MANNOSE-BINDING LECTIN AND AUTOIMMUNITY Principal Investigator & Institution: Ezekowitz, Alan B. Professor & Chief of Pediatrics Services; Cbr Institute for Biomedical Research 800 Huntington Ave Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: The predominant interest of our laboratory is to study the innate immune system in vertebrates and insects. Our focus is to define the structure and function of pattern recognition molecules that appear to selectively recognize the patterns of oligosaccharides that decorate microorganisms from self-glycoproteins. The mannosebinding lectin (MBL) is one such molecule which functions like an ante-antibody and is regarded as a prototypic mammalian pattern recognition molecule. MBL appears to play a role in first line host defense in the lag period that is required to generate a long lasting adaptive immune response. A hallmark of innate immunity is that it is now recognized as a necessary antecedent for the development of an adaptive immune response. Little or no attention has been paid as to whether MBL is able to interact and prime the development of adaptive immunity, in particular systemic lupus erythematosis (SLE), we believe that MBL plays a role B cell homeostasis. The goal of this proposal is to explore this question by making use of unique MBL null mou7se models that we have generated in our laboratory in conjunction with other known lupus prone animal models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ROLE OF COMPLEMENT IN PROTECTION AGAINST SLE Principal Investigator & Institution: Carroll, Michael C. Professor; Cbr Institute for Biomedical Research 800 Huntington Ave Boston, MA 02115 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: Systemic lupus erythematosis (SLE) is a relatively common and incurable autoimmune disorder that affects women 10 fold more than men. The etiology is unknown, but the disease is characterized by autoantibodies specific for nuclear antigens, such as dsDNA histones and ribonuclear proteins. Genetic studies support a critical protective role for the innate immune system, as humans deficient in complement components C1q or C4 almost always develop this disease. To dissect the importance of self-antigen and the complement system in negative regulation of selfreactive B cells, mice bearing a targeted deletion in complement proteins C1q, C4 or the receptor C42 will be examined alone, or in combination with immunoglobulin (Ig)
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transgenes (tg), in three interrelated aims described below. The first aim will test the hypothesis that self-antigen alters the development of B-lymphocytes. Two sub-aims will explore the questions: (i) What is the relative importance of antigen concentration and affinity on B cell receptor (BCR) editing and apoptosis? (ii) Does receptor editing represent re- initiation of RAG gene expression (induction), or is it a dye product of selection or continued expression of the rearrangement complex? The second aim will test the hypothesis that complement C1q, C4 and CD21/CD35 participate in negative selection of developing B cells. The two sub-aims will address: (i) Does deficiency in C1q, C4 or CD21/CD35 alter negative selection? (i) Is CD21/CD35 expression on stroma or B cells important in negative selection? The third aim will test the hypothesis that complement protects from autoimmunity by enhancing clearance of apoptotic material. The two sub-aims will address the questions: (ii) Does expression of C4 in adult C4-/mice restore clearance and protect against auto-antibodies? The overall significance of this project is that it directly addresses a fundamental question regarding the role of complement in protection against autoimmune disease. The results should distinguish whether complement protects by enhancing negative selection of self-reactive Blymphocytes; or if its importance is more in sequestration and clearance of lupus antigens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF FC GAMMA RECEPTORIIB IN B CELL TOLERANCE Principal Investigator & Institution: Mcgaha, Tracy L. Lab/Molecular Genetics; Rockefeller University New York, NY 100216399 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by the applicant): Fc gamma receptor IIB is an important regulator of immuno-reactivity. Genetic disruption of the Fc gamma receptor results in a fulminate, lupus-like disease in the C57BL/6 murine background. The goal of this project is to more closely examine the lupus which arises in these animals to determine the effect that Fc gamma receptor IIB disruption has on the B cell repertoire and on silencing of auto-reactive B cells in the periphery. In addition, these studies investigate the nature of chromatin tolerance in these animals (i.e. is the loss of tolerance reversible or is it a permanent physiological change) by reestablishment of the Fc gamma receptor IIB regulatory pathway in animals with established autoimmunity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THROMBOCYTOPENIA AND THE GENETICS OF SEVERE LUPUS Principal Investigator & Institution: Scofield, R Hal. Associate Professor; Oklahoma Medical Research Foundation Oklahoma City, OK 73104 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Systemic lupus erythematosus (SLE) is a complicated autoimmune disease with a definite genetic predisposition. However, the exploration of SLE genetics is in its infancy. SLE is an extremely complicated clinical illness with a wide range of manifestations. Thus, far the genome scans have been performed using a general SLE phenotype. Use of stratification of a disease population has proven very useful in other diseases. For example, the BCR1 gene was found only when early onset breast cancer was considered among families that also had ovarian cancer. We hypothesize (and the preliminary data demonstrate) that the, as yet unexplored clinical phenotypes of SLE, will prove extremely valuable in uncovering the genetics of SLE. Thrombocytopenia predicts severe disease and death in SLE, making
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the identification of the related genetic risk factors especially important. We selected the 38 pedigrees that had an SLE patient with thrombocytopenia (platelets<100,000 per tile) from a collection of 179 pedigrees multiplex for SLE. Linkages were established at lq2223 (lod-max)=3.71) in the 38 pedigrees and at 11p13 (lod(max) = 5.72) in the 13 AfricanAmerican pedigrees. Nephritis, serositis, neuropsychiatric involvement, autoimmune hemolytic anemia, anti-double stranded DNA and antiphospholipid antibody were associated with thrombocytopenia. Other results show that SLE is more severe in the families with a thrombocytopenic SLE patient, whether or not thrombocytopenia in an individual patient is considered. We have now begun to fine map the 11p13 region. This project will continue to explore the genetics of the severe phenotype of SLE defined by thrombocytopenia. In particular, the PI will concentrate on the statistically powerful finding on chromosome 11lp13, the strongest found to date in SLE. In the first specific aim the genetic interval will be fine mapped with DNA microsatellite markers in order to confirm linkage and narrow the interval. In the second specific aim the PI will search for genetic association with SLE by typing at single nucleotide polymorphisms throughout the defined interval supporting linkage. In Specific Aim 3, the genetic polymorphism(s) responsible for the linkage will be sought by sequencing genes within the now narrowly defined linkage interval. Finally, in specific Aim 4 the PI will assemble a new cohort of families multiplex for SLE such that linkages and associations as well as particular polymorphisms can be prospectively confirmed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOXICOLOGY OF METAL INDUCED IMMUNOPATHOLOGY Principal Investigator & Institution: Lawrence, David A. Research Scientist/Professor/Chief; Wadsworth Center Empire State Plaza Albany, NY 12237 Timing: Fiscal Year 2001; Project Start 01-JUN-1998; Project End 31-MAY-2004 Summary: (Adapted from the investigator's abstract). The long-term goal of this project is to determine the mechanism(s) by which an environmental agent such as lead (Pb) interplays with genetics to influence the onset of an autoimmune disease such as Systemic Lupus Erythematosus (SLE). Susceptibility to SLE is known to be under complex polygenic control and is thought to be influenced by environmental agents capable of modulating the immune system of individuals with a genetic liability. The goal of this proposal is to pursue the hypothesis that environmental toxicants contribute to the triggering and exacerbation of SLE. The focus will be on the effects of Pb on susceptibility to SLE by taking advantage of a new model in New Zealand Mixed (NZM) strains of mice. These recombinant inbred strains were derived from the parental strains of the classic NZB x NZW Fl hybrid female SLE model; the mixtures of susceptibility genes, inherited from the ancestral genomes by recombination and segregation, contribute to phenotypic differences of nephritis, CNS lupus, and other autoimmune phenotypes. The NZM strains, therefore, offer a new way of looking at the effects of the environment on triggering or exacerbating SLE in a closely related set of lupus-prone, H-2 identical strains. The novel advantage is that some NZM strains with partial or low penetrance of autoimmunity may be more informative than mice at the extremes of susceptibility or resistance. The Specific Aims are: (1) determine the effects of Pb exposure on the time course, severity, morphogenesis, and immunopathology of autoimmune immune-complex-mediated nephritis and CNS pathology in selected NZM strains with high, partial, and low penetrance. (2) ascertain effects of Pb on manifestations of B-cell autoimmunity to include strain-specific patterns of anti-dsDNA and anti-chromatin autoantibody profiles, Coombs' positivity (anti-erythrocyte autoantibodies), anti-phospholipid, and B-cell hyperactivity. (3) assess T-cell activation
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and cytokine profiles (IL-2 and IFNg vs IL-4 and IL-5) and accessory cytokine levels (IL1, IL-6 and TNFa) and 4 evaluate the involvement of hormonal patterns in disease modulation. The proposed research will provide basic information on the effects of Pb on SLE susceptibility in individuals with variable numbers of threshold liability genes, in identifying SLE genes, and a general understanding of the extent to which environmental factors may influence autoimmunity and autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UCSF AUTOIMMUNITY CENTER OF EXCELLENCE Principal Investigator & Institution: Wofsy, David; Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The broad aim of this application is to translate advances in immunology and molecular biology into practical, safe, and effective therapies for people with autoimmune diseases. Toward this end, we will participate in collaborative clinical trials of novel immunotherapies, and we will conduct basic research into the mechanisms that lead to autoimmunity as well as the mechanisms that can be harnessed to prevent autoimmunity. This proposal to become an Autoimmunity Center of Excellence consists of a Clinical Center, two basic research projects, and an Immune Function Monitoring Core as described below: Clinical Center (David Wofsy, PI). Investigators involved in this application have extensive experience in the conduct of clinical trials in diverse autoimmune diseases. This application focuses primarily on systemic lupus erythematosus (SLE), multiple sclerosis (MS), and type I diabetes mellitus (IDDM). Two clinical protocols are proposed, both based on basic research conducted at UCSF by participants in this proposal. Protocol 1 is based on the observation that blockade of T cell co-stimulation by CTLA4Ig, in combination with conventional therapy with cyclophosphamide, produces long-lasting benefit in murine lupus. It tests the hypothesis that this approach to therapy will be effective in people with lupus nephritis. Protocol 2 is based on the observation that HMG-CoA inhibitors ('statins') retard murine models for MS. It tests the hypothesis that atorvastatin will prevent progression to MS in patients at high risk. Project I - Activation and functions of regulatory T lymphocytes (Abul Abbas and Jeffrey Bluestone, co-PIs): The principal goals of this project are: (1) to clarify the signals involved in the induction and maintenance of regulatory T cells (Treg); and (2) to understand the mechanisms by which Treg control potentially pathogenic effector cells. Project 2 - Targeting antigenspecific T ceils in SLE (David Daikh, PI): The principal goals of this project are: (1) to use murine models for SLE to clarify the mechanisms of disease, and to understand the basis for the efficacy of specific therapeutic interventions; and (2} to develop novel antigenspecific approaches to the treatment of autoimmune disease in murine models as a prelude to clinical trials in humans. Immune Function Monitoring Core (Lawrence Fong, PI): This core facility will provide the capability for developing and performing cellular and antibody-based immune assays on samples (e.g., blood, lymph node, etc.) derived from patients participating in ACE trials. Assays that will be available include: flow cytometry; MHC/peptide tetramer production and staining; cytokine analysis by ELISA, ELISPOT, and flow; T cell proliferation; and cytotoxicity assays. This core will support the Clinical Center and Project 2. Together, the Clinical Center, individual projects, and Immune Monitoring Core comprise a tightly linked program to bring novel therapies from bench to bedside and to investigate the mechanisms by which these therapies retard autoimmune disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ULTRAVIOLET A LIGHT ON DISEASE ACTIVITY/IMMUNE FUNCTION PATIENTS WITH LUPUS Principal Investigator & Institution: Mcgrath, Hugh J.; Tulane University of Louisiana New Orleans, LA 70118 Timing: Fiscal Year 2001 Summary: The purpose of this study is to determine the effects of long-term low dose ultra-A1 (320-400 nm) light on delayed type hypersensitivity, T-lymphocyte of subset populations, and t-lymphocyte function of normal human subjects as determined by in vitro lymphocyte assays. The same observations will be made on patients with systemic lupus erythematosus and the effects of this light on the laboratory and clinical parameters of SLE will be measured. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: UNIVERSITY OF MICHIGAN RHEUMATIC DISEASES CORE CENTER Principal Investigator & Institution: Fox, David A. Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2001; Project Start 28-SEP-2001; Project End 31-JUL-2006 Summary: The University of Michigan proposes to establish a Rheumatic Disease Core Center. This will be a broadly based effort involving approximately 80 faculty from clinical and basic science departments at the University of Michigan and neighboring institutions. The Center will apply a broad range of research skills, backgrounds, and approaches to investigation of fundamental issues in the etiology and pathogenesis of rheumatic diseases and in development of a scientific basis for novel therapeutics. The Center will focus its activities by grouping investigators in four Major Programs (Model Systems for Innovative Therapeutics, Autoimmunity, Cell and Cytokine Interactions in Organ Inflammation and Damage, and Genetics and Patterns of Gene Expression in the Rheumatic Diseases); and also in Disease Focused Working Groups (Osteoarthritis, Psoriasis/Psoriatic Arthritis, Rheumatoid Arthritis and Systemic Lupus Erythematosis). Activities of the Center will be supported by six Biomedical Core Facilities including Flow Cytometry, Hybridoma, Vector, Transgenic Animal, Protein Structure and DNA Sequencing Cores. UM-RDCC faculty will have access to core services for rheumatic disease-related research at substantially discounted recharge rates. Two Pilot and Feasibility Projected are proposed, each of which is led by new faculty recently recruited to the University of Michigan. The UM-RDCC and its administrative unit will be directed by David A. Fox, M.D., who is experienced in administration of a broadly based Center through more than ten years directing the University of Michigan Multipurpose Arthritis and Musculoskeletal Diseases Center. Rory Marks, M.D., Associate Professor of Rheumatology is proposed as the UM-RDCC Associate Director, with special responsibilities for supervision of the biomedical cores. The Center leadership will maintain close links between the basic research activities of the UMRDCC and expanding clinical investigation in the rheumatic diseases at the University of Michigan. The Center's administrative team will be assisted by an Executive Committee, an Internal Advisory Committee, and an External Scientific Advisor, Dr. Bennis Carson. We have constructed the UM- RDCC to maximally engage the talents and resources of the University of Michigan to focus on basic research in the rheumatic diseases in the rheumatic diseases, so as to achieve substantial progress in improving understanding of etiology, pathogenesis and treatment.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “lupus” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for lupus in the PubMed Central database: •
A genome-wide search for susceptibility genes in human systemic lupus erythematosus sib-pair families. by Gaffney PM, Kearns GM, Shark KB, Ortmann WA, Selby SA, Malmgren ML, Rohlf KE, Ockenden TC, Messner RP, King RA, Rich SS, Behrens TW. 1998 Dec 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24543
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Activation of natural killer T cells in NZB/W mice induces Th1-type immune responses exacerbating lupus. by Zeng D, Liu Y, Sidobre S, Kronenberg M, Strober S. 2003 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=213484
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Amelioration of Lupus-Like Autoimmune Disease in NZB/W F1 Mice after Treatment with a Blocking Monoclonal Antibody Specific for Complement Component C5. by Wang Y, Hu Q, Madri JA, Rollins SA, Chodera A, Matis LA. 1996 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38712
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Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus. by Kaplan D, Ferrari I, Bergami PL, Mahler E, Levitus G, Chiale P, Hoebeke J, Van Regenmortel MH, Levin MJ. 1997 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23357
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B cells, BAFF/zTNF4, TACI, and systemic lupus erythematosus. by Dorner T, Putterman C. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128894
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CD137 costimulatory T cell receptor engagement reverses acute disease in lupusprone NZB x NZW F1 mice. by Foell J, Strahotin S, O'Neil SP, McCausland MM, Suwyn C, Haber M, Chander PN, Bapat AS, Yan XJ, Chiorazzi N, Hoffmann MK, Mittler RS. 2003 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155050
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Control of separate pathogenic autoantibody responses marks MHC gene contributions to murine lupus. by Vyse TJ, Halterman RK, Rozzo SJ, Izui S, Kotzin BL. 1999 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22194
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Defective cAMP-Dependent Phosphorylation of Intact T Lymphocytes in Active Systemic Lupus Erythematosus. by Hasler P, Schultz LA, Kammer GM. 1990 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53608
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Effect of genetic background on the contribution of New Zealand Black loci to autoimmune lupus nephritis. by Rozzo SJ, Vyse TJ, Drake CG, Kotzin BL. 1996 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26374
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Establishment of Monoclonal Anti-Retroviral gp70 Autoantibodies from MRL/lpr Lupus Mice and Induction of Glomerular gp70 Deposition and Pathology by Transfer into Non-Autoimmune Mice. by Tabata N, Miyazawa M, Fujisawa R, Takei YA, Abe H, Hashimoto K. 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111926
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Evidence for a susceptibility gene (SLEH1) on chromosome 11q14 for systemic lupus erythematosus (SLE) families with hemolytic anemia. by Kelly JA, Thompson K, Kilpatrick J, Lam T, Nath SK, Gray-McGuire C, Reid J, Namjou B, Aston CE, Bruner GR, Scofield RH, Harley JB. 2002 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129343
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Genetic Analysis of the NZB Contribution to Lupus-Like Autoimmune Disease in (NZB x NZW)F1 Mice. by Drake CG, Babcock SK, Palmer E, Kotzin BL. 1994 Apr 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43723
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Genetic epidemiology: Systemic lupus erythematosus. by Ahmad YA, Bruce IN. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128907
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Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus. by Graham RR, Langefeld CD, Gaffney PM, Ortmann WA, Selby SA, Baechler EC, Shark KB, Ockenden TC, Rohlf KE, Moser KL, Brown WM, Gabriel SE, Messner RP, King RA, Horak P, Elder JT, Stuart PE, Rich SS, Behrens TW. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64842
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Genetic reconstitution of systemic lupus erythematosus immunopathology with polycongenic murine strains. by Morel L, Croker BP, Blenman KR, Mohan C, Huang G, Gilkeson G, Wakeland EK. 2000 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18697
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Genome scan of human systemic lupus erythematosus: Evidence for linkage on chromosome 1q in African-American pedigrees. by Moser KL, Neas BR, Salmon JE, Yu H, Gray-McGuire C, Asundi N, Bruner GR, Fox J, Kelly J, Henshall S, Bacino D, Dietz M, Hogue R, Koelsch G, Nightingale L, Shaver T, Abdou NI, Albert DA, Carson C, Petri M, Treadwell EL, James JA, Harley JB. 1998 Dec 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24542
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Heritable Major Histocompatibility Complex Class II-Associated Differences in Production of Tumor Necrosis Factor [alpha]: Relevance to Genetic Predisposition to
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Systematic Lupus Erythematosus. by Jacob CO, Fronek Z, Lewis GD, Koo M, Hansen JA, McDevitt HO. 1990 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53445 •
IFN-gamma transgenic mice: clues to the pathogenesis of systemic lupus erythematosus? by Seery JP. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128871
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Immunophilins, Refsum disease, and lupus nephritis: The peroxisomal enzyme phytanoyl-COA [alpha]-hydroxylase is a new FKBP-associated protein. by Chambraud B, Radanyi C, Camonis JH, Rajkowski K, Schumacher M, Baulieu EE. 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26744
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Impaired apoptosis, extended duration of immune responses, and a lupus-like autoimmune disease in IEX-1-transgenic mice. by Zhang Y, Schlossman SF, Edwards RA, Ou CN, Gu J, Wu MX. 2002 Jan 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117399
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In vivo Expression of a Single Viral DNA-Binding Protein Generates Systemic Lupus Erythematosus-Related Autoimmunity to Double-Stranded DNA and Histones. by Moens U, Seternes O, Hey AW, Silsand Y, Traavik T, Johansen B, Rekvig OP. 1995 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40364
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Induction of Anti-Phospholipid Syndrome in Naive Mice with Mouse Lupus Monoclonal and Human Polyclonal Anti-Cardiolipin Antibodies. by Blank M, Cohen J, Toder V, Shoenfeld Y. 1991 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51386
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Junctional Region Sequences of T-Cell Receptor [beta]-Chain Genes Expressed by Pathogenic Anti-DNA Autoantibody-Inducing Helper T Cells from Lupus Mice: Possible Selection by Cationic Autoantigens. by Adams S, Leblanc P, Datta SK. 1991 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53116
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Lupus Susceptibility Loci in New Zealand Mice. by Kono DH, Burlingame RW, Owens DG, Kuramochi A, Balderas RS, Balomenos D, Theofilopoulos AN. 1994 Oct 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44979
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Mitral Valve Replacement and Repair: Report of 5 Patients with Systemic Lupus Erythematosus. by Hakim JP, Mehta A, Jain AC, Murray GF. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101131
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Modulation of murine systemic lupus erythematosus with peptides based on complementarity determining regions of a pathogenic anti-DNA monoclonal antibody. by Waisman A, Ruiz PJ, Israeli E, Eilat E, Konen-Waisman S, Zinger H, Dayan M, Mozes E. 1997 Apr 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20773
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p70 Lupus Autoantigen Binds the Enhancer of the T-Cell Receptor [beta]- Chain Gene. by Messier H, Fuller T, Mangal S, Brickner H, Igarashi S, Gaikwad J, Fotedar R, Fotedar A. 1993 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46160
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Pathogenic Anti-DNA Autoantibody-Inducing T Helper Cell Lines from Patients with Active Lupus Nephritis: Isolation of CD4-8- T Helper Cell Lines That Express the [gamma][delta] T-Cell Antigen Receptor. by Rajagopalan S, Zordan T, Tsokos GC, Datta SK. 1990 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54674
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Perturbations in the impact of mutational activity on V[lambda] genes in systemic lupus erythematosus. by Dorner T, Kaschner S, Hansen A, Pruss A, Lipsky PE. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64848
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Reactivity of Sera from Systemic Lupus Erythematosus and Sjogren's Syndrome Patients with Peptides Derived from Human Immunodeficiency Virus p24 Capsid Antigen. by Deas JE, Liu LG, Thompson JJ, Sander DM, Soble SS, Garry RF, Gallaher WR. 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=121355
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Representational difference analysis in a lupus-prone mouse strain results in the identification of an unstable region of the genome on chromosome 11. by Fu G, Haywood ME, Morley BJ. 2002 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=101347
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Role of the major histocompatibility complex class II Ea gene in lupus susceptibility in mice. by Ibnou-Zekri N, Iwamoto M, Fossati L, McConahey PJ, Izui S. 1997 Dec 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25083
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Serum S100B Levels in Patients with Lupus Erythematosus: Preliminary Observation. by Portela LV, Brenol JC, Walz R, Bianchin M, Tort AB, Canabarro UP, Beheregaray S, Marasca JA, Xavier RM, Neto EC, Goncalves CA, Souza DO. 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=119880
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Somatic Diversification in the Heavy Chain Variable Region Genes Expressed by Human Autoantibodies Bearing a Lupus-Associated Nephritogenic Anti-DNA Idiotype. by Demaison C, Chastagner P, Theze J, Zouali M. 1994 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42979
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Surface Blebs on Apoptotic Cells are Sites of Enhanced Procoagulant Activity: Implications for Coagulation Events and Antigenic Spread in Systemic Lupus Erythematosus. by Casciola-Rosen L, Rosen A, Petri M, Schlissel M. 1996 Feb 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39992
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The Fas Protein is Expressed at High Levels on CD4+CD8+ Thymocytes and Activated Mature Lymphocytes in Normal Mice but not in the Lupus-Prone Strain, MRL lpr/lpr. by Drappa J, Brot N, Elkon KB. 1993 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47770
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The major murine systemic lupus erythematosus susceptibility locus, Sle1, is a cluster of functionally related genes. by Morel L, Blenman KR, Croker BP, Wakeland EK. 2001 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29335
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The mechanism by which a peptide based on complementarity-determining region-1 of a pathogenic anti-DNA auto-Ab ameliorates experimental systemic lupus erythematosus. by Eilat E, Dayan M, Zinger H, Mozes E. 2001 Jan 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14723
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The role of IFN-gamma in systemic lupus erythematosus: a challenge to the Th1/Th2 paradigm in autoimmunity. by Theofilopoulos AN, Koundouris S, Kono DH, Lawson BR. 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128889
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The VH gene repertoire of splenic B cells and somatic hypermutation in systemic lupus erythematosus. by Fraser NL, Rowley G, Field M, Stott DI. 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165037
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Trichostatin A reverses skewed expression of CD154, interleukin-10, and interferon[gamma] gene and protein expression in lupus T cells. by Mishra N, Brown DR, Olorenshaw IM, Kammer GM. 2001 Feb 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30189
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Very Long Charge Runs in Systemic Lupus Erythematosus-Associated Autoantigens. by Brendel V, Dohlman J, Blaisdell BE, Karlin S. 1991 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51054
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with lupus, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “lupus” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for lupus (hyperlinks lead to article summaries):
6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A 12-year-old girl with hemolytic uremic syndrome as initial symptom of systemic lupus erythematosus and a literature review. Author(s): Kawasaki Y, Suzuki J, Nozawa R, Suzuki S, Suzuki H. Source: American Journal of Nephrology. 2002 September-December; 22(5-6): 576-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381963&dopt=Abstract
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A case of lupus vulgaris with unusual location. Author(s): Senol M, Ozcan A, Mizrak B, Turgut AC, Karaca S, Kocer H. Source: The Journal of Dermatology. 2003 July; 30(7): 566-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928550&dopt=Abstract
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A case of lymphocytic infundibuloneurohypophysitis associated with systemic lupus erythematosus. Author(s): Hashimoto K, Asaba K, Tamura K, Takao T, Nakamura T. Source: Endocr J. 2002 December; 49(6): 605-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625409&dopt=Abstract
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A case of nodular cutaneous lupus mucinosis. Author(s): Terao H, Moroi Y, Urabe K, Koga T, Furue M. Source: The Journal of Dermatology. 2003 April; 30(4): 341-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707473&dopt=Abstract
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A case of subcutaneous phaeohyphomycotic cyst due to Exophiala jeanselmei complicated with systemic lupus erythematosus. Author(s): Murayama N, Takimoto R, Kawai M, Hiruma M, Takamori K, Nishimura K. Source: Mycoses. 2003 April; 46(3-4): 145-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870205&dopt=Abstract
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A case of thrombotic microangiopathy complicated with systemic lupus erythematosus. Author(s): Ohashi N, Yamamoto T, Kanno D, Fujigaki Y, Yonemura K, Hishida A. Source: The American Journal of the Medical Sciences. 2003 August; 326(2): 102-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920443&dopt=Abstract
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A lupus-like syndrome associated with infliximab therapy. Author(s): Klapman JB, Ene-Stroescu D, Becker MA, Hanauer SB. Source: Inflammatory Bowel Diseases. 2003 May; 9(3): 176-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792223&dopt=Abstract
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A major susceptibility locus for systemic lupus erythemathosus maps to chromosome 1q31. Author(s): Johanneson B, Lima G, von Salome J, Alarcon-Segovia D, Alarcon-Riquelme ME; Collaborative Group on the Genetics of SLE, The BIOMED II Collaboration on the Genetics of SLE and Sjogrens syndrome. Source: American Journal of Human Genetics. 2002 November; 71(5): 1060-71. Epub 2002 October 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373647&dopt=Abstract
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A neuroimaging follow up study of a patient with juvenile central nervous system systemic lupus erythematosus. Author(s): Steens SC, Bosma GP, ten Cate R, Doornbos J, Kros JM, Laan LA, SteupBeekman GM, van Buchem MA, Huizinga TW. Source: Annals of the Rheumatic Diseases. 2003 June; 62(6): 583-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759301&dopt=Abstract
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A nonsense mutation in exon 2 of the DNase I gene is not present in UK subjects with systemic lupus erythematosus and Graves' disease: Comment on the article by Rood et al. Author(s): Simmonds MJ, Heward JM, Kelly MA, Allahabadia A, Foxall H, Gordon C, Franklyn JA, Gough SC. Source: Arthritis and Rheumatism. 2002 November; 46(11): 3109-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428267&dopt=Abstract
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A novel polymorphism of the human APRIL gene is associated with systemic lupus erythematosus. Author(s): Koyama T, Tsukamoto H, Masumoto K, Himeji D, Hayashi K, Harada M, Horiuchi T. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 980-5. Epub 2003 March 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730512&dopt=Abstract
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A practice approach for identifying previously unsuspected environmental contributors to systemic lupus erythematosus and other complex diseases. Author(s): Foster MW, Aston CE. Source: Environmental Health Perspectives. 2003 April; 111(4): 593-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676621&dopt=Abstract
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A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis. Author(s): Boumpas DT, Furie R, Manzi S, Illei GG, Wallace DJ, Balow JE, Vaishnaw A; BG9588 Lupus Nephritis Trial Group. Source: Arthritis and Rheumatism. 2003 March; 48(3): 719-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632425&dopt=Abstract
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Abdominal pain as the initial and sole clinical presenting feature of systemic lupus erythematosus. Author(s): Chung HV, Ramji A, Davis JE, Chang S, Reid GD, Salh B, Freeman HJ, Yoshida EM. Source: Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie. 2003 February; 17(2): 111-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605248&dopt=Abstract
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Abnormal brain diffusivity in patients with neuropsychiatric systemic lupus erythematosus. Author(s): Bosma GP, Huizinga TW, Mooijaart SP, Van Buchem MA. Source: Ajnr. American Journal of Neuroradiology. 2003 May; 24(5): 850-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748084&dopt=Abstract
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Abnormal regional cerebral blood flow found by technetium-99m ethyl cysteinate dimer brain single photon emission computed tomography in systemic lupus erythematosus patients with normal brain MRI findings. Author(s): Chen JJ, Yen RF, Kao A, Lin CC, Lee CC. Source: Clinical Rheumatology. 2002 November; 21(6): 516-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447638&dopt=Abstract
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Acquired type 3-like von Willebrand syndrome preceded full-blown systemic lupus erythematosus. Author(s): Niiya M, Niiya K, Takazawa Y, Hayashi Y, Tanio Y, Kushiro M, Tanimizu M, Hasegawa H, Tanimoto M. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 2002 June; 13(4): 361-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032403&dopt=Abstract
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Activation of the Ets transcription factor Elf-1 requires phosphorylation and glycosylation: defective expression of activated Elf-1 is involved in the decreased TCR zeta chain gene expression in patients with systemic lupus erythematosus. Author(s): Tsokos GC, Nambiar MP, Juang YT. Source: Annals of the New York Academy of Sciences. 2003 April; 987: 240-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727645&dopt=Abstract
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Active idiopathic Systemic Lupus Erythematosus in a 94-year-old woman necessitating immunosuppressive therapy. Author(s): Madge SN, Donegan C. Source: Age and Ageing. 2002 November; 31(6): 489-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446306&dopt=Abstract
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Acute graft-versus-host disease (aGVHD) presenting with an acquired lupus anticoagulant. Author(s): Kharfan-Dabaja MA, Morgensztern D, Santos E, Goodman M, Fernandez HF. Source: Bone Marrow Transplantation. 2003 January; 31(2): 129-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621495&dopt=Abstract
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Acute type A aortic dissection in a patient with systemic lupus erythematosus. Author(s): Aoyagi S, Akashi H, Otsuka H, Sakashita H, Okazaki T, Tayama K. Source: Japanese Heart Journal. 2002 September; 43(5): 567-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452314&dopt=Abstract
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Adaptation to chronic pain in systemic lupus erythematosus: applicability of the multidimensional pain inventory. Author(s): Greco CM, Rudy TE, Manzi S. Source: Pain Medicine (Malden, Mass.). 2003 March; 4(1): 39-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873277&dopt=Abstract
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Allelic frequency of the MCP-1 promoter -2518 polymorphism in the Korean population and in Korean patients with rheumatoid arthritis, systemic lupus erythematosus and adult-onset Still's disease. Author(s): Hwang SY, Cho ML, Park B, Kim JY, Kim YH, Min DJ, Min JK, Kim HY. Source: European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics. 2002 October; 29(5): 413-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358851&dopt=Abstract
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Allergic diseases in systemic lupus erythematosus: prevalence and immunological considerations. Author(s): Sekigawa I, Yoshiike T, Iida N, Hashimoto H, Ogawa H. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 117-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673903&dopt=Abstract
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Amiodarone-induced systemic lupus erythematosus. Author(s): Kundu AK. Source: J Assoc Physicians India. 2003 February; 51: 216-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725272&dopt=Abstract
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Amyloid deposition is frequently observed in skin lesions of hypertrophic lupus erythematosus. Author(s): Khan MA, Maruno M, Khaskhely NM, Uezato H, Nonaka S. Source: The Journal of Dermatology. 2002 October; 29(10): 633-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432994&dopt=Abstract
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An unusual cause of loin pain in a patient with systemic lupus erythematosus. Author(s): Yoon KH, Goh PS. Source: The Journal of Rheumatology. 2003 March; 30(3): 634-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610831&dopt=Abstract
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Analysis of clinical and immunological features of patients with systemic lupus erythematosus complicated by hepatitis C virus infection. Author(s): Qin CL, Yang QY, Liao YX. Source: Di Yi June Yi Da Xue Xue Bao. 2002 October; 22(10): 939-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12377627&dopt=Abstract
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Analysis of human leukocyte antigens class II-DR in Brazilian children and adolescents with systemic lupus erythematosus. Author(s): Liphaus Bde L, Goldberg AC, Kiss MH, Silva CA. Source: Revista Do Hospital Das Clinicas. 2002 November-December; 57(6): 277-82. Epub 2003 February 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612760&dopt=Abstract
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Analysis of polymorphisms affecting immune complex handling in systemic lupus erythematosus. Author(s): Sullivan KE, Jawad AF, Piliero LM, Kim N, Luan X, Goldman D, Petri M. Source: Rheumatology (Oxford, England). 2003 March; 42(3): 446-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626795&dopt=Abstract
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Antagonist of monocyte chemoattractant protein 1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice. Author(s): Hasegawa H, Kohno M, Sasaki M, Inoue A, Ito MR, Terada M, Hieshima K, Maruyama H, Miyazaki J, Yoshie O, Nose M, Fujita S. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2555-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130475&dopt=Abstract
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Anticancer drug shows promise against lupus. Author(s): Foubister V. Source: Drug Discovery Today. 2003 April 15; 8(8): 333-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681930&dopt=Abstract
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Anti-chromatin antibodies in systemic lupus erythematosus: a useful marker for lupus nephropathy. Author(s): Cervera R, Vinas O, Ramos-Casals M, Font J, Garcia-Carrasco M, Siso A, Ramirez F, Machuca Y, Vives J, Ingelmo M, Burlingame RW. Source: Annals of the Rheumatic Diseases. 2003 May; 62(5): 431-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695155&dopt=Abstract
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Antidouble-stranded DNA isotypes in lupus erythematosus patients with prevalent cutaneous presentation. Author(s): Parodi A, Drosera M, Barbieri LB, Babbini G, Rebora A. Source: The British Journal of Dermatology. 2002 October; 147(4): 754-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366424&dopt=Abstract
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Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis. Author(s): Alba P, Bento L, Cuadrado MJ, Karim Y, Tungekar MF, Abbs I, Khamashta MA, D'Cruz D, Hughes GR. Source: Annals of the Rheumatic Diseases. 2003 June; 62(6): 556-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759294&dopt=Abstract
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Antiendothelial cell antibodies in systemic lupus erythematosus. Author(s): Renaudineau Y, Dugue C, Dueymes M, Youinou P. Source: Autoimmunity Reviews. 2002 December; 1(6): 365-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848993&dopt=Abstract
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Antiguanosine antibodies in murine and human lupus have the internal image of Gbinding proteins. Author(s): Colburn KK, Wong AL, Weisbart RH, Green LM. Source: The Journal of Rheumatology. 2003 May; 30(5): 993-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734894&dopt=Abstract
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Antinuclear antibody-negative systemic lupus erythematosus: revisited. Author(s): Kaur S, Thami GP. Source: Indian J Pediatr. 2003 February; 70(2): 185-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661819&dopt=Abstract
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Anti-nucleosome antibodies and T-cell response in systemic lupus erythematosus. Author(s): Fournel S, Muller S. Source: Annales De Medecine Interne. 2002 December; 153(8): 513-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610425&dopt=Abstract
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Antiphospholipid antibodies in Chilean patients with systemic lupus erythematosus. Author(s): Palomo I, Pereira J, Alarcon M, Larrain AM, Pinochet C, Vasquez M, Velez MT, Leon M, Espinola R, Pierangeli S. Source: The Journal of Laboratory and Clinical Medicine. 2002 November; 140(5): 336-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434135&dopt=Abstract
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Anti-ribosomal antibodies from lupus patients bind DNA. Author(s): Caponi L, Chimenti D, Pratesi F, Migliorini P. Source: Clinical and Experimental Immunology. 2002 December; 130(3): 541-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452847&dopt=Abstract
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Antisense cyclic adenosine 5'-monophosphate response element modulator upregulates IL-2 in T cells from patients with systemic lupus erythematosus. Author(s): Tenbrock K, Juang YT, Gourley MF, Nambiar MP, Tsokos GC. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 October 15; 169(8): 4147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370343&dopt=Abstract
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Anti-SSB/La is one of the antineutrophil autoantibodies responsible for neutropenia and functional impairment of polymorphonuclear neutrophils in patients with systemic lupus erythematosus. Author(s): Hsieh SC, Yu HS, Lin WW, Sun KH, Tsai CY, Huang DF, Tsai YY, Yu CL. Source: Clinical and Experimental Immunology. 2003 March; 131(3): 506-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605705&dopt=Abstract
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Anti-TNF-alpha-induced systemic lupus syndrome. Author(s): Debandt M, Vittecoq O, Descamps V, Le Loet X, Meyer O. Source: Clinical Rheumatology. 2003 February; 22(1): 56-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605321&dopt=Abstract
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Antitopoisomerase I antibody in patients with systemic lupus erythematosus/sicca syndrome without a concomitant scleroderma: two case reports. Author(s): Al Attia HM, D'Souza MS. Source: Clinical Rheumatology. 2003 February; 22(1): 70-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605324&dopt=Abstract
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Apoptosis of CD34+ cells after incubation with sera of leukopenic patients with systemic lupus erythematosus. Author(s): Tiefenthaler M, Bacher N, Linert H, Muhlmann O, Hofer S, Sepp N, Amberger A, Geisen F, Obermoser G, Konwalinka G. Source: Lupus. 2003; 12(6): 471-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873050&dopt=Abstract
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Assessment of damage in juvenile-onset systemic lupus erythematosus: a multicenter cohort study. Author(s): Ravelli A, Duarte-Salazar C, Buratti S, Reiff A, Bernstein B, MaldonadoVelazquez MR, Beristain-Manterola R, Maeno N, Takei S, Gerloni V, Spencer CH, Pratsidou-Gertsi P, Ruperto N, Pistorio A, Martini A. Source: Arthritis and Rheumatism. 2003 August 15; 49(4): 501-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12910556&dopt=Abstract
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Association of peripheral lymphadenopathy with anti-Ro and anti-La antibodies in a family with systemic lupus erythematosus. Author(s): Bukiej A, Undas A, Pituch-Noworolska A, Chmielewska A, Dyczek A, Musial J. Source: Scandinavian Journal of Rheumatology. 2003; 32(1): 52-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635947&dopt=Abstract
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Association of systemic lupus erythematosus and hypermobility. Author(s): Guma M, Olive A, Roca J, Forcada J, Duro JC, Holgado S, Casado E, Mezquiriz X, Tena X. Source: Annals of the Rheumatic Diseases. 2002 November; 61(11): 1024-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379529&dopt=Abstract
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Association of the TAP2*Bky2 allele with presence of SS-A/Ro and other autoantibodies in Japanese patients with systemic lupus erythematosus. Author(s): Kanagawa S, Morinobu A, Koshiba M, Kageyama G, Hayashi N, Yoshino S, Tokano Y, Hashimoto H, Kumagai S. Source: Lupus. 2003; 12(4): 258-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729048&dopt=Abstract
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Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study. Author(s): Vlachoyiannopoulos PG, Kanellopoulos PG, Ioannidis JP, Tektonidou MG, Mastorakou I, Moutsopoulos HM. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 645-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709540&dopt=Abstract
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Atherosclerosis, oxidative stress and auto-antibodies in systemic lupus erythematosus and primary antiphospholipid syndrome. Author(s): Alves JD, Ames PR. Source: Immunobiology. 2003; 207(1): 23-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638899&dopt=Abstract
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Autoantibodies against granulocyte colony-stimulating factor in Felty's syndrome and neutropenic systemic lupus erythematosus. Author(s): Hellmich B, Csernok E, Schatz H, Gross WL, Schnabel A. Source: Arthritis and Rheumatism. 2002 September; 46(9): 2384-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355486&dopt=Abstract
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Autoantibodies and glomerulonephritis in systemic lupus erythematosus. Author(s): Fu SM, Castillo JD, Deshmukh US, Lewis JE, Waters ST, Gaskin F. Source: Lupus. 2003; 12(3): 175-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708777&dopt=Abstract
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Autoantibodies directed against ribosomal proteins in systemic lupus erythematosus and rheumatoid arthritis: a comparative study. Author(s): Desbos A, Gonzalo P, Monier JC, Tebib J, Reboud JP, Perrier H, Bienvenu J, Fabien N. Source: Autoimmunity. 2002 November; 35(7): 427-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685870&dopt=Abstract
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Autoantibodies directed against the amino-terminal domain I of human calpastatin (ACAST-DI Ab) in connective tissue diseases. High levels of ACAST-DI Ab are associated with vasculitis in lupus. Author(s): Saulot V, Vittecoq O, Salle V, Drouot L, Legoedec J, Le Loet X, Godin M, Ducroix JP, Menard JF, Tron F, Gilbert D. Source: Journal of Autoimmunity. 2002 August-September; 19(1-2): 55-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367559&dopt=Abstract
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Autoantibodies to dsDNA, Ro/SSA, and La/SSB in systemic lupus erythematosus. Author(s): Chien JW, Lin CY. Source: Adv Clin Chem. 2003; 37: 129-72. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619707&dopt=Abstract
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Autoantibodies to lipoprotein lipase and dyslipidemia in systemic lupus erythematosus. Author(s): Reichlin M, Fesmire J, Quintero-Del-Rio AI, Wolfson-Reichlin M. Source: Arthritis and Rheumatism. 2002 November; 46(11): 2957-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428237&dopt=Abstract
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Autoimmune hemolityc anemia after treatment of severe systemic lupus erythematosus with high-dose chemotherapy and autotransplantation of selected peripheral hematopoietic progenitors. Author(s): Besalduch J, Bargay J, Buades J, Galmes A, Morey M, Sampol A. Source: Haematologica. 2003 February; 88(2): Ecr01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604425&dopt=Abstract
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Autoimmune responses to proliferating cell nuclear antigen multiprotein complexes involved in cell proliferation are strongly associated with their structure and biologic function in patients with systemic lupus erythematosus. Author(s): Kogure T, Takasaki Y, Takeuchi K, Yamada H, Nawata M, Ikeda K, Matsushita M, Matsudaira R, Kaneda K, Terasawa K, Hashimoto H. Source: Arthritis and Rheumatism. 2002 November; 46(11): 2946-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428236&dopt=Abstract
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B cell anergy and systemic lupus erythematosus. Author(s): Seo SJ, Mandik-Nayak L, Erikson J. Source: Curr Dir Autoimmun. 2003; 6: 1-20. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408044&dopt=Abstract
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B cell loss leading to remission in severe systemic lupus erythematosus. Author(s): Tarrant TK, Frazer DH, Aya-Ay JP, Patel DD. Source: The Journal of Rheumatology. 2003 February; 30(2): 412-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563705&dopt=Abstract
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B cells underpin lupus immunopathology. Author(s): Youinou P, Lydyard PM, Mageed RA. Source: Lupus. 2002; 11(1): 1-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898912&dopt=Abstract
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B cells, BAFF/zTNF4, TACI, and systemic lupus erythematosus. Author(s): Dorner T, Putterman C. Source: Arthritis Research. 2001; 3(4): 197-9. Epub 2001 March 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438034&dopt=Abstract
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B lymphocyte stimulator protein levels in systemic lupus erythematosus and other diseases. Author(s): Stohl W. Source: Curr Rheumatol Rep. 2002 August; 4(4): 345-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126587&dopt=Abstract
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Barriers to treatment adherence among African American and white women with systemic lupus erythematosus. Author(s): Mosley-Williams A, Lumley MA, Gillis M, Leisen J, Guice D. Source: Arthritis and Rheumatism. 2002 December 15; 47(6): 630-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522837&dopt=Abstract
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Bartonella henselae: association with the development of transient lupus anticoagulant and asymptomatic prolongation of activated partial thromboplastin time. Author(s): Economou M, Lithoxopoulou M, Aivazis V, Tsakalidis C, AthanassiouMetaxa M. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(2): 149. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693573&dopt=Abstract
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Baseline characteristics of a multiethnic lupus cohort: PROFILE. Author(s): Alarcon GS, McGwin G Jr, Petri M, Reveille JD, Ramsey-Goldman R, Kimberly RP; PROFILE Study Group. Source: Lupus. 2002; 11(2): 95-101. Erratum In: Lupus 2002; 11(6): 402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958584&dopt=Abstract
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Beneficial effects of a polyamine biosynthesis inhibitor on lupus in MRL-lpr/lpr mice. Author(s): Thomas TJ, Messner RP. Source: Clinical and Experimental Immunology. 1989 November; 78(2): 239-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412756&dopt=Abstract
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Benefits of leflunomide in systemic lupus erythematosus: a pilot observational study. Author(s): Remer CF, Weisman MH, Wallace DJ. Source: Lupus. 2001; 10(7): 480-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480845&dopt=Abstract
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Benzodiazepine library yields lupus target. Author(s): Habeck M. Source: Drug Discovery Today. 2002 December 15; 7(24): 1193-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546994&dopt=Abstract
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Beta2-glycoprotein I dependent anticardiolipin antibodies and lupus anticoagulant in patients with recurrent pregnancy loss. Author(s): Kumar KS, Jyothy A, Prakash MS, Rani HS, Reddy PP. Source: Journal of Postgraduate Medicine. 2002 January-March; 48(1): 5-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12082318&dopt=Abstract
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Bilateral optic neuritis as first manifestation of systemic lupus erythematosus. Author(s): Im CY, Kim SS, Kim HK. Source: Korean J Ophthalmol. 2002 June; 16(1): 52-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12162519&dopt=Abstract
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Binding of rheumatoid and lupus synovial fluids and sera-derived human IgG rheumatoid factor to degalactosylated IgG. Author(s): Chou CT. Source: Archives of Medical Research. 2002 November-December; 33(6): 541-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505099&dopt=Abstract
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Biological treatments for systemic lupus erythematosus. Author(s): Isenberg D, Leckie MJ. Source: Scandinavian Journal of Rheumatology. 2002; 31(4): 187-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369648&dopt=Abstract
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Bone mineral density in juvenile systemic lupus erythematosus. Author(s): Castro TC, Terreri MT, Szejnfeld VL, Castro CH, Fisberg M, Gabay M, Hilario MO. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2002 October; 35(10): 1159-63. Epub 2002 October 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424488&dopt=Abstract
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Bone mineral density in systemic lupus erythematosus and its relation to age at disease onset, plasmatic estradiol and immunosuppressive therapy. Author(s): Coimbra IB, Costallat LT. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2003 February; 70(1): 40-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639616&dopt=Abstract
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Bone mineral density in women with systemic lupus erythematosus. Author(s): Bhattoa HP, Bettembuk P, Balogh A, Szegedi G, Kiss E. Source: Clinical Rheumatology. 2002 May; 21(2): 135-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086164&dopt=Abstract
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Bone mineral density, biochemical markers of bone turnover, and hormonal status in men with systemic lupus erythematosus. Author(s): Bhattoa HP, Kiss E, Bettembuk P, Balogh A. Source: Rheumatology International. 2001 November; 21(3): 97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11765229&dopt=Abstract
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Brachial endothelial function is impaired in patients with systemic lupus erythematosus. Author(s): Lima DS, Sato EI, Lima VC, Miranda F Jr, Hatta FH. Source: The Journal of Rheumatology. 2002 February; 29(2): 292-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842823&dopt=Abstract
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Brain study using magnetic resonance imaging and proton MR spectroscopy in pediatric onset systemic lupus erythematosus. Author(s): Mortilla M, Ermini M, Nistri M, Dal Pozzo G, Falcini F. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673905&dopt=Abstract
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Brodie's abscess of the proximal femoral epiphysis in an adult woman with systemic lupus erythematosus. Author(s): Miyanishi K, Yamamoto T, Irisa T, Jingushi S, Noguchi Y, Iwamoto Y. Source: Archives of Orthopaedic and Trauma Surgery. 2002 June; 122(5): 311-4. Epub 2002 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12070656&dopt=Abstract
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Bromocriptine treatment of systemic lupus erythematosus. Author(s): Walker SE. Source: Lupus. 2001; 10(10): 762-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721704&dopt=Abstract
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Budd-Chiari syndrome associated with systemic lupus erithematosus: diagnostic imaging and percutaneous treatment. Author(s): Rizzati R, Sala S, Tilli M, Marri I, Galeotti R. Source: Radiol Med (Torino). 2003 May-June; 105(5-6): 519-23. English, Italian. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949464&dopt=Abstract
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Bullous systemic lupus erythematosus with milia and calcinosis. Author(s): Eckman JA, Mutasim DF. Source: Cutis; Cutaneous Medicine for the Practitioner. 2002 July; 70(1): 31-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184671&dopt=Abstract
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C4A deficiency and elevated level of immune complexes: the mechanism behind increased susceptibility to systemic lupus erythematosus. Author(s): Traustadottir KH, Sigfusson A, Steinsson K, Erlendsson K. Source: The Journal of Rheumatology. 2002 November; 29(11): 2359-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415592&dopt=Abstract
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Can recombinant anti-hepatitis B vaccine be a cause of systemic lupus erythematosus? Author(s): Fineschi S. Source: Lupus. 2001; 10(11): 830. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789497&dopt=Abstract
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Can the weighted criteria improve our ability to capture a larger number of lupus patients into observational and interventional studies? A comparison with the American College of Rheumatology criteria. Author(s): Sanchez ML, Alarcon GS, McGwin G Jr, Fessler BJ, Kimberly RP. Source: Lupus. 2003; 12(6): 468-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873049&dopt=Abstract
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Cardiac valvular abnormalities are frequent in systemic lupus erythematosus patients with manifest arterial disease. Author(s): Jensen-Urstad K, Svenungsson E, de Faire U, Silveira A, Witztum JL, Hamsten A, Frostegard J. Source: Lupus. 2002; 11(11): 744-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475005&dopt=Abstract
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Cardiovascular autonomic function in systemic lupus erythematosus. Author(s): Hogarth MB, Judd L, Mathias CJ, Ritchie J, Stephens D, Rees RG. Source: Lupus. 2002; 11(5): 308-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090566&dopt=Abstract
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Cardiovascular risk factor screening in systemic lupus erythematosus. Author(s): Al-Herz A, Ensworth S, Shojania K, Esdaile JM. Source: The Journal of Rheumatology. 2003 March; 30(3): 493-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610807&dopt=Abstract
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Cardiovascular risk in systemic lupus erythematosus--evidence of increased oxidative stress and dyslipidaemia. Author(s): Nuttall SL, Heaton S, Piper MK, Martin U, Gordon C. Source: Rheumatology (Oxford, England). 2003 June; 42(6): 758-62. Epub 2003 February 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730535&dopt=Abstract
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Case study: effectiveness of plasma exchange in an adolescent with systemic lupus erythematosus and catatonia. Author(s): Perisse D, Amoura Z, Cohen D, Saintigny P, Mekhloufi F, Mazet P, Piette JC. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 April; 42(4): 497-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649638&dopt=Abstract
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Casein is an essential cofactor in autoantibody reactivity directed against the Cterminal SmD1 peptide AA 83-119 in systemic lupus erythematosus. Author(s): Riemekasten G, Marell J, Hentschel C, Klein R, Burmester GR, Schoessler W, Hiepe F. Source: Immunobiology. 2002 December; 206(5): 537-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607729&dopt=Abstract
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Causes of death and prognostic factors in Thai patients with systemic lupus erythematosus. Author(s): Kasitanon N, Louthrenoo W, Sukitawut W, Vichainun R. Source: Asian Pac J Allergy Immunol. 2002 June; 20(2): 85-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403192&dopt=Abstract
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Celecoxib-induced lupus-like syndrome. Author(s): Poza-Guedes P, Gonzalez-Perez R, Canto G. Source: Rheumatology (Oxford, England). 2003 July; 42(7): 916-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826720&dopt=Abstract
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Central nervous system involvement in neonatal lupus erythematosus. Author(s): Prendiville JS, Cabral DA, Poskitt KJ, Au S, Sargent MA. Source: Pediatric Dermatology. 2003 January-February; 20(1): 60-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558850&dopt=Abstract
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Central nervous system lupus and pregnancy: 11-year experience at a single center. Author(s): El-Sayed YY, Lu EJ, Genovese MC, Lambert RE, Chitkara U, Druzin ML. Source: J Matern Fetal Neonatal Med. 2002 August;12(2):99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420839&dopt=Abstract
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Central nervous system manifestations after steroid pulse therapy in systemic lupus erythematosus. Author(s): Tabata Y, Ichiro K, Kawamura N, Okano M, Kobayashi K. Source: European Journal of Pediatrics. 2002 September; 161(9): 503-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418456&dopt=Abstract
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Cerebral blood flow in systemic lupus erythematosus. Author(s): Koseda-Dragan M, Lass P, Hebanowski M. Source: Lupus. 2001; 10(7): 519-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480854&dopt=Abstract
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Cerebral calcifications in an elderly lupus patient. Author(s): Filloux V, Marotte H, Miossec P. Source: Annals of the Rheumatic Diseases. 2003 March; 62(3): 283-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594129&dopt=Abstract
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Cerebral lupus in patients whilst on treatment for lupus nephritis with cyclosporine. Author(s): Hussein M, Mooij J, Roujouleh H. Source: Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia. 2003 January; 10(1): 104-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464536&dopt=Abstract
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Characterization of CD3+ CD4- CD8- (double negative) T cells in patients with systemic lupus erythematosus: production of IL-4. Author(s): Dean GS, Anand A, Blofeld A, Isenberg DA, Lydyard PM. Source: Lupus. 2002; 11(8): 501-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220104&dopt=Abstract
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Characterization of flares in patients with systemic lupus erythematosus: comment on the article by Ho et al. Author(s): Ayoub N, Ayoub G, Rouphael N. Source: Arthritis and Rheumatism. 2003 February; 48(2): 581-2; Author Reply 582. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571875&dopt=Abstract
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Choroiditis in systemic lupus erythematosus: systemic steroid therapy and focal laser treatment. Author(s): Shimura M, Tatehana Y, Yasuda K, Saito S, Sasaki T, Tamai M. Source: Japanese Journal of Ophthalmology. 2003 May-June; 47(3): 312-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782171&dopt=Abstract
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Chronic lupus peritonitis with massive ascites at elderly onset: case report and review of the literature. Author(s): Ito H, Nanamiya W, Kuroda N, Inoue M, Sasaoka A, Chijiwa T, Nishiya K, Hashimoto K, Nakagawa O. Source: Intern Med. 2002 November; 41(11): 1056-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487191&dopt=Abstract
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Chronic monoarthritis of the knee in systemic lupus erythematosus. Author(s): Wong RC, Kong KO, Lin RV, Barkham T. Source: Lupus. 2003; 12(4): 324-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729059&dopt=Abstract
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Cigarette smoking and disease activity in systemic lupus erythematosus. Author(s): Ghaussy NO, Sibbitt W Jr, Bankhurst AD, Qualls CR. Source: The Journal of Rheumatology. 2003 June; 30(6): 1215-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784392&dopt=Abstract
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Class V lupus nephritis: a clinicopathologic study in 152 patients. Author(s): Chen Q, Liu Z, Hu W, Chen H, Zeng C, Li L. Source: Journal of Nephrology. 2003 January-February; 16(1): 126-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653107&dopt=Abstract
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Clinical and serological associations of ribosomal P autoantibodies in systemic lupus erythematosus: prospective evaluation in a large cohort of Italian patients. Author(s): Gerli R, Caponi L, Tincani A, Scorza R, Sabbadini MG, Danieli MG, De Angelis V, Cesarotti M, Piccirilli M, Quartesan R, Moretti P, Cantoni C, Franceschini F, Cavazzana I, Origgi L, Vanoli M, Bozzolo E, Ferrario L, Padovani A, Gambini O, Vanzulli L, Croce D, Bombardieri S. Source: Rheumatology (Oxford, England). 2002 December; 41(12): 1357-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468814&dopt=Abstract
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Clinical image: a hungry histiocyte: lupus-related hemophagocytic syndrome. Author(s): Lloyd MS, Bethel KJ, Pischel KD. Source: Arthritis and Rheumatism. 2002 September; 46(9): 2537. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355503&dopt=Abstract
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Clinical outcomes of patients with biopsy-proven lupus nephritis in NUH. Author(s): Gan HC, Hyoon K, Fong KY. Source: Singapore Med J. 2002 December; 43(12): 614-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693764&dopt=Abstract
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Clinical presentations and vascular histopathology in autopsied patients with systemic lupus erythematosus and anticardiolipin antibodies. Author(s): Sipek-Dolnicar A, Hojnik M, Bozic B, Vizjak A, Rozman B, Ferluga D. Source: Clin Exp Rheumatol. 2002 May-June; 20(3): 335-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102469&dopt=Abstract
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Clinical relevance of peripheral vascular occlusive disease in patients with rheumatoid arthritis and systemic lupus erythematosus. Author(s): Henke PK, Sukheepod P, Proctor MC, Upchurch GR Jr, Stanley JC. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 July; 38(1): 111-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12844099&dopt=Abstract
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Clinical significance of acquired activated protein C resistance in patients with systemic lupus erythematosus. Author(s): Munoz-Rodriguez FJ, Reverter JC, Font J, Tassies D, Espinosa G, Cervera R, Carmona F, Balsch J, Ingelmo M, Ordinas A. Source: Lupus. 2002; 11(11): 730-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475003&dopt=Abstract
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CO2 laser vaporization for disfiguring lupus pernio. Author(s): Young HS, Chalmers RJ, Griffiths CE, August PJ. Source: Journal of Cosmetic and Laser Therapy : Official Publication of the European Society for Laser Dermatology. 2002 December; 4(3-4): 87-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623554&dopt=Abstract
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Coexistence of osteopoikilosis and discoid lupus erythematosus: a case report. Author(s): Bicer A, Tursen U, Ozer C, Kaya TI, Dusmez D, Ikizoglu G. Source: Clinical Rheumatology. 2002 September; 21(5): 405-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223992&dopt=Abstract
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Coexistence of pemphigus herpetiformis and systemic lupus erythematosus. Author(s): Marinovic B, Basta-Juzbasic A, Bukvic-Mokos Z, Leovic R, Loncaric D. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 May; 17(3): 316-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702075&dopt=Abstract
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Cognitive impairment in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus: a population-based neuropsychological study. Author(s): Loukkola J, Laine M, Ainiala H, Peltola J, Metsanoja R, Auvinen A, Hietaharju A. Source: J Clin Exp Neuropsychol. 2003 February; 25(1): 145-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607179&dopt=Abstract
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Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Author(s): Illei GG, Austin HA, Crane M, Collins L, Gourley MF, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Steinberg AD, Klippel JH, Balow JE, Boumpas DT. Source: Annals of Internal Medicine. 2001 August 21; 135(4): 248-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11511139&dopt=Abstract
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Comment on steroid hormones and disease activity during pregnancy in systemic lupus erythematosus. Author(s): Blumenfeld Z. Source: Arthritis and Rheumatism. 2002 December 15; 47(6): 691-2; Author Reply 692. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522846&dopt=Abstract
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Comparison of renal disease severity and outcome in patients with primary antiphospholipid syndrome, antiphospholipid syndrome secondary to systemic lupus erythematosus (SLE) and SLE alone. Author(s): Moss KE, Isenberg DA. Source: Rheumatology (Oxford, England). 2001 August; 40(8): 863-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11511754&dopt=Abstract
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Comparison of treatment regimes for lupus nephritis. Author(s): Yeap SS, Asarudin SI, Chow SK, Chua CT, Lai LC. Source: Med J Malaysia. 2002 September; 57(3): 311-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440271&dopt=Abstract
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Complex partial status epilepticus of extratemporal origin in a patient with systemic lupus erythematosus. Author(s): Fernandez-Torre JL, Sanchez JM, Gonzalez C, Fernandez-Guinea O. Source: Seizure : the Journal of the British Epilepsy Association. 2003 June; 12(4): 245-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12763474&dopt=Abstract
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Concomitant Cushing's syndrome due to adrenal adenoma in a patient with systemic lupus erythematosus. Author(s): Shimizu M, Kawata M, Okada T, Yuu H, Kurahashi T, Yamanaka K, Umezu K. Source: Intern Med. 2002 November; 41(11): 1044-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487188&dopt=Abstract
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Contraceptive practices in women with systemic lupus erythematosus and/or antiphospholipid syndrome: what advice should we be giving? Author(s): Lakasing L, Khamashta M. Source: The Journal of Family Planning and Reproductive Health Care / Faculty of Family Planning & Reproductive Health Care, Royal College of Obstetricians & Gynaecologists. 2001 January; 27(1): 7-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457539&dopt=Abstract
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Contribution of the initial features of systemic lupus erythematosus to the clinical evolution and survival of a cohort of Mediterranean patients. Author(s): Bujan S, Ordi-Ros J, Paredes J, Mauri M, Matas L, Cortes J, Vilardell M. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 859-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922959&dopt=Abstract
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Controversies and advances in the management of systemic lupus erythematosus in children and adolescents. Author(s): Tucker LB. Source: Best Practice & Research. Clinical Rheumatology. 2002 July; 16(3): 471-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387811&dopt=Abstract
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Coronary artery bypass grafting in patients with systemic lupus erythematosus. Author(s): Bossert T, Falk V, Gummert JF, Rahmel A, Mohr FW. Source: Zeitschrift Fur Kardiologie. 2003 March; 92(3): 219-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658468&dopt=Abstract
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Correlation between anti-Ro/La titers and clinical findings of patients with systemic lupus erythematosus. Author(s): Chien JW, Lin CY, Yang LY. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2001 May; 64(5): 283-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499338&dopt=Abstract
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Correlation between circulating CD27high plasma cells and disease activity in patients with systemic lupus erythematosus. Author(s): Jacobi AM, Odendahl M, Reiter K, Bruns A, Burmester GR, Radbruch A, Valet G, Lipsky PE, Dorner T. Source: Arthritis and Rheumatism. 2003 May; 48(5): 1332-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746906&dopt=Abstract
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Correlations of anti-dsDNA and anti-ribosomal P autoantibodies with lupus nephritis. Author(s): Reichlin M, Wolfson-Reichlin M. Source: Clinical Immunology (Orlando, Fla.). 2003 July; 108(1): 69-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865073&dopt=Abstract
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Cross-reactivity and pathogenicity of anti-DNA autoantibodies in systemic lupus erythematosus. Author(s): Mageed RA, Zack DJ. Source: Lupus. 2002; 11(12): 783-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529040&dopt=Abstract
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Cross-reactivity between anti-cardiolipin, anti-high-density lipoprotein and antiapolipoprotein A-I IgG antibodies in patients with systemic lupus erythematosus and primary antiphospholipid syndrome. Author(s): Delgado Alves J, Kumar S, Isenberg DA. Source: Rheumatology (Oxford, England). 2003 July; 42(7): 893-9. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730551&dopt=Abstract
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Cryptococcal meningitis in pediatric systemic lupus erythematosus. Author(s): Liou J, Chiu C, Tseng C, Chi C, Fu L. Source: Mycoses. 2003 April; 46(3-4): 153-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870207&dopt=Abstract
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CTLA-4 gene polymorphisms in systemic lupus erythematosus: a highly significant association with a determinant in the promoter region. Author(s): Hudson LL, Rocca K, Song YW, Pandey JP. Source: Human Genetics. 2002 October; 111(4-5): 452-5. Epub 2002 August 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384790&dopt=Abstract
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Current concepts for the management of systemic lupus erythematosus in adults: a therapeutic challenge. Author(s): Ioannou Y, Isenberg DA. Source: Postgraduate Medical Journal. 2002 October; 78(924): 599-606. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415083&dopt=Abstract
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Cutaneous histoplasmosis in a patient with systemic lupus erythematosis. Author(s): Price DA, Ong EL. Source: The Lancet Infectious Diseases. 2003 May; 3(5): 296. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12726979&dopt=Abstract
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Cutaneous lupus erythematosus. Author(s): Perez Santos S, Garcia Morras P, Marengo Otero R, Gonzalez-Beato Merino MJ, Sanchez Herreros C. Source: Medicina Oral : Organo Oficial De La Sociedad Espanola De Medicina Oral Y De La Academia Iberoamericana De Patologia Y Medicina Bucal. 2001 March-April; 6(2): 151-2. English, Spanish. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11500632&dopt=Abstract
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Cutaneous Mycobacterium fortuitum infection mimicking lupus vulgaris. Author(s): Lin YC, Chiu HC, Hsiao CH, Jee SH, Liao YH. Source: The British Journal of Dermatology. 2002 July; 147(1): 170-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100204&dopt=Abstract
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Cutting edge: amelioration of kidney disease in a transgenic mouse model of lupus nephritis by administration of the caspase inhibitor carbobenzoxy-valyl-alanylaspartyl-(beta-o-methyl)-fluoromethylketone. Author(s): Seery JP, Cattell V, Watt FM. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 September 1; 167(5): 2452-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11509582&dopt=Abstract
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Cyclophosphamide therapy in a serious case of lupus nephritis during pregnancy. Author(s): Kart Koseoglu H, Yucel AE, Kunefeci G, Ozdemir FN, Duran H. Source: Lupus. 2001; 10(11): 818-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789493&dopt=Abstract
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Cytokine balance in kidney tissue from lupus nephritis patients. Author(s): Uhm WS, Na K, Song GW, Jung SS, Lee T, Park MH, Yoo DH. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 935-8. Epub 2003 March 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730502&dopt=Abstract
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Cytomegalovirus colitis following immunosuppressive therapy for lupus peritonitis and lupus nephritis. Author(s): Ohashi N, Isozaki T, Shirakawa K, Ikegaya N, Yamamoto T, Hishida A. Source: Intern Med. 2003 April; 42(4): 362-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729328&dopt=Abstract
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Daily psychosocial stressors and cyclic response patterns in urine cortisol and neopterin in a patient with systemic lupus erythematosus. Author(s): Schubert C, Lampe A, Geser W, Noisternig B, Fuchs D, Konig P, Chamson E, Schussler G. Source: Psychoneuroendocrinology. 2003 April; 28(3): 459-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573308&dopt=Abstract
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Decreased IL-12 production by polymorphonuclear leukocytes in patients with active systemic lupus erythematosus. Author(s): Tsai CY, Wu TH, Yu CL, Tsai YY, Chou CT. Source: Immunological Investigations. 2002 August-November; 31(3-4): 177-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472178&dopt=Abstract
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Decreased IL-4 producing CD4+ T cells in patients with active systemic lupus erythematosus-relation to IL-12R expression. Author(s): Sugimoto K, Morimoto S, Kaneko H, Nozawa K, Tokano Y, Takasaki Y, Hashimoto H. Source: Autoimmunity. 2002 September; 35(6): 381-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568118&dopt=Abstract
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Defective activity of ERK-1 and ERK-2 mitogen-activated protein kinases in peripheral blood T lymphocytes from patients with systemic lupus erythematosus: potential role of altered coupling of Ras guanine nucleotide exchange factor hSos to adapter protein Grb2 in lupus T cells. Author(s): Cedeno S, Cifarelli DF, Blasini AM, Paris M, Placeres F, Alonso G, Rodriguez MA. Source: Clinical Immunology (Orlando, Fla.). 2003 January; 106(1): 41-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584050&dopt=Abstract
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Defective expression and tyrosine phosphorylation of the T cell receptor zeta chain in peripheral blood T cells from systemic lupus erythematosus patients. Author(s): Pang M, Setoyama Y, Tsuzaka K, Yoshimoto K, Amano K, Abe T, Takeuchi T. Source: Clinical and Experimental Immunology. 2002 July; 129(1): 160-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100036&dopt=Abstract
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Defective production of functional 98-kDa form of Elf-1 is responsible for the decreased expression of TCR zeta-chain in patients with systemic lupus erythematosus. Author(s): Juang YT, Tenbrock K, Nambiar MP, Gourley MF, Tsokos GC. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 November 15; 169(10): 6048-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421992&dopt=Abstract
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Defenses gone awry. Lupus. Author(s): Litton K. Source: Rn. 2003 March; 66(3): 53-9; Quiz 60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12677880&dopt=Abstract
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Deficient protein kinase a in systemic lupus erythematosus: a disorder of T lymphocyte signal transduction. Author(s): Kammer GM. Source: Annals of the New York Academy of Sciences. 2002 June; 968: 96-105. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119270&dopt=Abstract
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Defining lupus cases for clinical studies: the Boston weighted criteria for the classification of systemic lupus erythematosus. Author(s): Costenbader KH, Karlson EW, Mandl LA. Source: The Journal of Rheumatology. 2002 December; 29(12): 2545-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465149&dopt=Abstract
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Definition of risk factors for death, end stage renal disease, and thromboembolic events in a monocentric cohort of 338 patients with systemic lupus erythematosus. Author(s): Manger K, Manger B, Repp R, Geisselbrecht M, Geiger A, Pfahlberg A, Harrer T, Kalden JR. Source: Annals of the Rheumatic Diseases. 2002 December; 61(12): 1065-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429536&dopt=Abstract
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Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Author(s): Chang DM, Lan JL, Lin HY, Luo SF. Source: Arthritis and Rheumatism. 2002 November; 46(11): 2924-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428233&dopt=Abstract
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Dehydroepiandrosterone, a sex steroid metabolite in development for systemic lupus erythematosus. Author(s): Merrill JT. Source: Expert Opinion on Investigational Drugs. 2003 June; 12(6): 1017-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783605&dopt=Abstract
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Delayed lupus onset in (NZB x NZW)F1 mice expressing a human C-reactive protein transgene. Author(s): Szalai AJ, Weaver CT, McCrory MA, van Ginkel FW, Reiman RM, Kearney JF, Marion TN, Volanakis JE. Source: Arthritis and Rheumatism. 2003 June; 48(6): 1602-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794828&dopt=Abstract
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Delineation of the pathogenesis of systemic lupus erythematosus by using murine models. Author(s): Liu K, Wakeland EK. Source: Advances in Experimental Medicine and Biology. 2001; 490: 1-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11505967&dopt=Abstract
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Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus. Author(s): Lu Q, Kaplan M, Ray D, Ray D, Zacharek S, Gutsch D, Richardson B. Source: Arthritis and Rheumatism. 2002 May; 46(5): 1282-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115234&dopt=Abstract
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Demographic differences in the development of lupus nephritis: a retrospective analysis. Author(s): Seligman VA, Lum RF, Olson JL, Li H, Criswell LA. Source: The American Journal of Medicine. 2002 June 15; 112(9): 726-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12079714&dopt=Abstract
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Demonstration of necrotizing fasciitis on Ga-67 scans in a patient with systemic lupus erythematosus. Author(s): Hung GU, Lan JL, Lin WY, Wang SJ. Source: Clinical Nuclear Medicine. 2003 February; 28(2): 160. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544146&dopt=Abstract
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Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis. Author(s): Grootscholten C, van Bruggen MC, van der Pijl JW, de Jong EM, Ligtenberg G, Derksen RH, Berden JH; Dutch Working Party on Systemic Lupus Erythematosus. Source: Arthritis and Rheumatism. 2003 May; 48(5): 1355-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746908&dopt=Abstract
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Dermatomyositis relapse complicated with gastric carcinoma and lupus nephritis five years after the initial diagnosis of dermatomyositis. Author(s): Nakaya I, Iwata Y, Sugiyama Y, Abe T, Nomura G. Source: Intern Med. 2002 June; 41(6): 502-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135189&dopt=Abstract
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Design, quality, and bias in randomized controlled trials of systemic lupus erythematosus. Author(s): Karassa FB, Tatsioni A, Ioannidis JP. Source: The Journal of Rheumatology. 2003 May; 30(5): 979-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734892&dopt=Abstract
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Detection and clinical significance of Ba2+- and Sr2+-dependent antiprothrombin antibodies in patients with systemic lupus erythematosus and antiphospholipid syndrome. Author(s): Sanaka T, Matsuda J, Teramoto T. Source: Lupus. 2003; 12(2): 117-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630756&dopt=Abstract
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Detection of anti-elongation factor 2 kinase (calmodulin-dependent protein kinase III) antibodies in patients with systemic lupus erythematosus. Author(s): Arora S, Yang JM, Craft J, Hait W. Source: Biochemical and Biophysical Research Communications. 2002 May 10; 293(3): 1073-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051769&dopt=Abstract
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Detection of lupus anticoagulant identifies patients with autoimmune haemolytic anaemia at increased risk for venous thromboembolism. Author(s): Pullarkat V, Ngo M, Iqbal S, Espina B, Liebman HA. Source: British Journal of Haematology. 2002 September; 118(4): 1166-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199802&dopt=Abstract
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Development and assessment of a World Wide Web site for systemic lupus erythematosus patient information. Author(s): Young SP, Henderson E, Cheseldine DL, Wilson AS, Skan J, Heaton S, Bowman SJ, Situnayake D, Bacon PA, Southwood TR, Gordon C. Source: Lupus. 2002; 11(8): 478-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220101&dopt=Abstract
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Development of an in vitro miniature model to simulate immunoadsorption in patients with systemic lupus erythematosus. Author(s): Avenhaus B, Avenhaus W, Schneider M, Domschke W, Gaubitz M. Source: Journal of Clinical Apheresis. 2002; 17(4): 183-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494411&dopt=Abstract
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Development of systemic lupus erythematosus in a patient with congenital heart block. Author(s): Feist E, Keitzer R, Gerhold K, Horvath L, Wahren-Herlenius M, Dorner T. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2697-8; Discussion 2699. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130495&dopt=Abstract
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Development of systemic lupus erythematosus in a young child affected with chronic granulomatous disease following withdrawal of treatment with interferon-gamma. Author(s): Badolato R, Notarangelo LD, Plebani A, Roos D. Source: Rheumatology (Oxford, England). 2003 June; 42(6): 804-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771442&dopt=Abstract
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Dextran sulfate (Selesorb) plasma apheresis improves vascular changes in systemic lupus erythematosus. Author(s): Braun N, Junger M, Klein R, Gutenberger S, Guagnin M, Risler T. Source: Therapeutic Apheresis : Official Journal of the International Society for Apheresis and the Japanese Society for Apheresis. 2002 December; 6(6): 471-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460414&dopt=Abstract
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Diagnosis and management of lupus pleuritis. Author(s): Wang DY. Source: Current Opinion in Pulmonary Medicine. 2002 July; 8(4): 312-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055395&dopt=Abstract
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Diagnosis and management of patients with neuropsychiatric systemic lupus erythematosus (NPSLE). Author(s): Hermosillo-Romo D, Brey RL. Source: Best Practice & Research. Clinical Rheumatology. 2002 April; 16(2): 229-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041951&dopt=Abstract
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Diagnosis of lupus anticoagulant in the lupus anticoagulant-hypoprothrombinemia syndrome: report of two cases and review of the literature. Author(s): Baca V, Montiel G, Meillon L, Pizzuto J, Catalan T, Juan-Shum L, Nieva B. Source: American Journal of Hematology. 2002 November; 71(3): 200-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410576&dopt=Abstract
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Diagnosis of lupus: a glass half full. Author(s): Clough JD. Source: Cleve Clin J Med. 2002 February; 69(2): 141-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990643&dopt=Abstract
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Diet and systemic lupus erythematosus: a 4 year prospective study of Japanese patients. Author(s): Minami Y, Sasaki T, Arai Y, Kurisu Y, Hisamichi S. Source: The Journal of Rheumatology. 2003 April; 30(4): 747-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672194&dopt=Abstract
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Differences by race, sex and age in the clinical and immunologic features of recently diagnosed systemic lupus erythematosus patients in the southeastern United States. Author(s): Cooper GS, Parks CG, Treadwell EL, St Clair EW, Gilkeson GS, Cohen PL, Roubey RA, Dooley MA. Source: Lupus. 2002; 11(3): 161-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999880&dopt=Abstract
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Diffuse alveolar hemorrhage in systemic lupus erythematosus. Author(s): Zandman-Goddard G, Ehrenfeld M, Levy Y, Tal S. Source: Isr Med Assoc J. 2002 June; 4(6): 470. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12073430&dopt=Abstract
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Diffuse alveolar hemorrhage in systemic lupus erythematosus: a single center retrospective study in Taiwan. Author(s): Chang MY, Fang JT, Chen YC, Huang CC. Source: Renal Failure. 2002 November; 24(6): 791-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472201&dopt=Abstract
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Diffusion-weighted echo-planar MR imaging of CNS involvement in systemic lupus erythematosus. Author(s): Moritani T, Shrier DA, Numaguchi Y, Takahashi C, Yano T, Nakai K, Zhong J, Wang HZ, Shibata DK, Naselli SM. Source: Academic Radiology. 2001 August; 8(8): 741-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11508753&dopt=Abstract
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Dilute prothrombin time-based lupus ratio test. Integrated LA testing with recombinant tissue thromboplastin. Author(s): Liestol S, Jacobsen EM, Wisloff F. Source: Thrombosis Research. 2002 January 15; 105(2): 177-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958810&dopt=Abstract
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Direct transfer of p65 into T lymphocytes from systemic lupus erythematosus patients leads to increased levels of interleukin-2 promoter activity. Author(s): Herndon TM, Juang YT, Solomou EE, Rothwell SW, Gourley MF, Tsokos GC. Source: Clinical Immunology (Orlando, Fla.). 2002 May; 103(2): 145-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027419&dopt=Abstract
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Directing autoimmunity to nucleoprotein particles: the impact of dendritic cells and interferon alpha in lupus. Author(s): Hardin JA. Source: The Journal of Experimental Medicine. 2003 March 17; 197(6): 681-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642600&dopt=Abstract
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Discoid lupus erythematosus and cicatrizing conjunctivitis: clinicopathologic study of two cases. Author(s): Thorne JE, Jabs DA, Nikolskaia O, Anhalt G, Nousari HC. Source: Ocular Immunology and Inflammation. 2002 December; 10(4): 287-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854037&dopt=Abstract
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Discoid lupus erythematosus and lupus profundus in childhood: a report of two cases. Author(s): Wimmershoff MB, Hohenleutner U, Landthaler M. Source: Pediatric Dermatology. 2003 March-April; 20(2): 140-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657012&dopt=Abstract
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Discoid lupus erythematosus in children: clinical, histopathologic, and follow-up features in 27 cases. Author(s): Moises-Alfaro C, Berron-Perez R, Carrasco-Daza D, Gutierrez-Castrellon P, Ruiz-Maldonado R. Source: Pediatric Dermatology. 2003 March-April; 20(2): 103-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657003&dopt=Abstract
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Discoid lupus erythematosus presenting as madarosis. Author(s): Selva D, Chen CS, James CL, Huilgol SC. Source: American Journal of Ophthalmology. 2003 September; 136(3): 545-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967814&dopt=Abstract
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Disease activity and antinucleosome antibodies in systemic lupus erythematosus. Author(s): Benucci M, Gobbi FL, Del Rosso A, Cesaretti S, Niccoli L, Cantini F. Source: Scandinavian Journal of Rheumatology. 2003; 32(1): 42-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635945&dopt=Abstract
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Disseminated candidiasis following prednisolone therapy in systemic lupus erythematosus. Author(s): Tanaka H, Suzuki K, Nakahata T, Tateyama T, Sugimoto K, Ito E, Waga S. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 December; 44(6): 702-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421277&dopt=Abstract
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Divergence in intracellular signaling between interleukin-4 (IL-4) and IL-13 in human cells localizes to monomeric/dimeric expression of a transcription factor, the lupus autoantigen 70/80, induced by both cytokines. Author(s): Kelavkar U, Wang S, Badr K. Source: Advances in Experimental Medicine and Biology. 2002; 507: 483-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664629&dopt=Abstract
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DNA methylation in systemic lupus erythematosus. Author(s): Sekigawa I, Okada M, Ogasawara H, Kaneko H, Hishikawa T, Hashimoto H. Source: Lupus. 2003; 12(2): 79-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630750&dopt=Abstract
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DNASE I mutation and systemic lupus erythematosus in a Spanish population: comment on the article by Tew et al. Author(s): Balada E, Ordi-Ros J, Hernanz S, Villarreal J, Cortes F, Vilardell-Tarres M, Labrador M. Source: Arthritis and Rheumatism. 2002 July; 46(7): 1974-6; Author Reply 1976-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124889&dopt=Abstract
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Does Hermansky-Pudlak syndrome predispose to systemic lupus erythematosus? Author(s): Mitsui H, Komine M, Watanabe T, Kikuchi K, Okochi H, Tamaki K. Source: The British Journal of Dermatology. 2002 May; 146(5): 908-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12000395&dopt=Abstract
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Drug-induced lupus as a cause of relapsing inflammatory disease after renal transplantation. Author(s): Pape L, Strehlau J, Latta K, Ehrich JH, Offner G. Source: Pediatric Transplantation. 2002 August; 6(4): 337-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234276&dopt=Abstract
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Drug-induced lupus following treatment with infliximab in rheumatoid arthritis. Author(s): Favalli EG, Sinigaglia L, Varenna M, Arnoldi C. Source: Lupus. 2002; 11(11): 753-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475006&dopt=Abstract
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Drug-induced systemic lupus erythematosus and TNF-alpha blockers. Author(s): Mohan AK, Edwards ET, Cote TR, Siegel JN, Braun MM. Source: Lancet. 2002 August 24; 360(9333): 646. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12241965&dopt=Abstract
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Drug-induced systemic lupus erythematosus and TNF-alpha blockers. Author(s): Ferraccioli GF, Assaloni R, Perin A. Source: Lancet. 2002 August 24; 360(9333): 645; Author Reply 646. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12241963&dopt=Abstract
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Drug-induced systemic lupus erythematosus associated with etanercept therapy in a child with juvenile idiopathic arthritis. Author(s): Lepore L, Marchetti F, Facchini S, Leone V, Ventura A. Source: Clin Exp Rheumatol. 2003 March-April; 21(2): 276-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747299&dopt=Abstract
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Drug-induced, Ro/SSA-positive cutaneous lupus erythematosus. Author(s): Srivastava M, Rencic A, Diglio G, Santana H, Bonitz P, Watson R, Ha E, Anhalt GJ, Provost TT, Nousari CH. Source: Archives of Dermatology. 2003 January; 139(1): 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533163&dopt=Abstract
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Dysphagia in a patient with lupus and review of the literature. Author(s): Chua S, Dodd H, Saeed IT, Chakravarty K. Source: Lupus. 2002; 11(5): 322-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090569&dopt=Abstract
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Dysphagia in patients with systemic lupus erythematosus. Author(s): Jimenez-Alonso J, Estev D, Vera C, Sabio JM; Grupo Lupus Virgen de las Nieves. Source: Lupus. 2003; 12(6): 493. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873055&dopt=Abstract
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Dysregulation of the granulocyte-macrophage colony-stimulating factor receptor is one of the causes of defective expression of CD80 antigen in systemic lupus erythematosus. Author(s): Funauchi M, Yoo BS, Nozaki Y, Sugiyama M, Ohno M, Kinoshita K, Kanamaru A. Source: Lupus. 2002; 11(5): 317-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090568&dopt=Abstract
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Ear involvement in systemic lupus erythematosus patients: a comparative study. Author(s): Kastanioudakis I, Ziavra N, Voulgari PV, Exarchakos G, Skevas A, Drosos AA. Source: The Journal of Laryngology and Otology. 2002 February; 116(2): 103-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11827581&dopt=Abstract
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Ear involvement in systemic lupus erythematosus patients: a comparative study. J Laryngol Otol 116:103-7. Author(s): Jimenez-Alonson J, Gutierrez-Cabello F, Castillo JL, Sabio JM, HidalgoTenorio C, Leon L; Grupo Lupus Virgen de las Nieves. Source: The Journal of Laryngology and Otology. 2002 September; 116(9): 746. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437818&dopt=Abstract
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Early diagnosis and monitoring of active HCMV infection in children with systemic lupus erythematosus. Author(s): Zhang C, Shen K, Jiang Z, He X. Source: Chin Med J (Engl). 2001 December; 114(12): 1309-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11793860&dopt=Abstract
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EBER-1 positive diffuse large cell lymphoma presenting as lupus nephritis. Author(s): Lin MH, Huang JJ, Chen TY, Chen FF, Chang KC, Liu MF, Huang WT, Su WC, Tsao CJ. Source: Lupus. 2003; 12(6): 486-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873053&dopt=Abstract
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Echocardiographic abnormalities and antiphospholipid antibodies in patients with systemic lupus erythematosus. Author(s): Falcao CA, Alves IC, Chahade WH, Duarte AL, Lucena-Silva N. Source: Arquivos Brasileiros De Cardiologia. 2002 September; 79(3): 285-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386730&dopt=Abstract
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Effect of a diet program on lipid and lipoproteins, body weight, nutrient intakes, and quality of life in patients with systemic lupus erythematosus. Author(s): Borba EF, Bonfa E. Source: The Journal of Rheumatology. 2003 June; 30(6): 1393-4; Author Reply 1394. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784425&dopt=Abstract
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Effect of environmental changes on oxidative deoxyribonucleic acid (DNA) damage in systemic lupus erythematosus. Author(s): Maeshima E, Liang XM, Otani H, Mune M, Yukawa S. Source: Archives of Environmental Health. 2002 September-October; 57(5): 425-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641184&dopt=Abstract
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Effect of murine recombinant IL-2 on the course of lupus-like disease in (NZBxNZW) F1 female mice. Author(s): Ravel G, Christ M, Ruat C, Burnett R, Descotes J. Source: Immunopharmacology and Immunotoxicology. 2002 August; 24(3): 409-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375737&dopt=Abstract
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Effect of selective posterior rhizotomy on transverse myelitis in a patient with systemic lupus erythematosus. Author(s): Yang TF, Lee SS, Lin PH, Chen H, Chan RC. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2002 June; 81(6): 467-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023605&dopt=Abstract
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Effect of sera from women with systemic lupus erythematosus or antiphospholipid syndrome and recurrent abortions on human placental explants in culture. Author(s): Yacobi S, Ornoy A, Blumenfeld Z, Miller RK. Source: Teratology. 2002 December; 66(6): 300-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486763&dopt=Abstract
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Effect of trichostatin A on human T cells resembles signaling abnormalities in T cells of patients with systemic lupus erythematosus: a new mechanism for TCR zeta chain deficiency and abnormal signaling. Author(s): Nambiar MP, Warke VG, Fisher CU, Tsokos GC. Source: Journal of Cellular Biochemistry. 2002; 85(3): 459-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11967985&dopt=Abstract
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Effects of a self-management course for patients with systemic lupus erythematosus. Author(s): Sohng KY. Source: Journal of Advanced Nursing. 2003 June; 42(5): 479-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752868&dopt=Abstract
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Effects of liposteroid on the hemophagocytic syndrome in systemic lupus erythematosus. Author(s): Funauchi M, Ohno M, Yamagata T, Nozaki Y, Kinoshita K, Kanamaru A. Source: Lupus. 2003; 12(6): 483-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873052&dopt=Abstract
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Effects of prasterone on corticosteroid requirements of women with systemic lupus erythematosus: a double-blind, randomized, placebo-controlled trial. Author(s): Petri MA, Lahita RG, Van Vollenhoven RF, Merrill JT, Schiff M, Ginzler EM, Strand V, Kunz A, Gorelick KJ, Schwartz KE; GL601 Study Group. Source: Arthritis and Rheumatism. 2002 July; 46(7): 1820-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124866&dopt=Abstract
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Effects of stress on serum prolactin levels in patients with systemic lupus erythematosus. Author(s): Dostal C, Marek J, Moszkorzova L, Lacinova Z, Musilova L, Zvarova J. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 247-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114279&dopt=Abstract
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Efficacy of isoniazid prophylaxis in patients with systemic lupus erythematosus receiving long term steroid treatment. Author(s): Gaitonde S, Pathan E, Sule A, Mittal G, Joshi VR. Source: Annals of the Rheumatic Diseases. 2002 March; 61(3): 251-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11830432&dopt=Abstract
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Efficacy of IVIG affinity-purified anti-double-stranded DNA anti-idiotypic antibodies in the treatment of an experimental murine model of systemic lupus erythematosus. Author(s): Shoenfeld Y, Rauova L, Gilburd B, Kvapil F, Goldberg I, Kopolovic J, Rovensky J, Blank M. Source: International Immunology. 2002 November; 14(11): 1303-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407021&dopt=Abstract
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Efficacy of low-dose versus high-dose cyclophosphamide in lupus nephritis: comment on the article by Houssiau et al. Author(s): Block JA. Source: Arthritis and Rheumatism. 2003 May; 48(5): 1466; Author Reply 1466-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746929&dopt=Abstract
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Efficacy of topical tacrolimus for treating the malar rash of systemic lupus erythematosus. Author(s): Kanekura T, Yoshii N, Terasaki K, Miyoshi H, Kanzaki T. Source: The British Journal of Dermatology. 2003 February; 148(2): 353-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12588393&dopt=Abstract
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Elevated blood viscosity in systemic lupus erythematosus. Author(s): Rosenson RS, Shott S, Katz R. Source: Seminars in Arthritis and Rheumatism. 2001 August; 31(1): 52-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11503139&dopt=Abstract
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Elevated homocysteine levels in patients with Raynaud's phenomenon secondary to systemic lupus erythematosus. Author(s): Cheng TT, Chiu CK. Source: Clinical Rheumatology. 2002 June; 21(3): 251-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111632&dopt=Abstract
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Elevated IL-16 levels in patients with systemic lupus erythematosus are associated with disease severity but not with genetic susceptibility to lupus. Author(s): Lard LR, Roep BO, Verburgh CA, Zwinderman AH, Huizinga TW. Source: Lupus. 2002; 11(3): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999883&dopt=Abstract
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Elevated plasma concentrations of nitric oxide, soluble thrombomodulin and soluble vascular cell adhesion molecule-1 in patients with systemic lupus erythematosus. Author(s): Ho CY, Wong CK, Li EK, Tam LS, Lam CW. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509624&dopt=Abstract
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Elevated production of interleukin-18 is associated with renal disease in patients with systemic lupus erythematosus. Author(s): Wong CK, Ho CY, Li EK, Tam LS, Lam CW. Source: Clinical and Experimental Immunology. 2002 November; 130(2): 345-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390326&dopt=Abstract
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Elevated triglycerides and low levels of high-density lipoprotein as markers of disease activity in association with up-regulation of the tumor necrosis factor alpha/tumor necrosis factor receptor system in systemic lupus erythematosus. Author(s): Svenungsson E, Gunnarsson I, Fei GZ, Lundberg IE, Klareskog L, Frostegard J. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2533-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130473&dopt=Abstract
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Emerging concepts in the molecular pathogenesis of systemic lupus erythematosus. Author(s): Nambiar MP, Juang YT, Tsokos GC. Source: Arch Immunol Ther Exp (Warsz). 2002; 50(1): 35-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916307&dopt=Abstract
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Endogenous retroviruses in systemic lupus erythematosus: candidate lupus viruses. Author(s): Adelman MK, Marchalonis JJ. Source: Clinical Immunology (Orlando, Fla.). 2002 February; 102(2): 107-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846452&dopt=Abstract
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Endothelial cell binding by systemic lupus antibodies: functional properties and relationship with anti-DNA activity. Author(s): Moscato S, Pratesi F, Bongiorni F, Scavuzzo MC, Chimenti D, Bombardieri S, Migliorini P. Source: Journal of Autoimmunity. 2002 May; 18(3): 231-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126636&dopt=Abstract
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Engagement of complement receptor 2 on the surface of B cells from patients with systemic lupus erythematosus contributes to the increased responsiveness to antigen stimulation. Author(s): Mitchell JP, Enyedy EJ, Nambiar MP, Lees A, Tsokos GC. Source: Lupus. 2002; 11(5): 299-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090564&dopt=Abstract
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Enhancement of T cell apoptosis correlates with increased serum levels of soluble Fas (CD95/Apo-1) in active lupus. Author(s): Silvestris F, Grinello D, Tucci M, Cafforio P, Dammacco F. Source: Lupus. 2003; 12(1): 8-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587820&dopt=Abstract
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Epidemiology of systemic lupus erythematosus in northwest Greece 1982-2001. Author(s): Alamanos Y, Voulgari PV, Siozos C, Katsimpri P, Tsintzos S, Dimou G, Politi EN, Rapti A, Laina G, Drosos AA. Source: The Journal of Rheumatology. 2003 April; 30(4): 731-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672191&dopt=Abstract
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Epidemiology of systemic lupus erythematosus. Author(s): Petri M. Source: Best Practice & Research. Clinical Rheumatology. 2002 December; 16(5): 847-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12473278&dopt=Abstract
154 Lupus
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Epidermodysplasia verruciformis-like lesions in a patient with systemic lupus erythematosus. Author(s): Garcia-Rio I, Garcia-F-Villalta MJ, Dauden E, Fraga J, Garcia-Diez A. Source: Acta Dermato-Venereologica. 2003; 83(3): 229-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816165&dopt=Abstract
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Epilepsy associated with lupus anticoagulant. Author(s): Gibbs JW 3rd, Husain AM. Source: Seizure : the Journal of the British Epilepsy Association. 2002 April; 11(3): 207-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018967&dopt=Abstract
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Epitope spreading in systemic lupus erythematosus: comment on the article by Monneaux and Muller. Author(s): Hoffman RW, Greidinger EL. Source: Arthritis and Rheumatism. 2003 February; 48(2): 582-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571876&dopt=Abstract
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Epitope spreading in systemic lupus erythematosus: identification of triggering peptide sequences. Author(s): Monneaux F, Muller S. Source: Arthritis and Rheumatism. 2002 June; 46(6): 1430-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115171&dopt=Abstract
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Epstein-barr virus-associated non-Hodgkin's lymphoma of B-cell origin, Hodgkin's disease, acute leukemia, and systemic lupus erythematosus: a serologic and molecular analysis. Author(s): Mitarnun W, Pradutkanchana J, Takao S, Saechan V, Suwiwat S, Ishida T. Source: J Med Assoc Thai. 2002 May; 85(5): 552-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188384&dopt=Abstract
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Estimating the incidence of systemic lupus erythematosus in a tropical region (Natal, Brazil). Author(s): Vilar MJ, Sato EI. Source: Lupus. 2002; 11(8): 528-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220107&dopt=Abstract
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Estimation of anticardiolipin antibodies, anti-beta2 glycoprotein I antibodies and lupus anticoagulant in a prospective longitudinal study of children with juvenile idiopathic arthritis. Author(s): Avcin T, Ambrozic A, Bozic B, Accetto M, Kveder T, Rozman' B. Source: Clin Exp Rheumatol. 2002 January-February; 20(1): 101-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892692&dopt=Abstract
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Etanercept-induced lupus-like syndrome in a patient with rheumatoid arthritis. Author(s): Carlson E, Rothfield N. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1165-6; Author Reply 1166. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687569&dopt=Abstract
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European Consensus Lupus Activity Measurement is sensitive to change in disease activity in childhood-onset systemic lupus erythematosus. Author(s): Brunner HI, Silverman ED, Bombardier C, Feldman BM. Source: Arthritis and Rheumatism. 2003 June 15; 49(3): 335-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794788&dopt=Abstract
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Evaluation of antigen-based heteropolymer for treatment of systemic lupus erythematosus in a nonhuman primate model. Author(s): Pincus SE, Lukacher N, Mohamed N, Sesay M, Zabinski R, Ebelle R, Duncan L, Li J, Chen X, Peng W, Adaelu J, Casey L, Porter JP, Spitalny G, Nardone LL. Source: Clinical Immunology (Orlando, Fla.). 2002 November; 105(2): 141-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482388&dopt=Abstract
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Evaluation of lipid profile, macular toxicity and clinical manifestations according to APO E genotype in systemic lupus erythematosus and rheumatoid arthritis patients treated with chloroquine. Author(s): Vazquez-Del MM, Munoz-Valle JF, Santos A, Bernard-Medina AG, MartinezBonilla G, Paczka JA, Ruiz-Garcia H, Orozco-Alcala J, Orozco-Barocio G, QuezadaArellano D, Gurrola-Diaz C, Nuno-Gonzalez P, Best-Aguilera CR, Chavez-Castellanos R, Panduro A. Source: Scandinavian Journal of Rheumatology. 2002; 31(1): 32-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11922198&dopt=Abstract
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Evaluation of the capacity of sunscreens to photoprotect lupus erythematosus patients by employing the photoprovocation test. Author(s): Stege H, Budde MA, Grether-Beck S, Richard A, Rougier A, Krutmann J. Source: Eur J Dermatol. 2002 July-August; 12(4): Vii-Ix. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12118427&dopt=Abstract
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Evidence for a susceptibility gene (SLEH1) on chromosome 11q14 for systemic lupus erythematosus (SLE) families with hemolytic anemia. Author(s): Kelly JA, Thompson K, Kilpatrick J, Lam T, Nath SK, Gray-McGuire C, Reid J, Namjou B, Aston CE, Bruner GR, Scofield RH, Harley JB. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 September 3; 99(18): 11766-71. Epub 2002 August 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192084&dopt=Abstract
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Evidence for aerobic insufficiency in women with systemic Lupus erythematosus. Author(s): Keyser RE, Rus V, Cade WT, Kalappa N, Flores RH, Handwerger BS. Source: Arthritis and Rheumatism. 2003 February 15; 49(1): 16-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579589&dopt=Abstract
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Exacerbation of extrarenal systemic lupus erythematosus following peritonitis in peritoneal dialysis. Author(s): Servilla KS, Tzamaloukas AH. Source: Perit Dial Int. 2003 January-February; 23(1): 96-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691519&dopt=Abstract
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Existence of IgA-antiprothrombin antibody in a patient with systemic lupus erythematosus. Author(s): Matsuda J, Sanaka T, Yoshida M, Gotoh M, Gohchi K. Source: European Journal of Haematology. 2002 August; 69(2): 126-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366720&dopt=Abstract
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Exposure of anionic phospholipids serves as anti-inflammatory and immunosuppressive signal--implications for antiphospholipid syndrome and systemic lupus erythematosus. Author(s): Gaipl US, Beyer TD, Baumann I, Voll RE, Stach CM, Heyder P, Kalden JR, Manfredi A, Herrmann M. Source: Immunobiology. 2003; 207(1): 73-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638907&dopt=Abstract
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Expression of cyclin B1 and cyclin dependent kinase inhibitor p21 in lymphocytes in patients with systemic lupus erythematosus. Author(s): Ho CY, Wong CK, Li EK, Tam LS, Lam CW. Source: The Journal of Rheumatology. 2002 December; 29(12): 2537-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465148&dopt=Abstract
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Expression of cytokine- and chemokine-related genes in peripheral blood mononuclear cells from lupus patients by cDNA array. Author(s): Rus V, Atamas SP, Shustova V, Luzina IG, Selaru F, Magder LS, Via CS. Source: Clinical Immunology (Orlando, Fla.). 2002 March; 102(3): 283-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890715&dopt=Abstract
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Expression of interleukin-12 and its signaling molecules in peripheral blood mononuclear cells in systemic lupus erythematosus patients. Author(s): Li Z, Li Y, Huang L, Xu H, Yu X, Ye R. Source: Chin Med J (Engl). 2002 June; 115(6): 846-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12123550&dopt=Abstract
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Expression of recombination activating genes 1 and 2 in peripheral B cells of patients with systemic lupus erythematosus. Author(s): Girschick HJ, Grammer AC, Nanki T, Vazquez E, Lipsky PE. Source: Arthritis and Rheumatism. 2002 May; 46(5): 1255-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115231&dopt=Abstract
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Expression of the markers BDCA-2 and BDCA-4 and production of interferon-alpha by plasmacytoid dendritic cells in systemic lupus erythematosus. Author(s): Blomberg S, Eloranta ML, Magnusson M, Alm GV, Ronnblom L. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2524-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130472&dopt=Abstract
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Extensive calcinosis cutis in association with systemic lupus erythematosus. Author(s): Bhatia S, Silverberg NB, Don PC, Weinberg JM. Source: Acta Dermato-Venereologica. 2001 November-December; 81(6): 446-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859960&dopt=Abstract
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Extra hepatic portal vein thrombosis in a child associated with lupus anticoagulant. Author(s): Pati HP, Srivastava A, Sahni P. Source: Journal of Tropical Pediatrics. 2003 June; 49(3): 191-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848215&dopt=Abstract
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Extracorporeal membrane oxygenation in fulminant myocarditis complicating systemic lupus erythematosus. Author(s): Leung MC, Harper RW, Boxall J. Source: The Medical Journal of Australia. 2002 April 15; 176(8): 374-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041632&dopt=Abstract
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Extrapontine myelinolysis in a patient with systemic lupus erythematosus: a case report. Author(s): Tsai MH, Lu CS, Chen CJ, Tsai WP, Liou LB. Source: J Formos Med Assoc. 2002 July; 101(7): 505-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353344&dopt=Abstract
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Extravascular necrotizing palisaded granulomas as the presenting skin sign of systemic lupus erythematosus. Author(s): Obermoser G, Zelger B, Zangerle R, Sepp N. Source: The British Journal of Dermatology. 2002 August; 147(2): 371-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174116&dopt=Abstract
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FACS monitoring of lymphocyte-subsets in patients with discoid and subacutecutaneous lupus erythematosus receiving low-dose methotrexate. Author(s): Boehm I, Wenzel J. Source: Scandinavian Journal of Rheumatology. 2002; 31(4): 216-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369653&dopt=Abstract
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Factors affecting outcome and prognosis in membranous lupus nephropathy. Author(s): Mercadal L, Montcel ST, Nochy D, Queffeulou G, Piette JC, Isnard-Bagnis C, Martinez F. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 October; 17(10): 1771-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12270983&dopt=Abstract
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Failure to detect antibodies to the second extracellular loop of the serotonin 5-HT4 receptor in systemic lupus erythematosus and primary Sjogren's syndrome. Author(s): Cavill D, Waterman S, Gordon TP. Source: Lupus. 2002; 11(3): 197-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999887&dopt=Abstract
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False positive VDRL (BFP-STS) and systemic lupus erythematosus; new data in clinico-laboratory associations. Author(s): Al Attia HM. Source: International Journal of Dermatology. 2002 December; 41(12): 858-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492969&dopt=Abstract
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Familial lupus anticoagulant. Author(s): Tanaseanu C, Tanaseanu S. Source: Roum Arch Microbiol Immunol. 1999 July-December; 58(3-4): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11845463&dopt=Abstract
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Familial occurrence of autoimmune diseases and autoantibodies in a Caucasian population of patients with systemic lupus erythematosus. Author(s): Corporaal S, Bijl M, Kallenberg CG. Source: Clinical Rheumatology. 2002 May; 21(2): 108-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086159&dopt=Abstract
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Familial systemic lupus erythematosus: a comparison of clinical manifestations and antibody presentation in three ethnic groups. Author(s): Quintero-Del-Rio AI, Bacino D, Kelly J, Aberle T, Harley JB. Source: Cell Mol Biol (Noisy-Le-Grand). 2001 November; 47(7): 1223-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838971&dopt=Abstract
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Familial systemic lupus erythematosus: the role of genetic and environmental factors. Author(s): Eroglu GE, Kohler PF. Source: Annals of the Rheumatic Diseases. 2002 January; 61(1): 29-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779754&dopt=Abstract
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Familiality and co-occurrence of clinical features of systemic lupus erythematosus. Author(s): Tsao BP, Grossman JM, Riemekasten G, Strong N, Kalsi J, Wallace DJ, Chen CJ, Lau CS, Ginzler EM, Goldstein R, Kalunian KC, Harley JB, Arnett FC, Hahn BH, Cantor RM. Source: Arthritis and Rheumatism. 2002 October; 46(10): 2678-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384927&dopt=Abstract
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Family studies in systemic lupus erythematosus. Author(s): Alarcon-Riquelme ME. Source: Rheumatology (Oxford, England). 2002 April; 41(4): 364-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961164&dopt=Abstract
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Fas expression on peripheral blood lymphocytes in systemic lupus erythematosus (SLE): relation to lymphocyte activation and disease activity. Author(s): Bijl M, Horst G, Limburg PC, Kallenberg CG. Source: Lupus. 2001; 10(12): 866-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11787876&dopt=Abstract
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Fas promoter -670 polymorphism is associated with development of anti-RNP antibodies in systemic lupus erythematosus. Author(s): Lee YH, Kim YR, Ji JD, Sohn J, Song GG. Source: The Journal of Rheumatology. 2001 September; 28(9): 2008-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550967&dopt=Abstract
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Fatal evolution of systemic lupus erythematosus associated with Crohn's disease. Author(s): Chebli JM, Gaburri PD, de Souza AF, Dias KV, Cimino KO, de CarvalhoFilho RJ, Lucca FA. Source: Arquivos De Gastroenterologia. 2000 October-December; 37(4): 224-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11469224&dopt=Abstract
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Fatal Kikuchi-Fujimoto disease: the lupus connection. Author(s): Quintas-Cardama A, Fraga M, Cozzi SN, Caparrini A, Maceiras F, Forteza J. Source: Annals of Hematology. 2003 March; 82(3): 186-8. Epub 2003 February 22. Erratum In: Ann Hematol. 2003 June; 82(6): 377. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634955&dopt=Abstract
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Fatigue in daily life in patients with primary Sjogren's syndrome and systemic lupus erythematosus. Author(s): Godaert GL, Hartkamp A, Geenen R, Garssen A, Kruize AA, Bijlsma JW, Derksen RH. Source: Annals of the New York Academy of Sciences. 2002 June; 966: 320-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114289&dopt=Abstract
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Fatigue in patients with systemic lupus erythematosus: lack of associations to serum cytokines, antiphospholipid antibodies, or other disease characteristics. Author(s): Omdal R, Mellgren SI, Koldingsnes W, Jacobsen EA, Husby G. Source: The Journal of Rheumatology. 2002 March; 29(3): 482-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908560&dopt=Abstract
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Fatigue in patients with systemic lupus erythematosus: the psychosocial aspects. Author(s): Omdal R, Waterloo K, Koldingsnes W, Husby G, Mellgren SI. Source: The Journal of Rheumatology. 2003 February; 30(2): 283-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563681&dopt=Abstract
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Fcgamma and complement receptors: expression, role and co-operation in mediating the oxidative burst and degranulation of neutrophils of Brazilian systemic lupus erythematosus patients. Author(s): Marzocchi-Machado CM, Alves CM, Azzolini AE, Polizello AC, Carvalho IF, Lucisano-Valim YM. Source: Lupus. 2002; 11(4): 240-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043888&dopt=Abstract
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Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to genetic susceptibility. Author(s): Kyogoku C, Dijstelbloem HM, Tsuchiya N, Hatta Y, Kato H, Yamaguchi A, Fukazawa T, Jansen MD, Hashimoto H, van de Winkel JG, Kallenberg CG, Tokunaga K. Source: Arthritis and Rheumatism. 2002 May; 46(5): 1242-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115230&dopt=Abstract
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Fcgamma receptor IIa, IIIa, and IIIb polymorphisms in German patients with systemic lupus erythematosus: association with clinical symptoms. Author(s): Manger K, Repp R, Jansen M, Geisselbrecht M, Wassmuth R, Westerdaal NA, Pfahlberg A, Manger B, Kalden JR, van de Winkel JG. Source: Annals of the Rheumatic Diseases. 2002 September; 61(9): 786-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176802&dopt=Abstract
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Fcgamma receptor IIIA polymorphism in Korean patients with systemic lupus erythematosus. Author(s): Lee EB, Lee YJ, Baek HJ, Kang SW, Chung ES, Shin CH, Hong KM, Tsao BP, Hahn BH, Song YW. Source: Rheumatology International. 2002 April; 21(6): 222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036208&dopt=Abstract
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FcgammaRIIA, FcgammaRIIIA and FcgammaRIIIB polymorphisms in Spanish patients with systemic lupus erythematosus. Author(s): Gonzalez-Escribano MF, Aguilar F, Sanchez-Roman J, Nunez-Roldan A. Source: European Journal of Immunogenetics : Official Journal of the British Society for Histocompatibility and Immunogenetics. 2002 August; 29(4): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121275&dopt=Abstract
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FcgammaRIIa/IIIa polymorphism and its association with clinical manifestations in Korean lupus patients. Author(s): Yun HR, Koh HK, Kim SS, Chung WT, Kim DW, Hong KP, Song GG, Chang HK, Choe JY, Bae SC, Salmon JE, Yoo DH, Kim TY, Kim SY. Source: Lupus. 2001; 10(7): 466-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480843&dopt=Abstract
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Fibrothorax and severe lung restriction secondary to lupus pleuritis and its successful treatment by pleurectomy. Author(s): Sharma S, Smith R, Al-Hameed F. Source: Can Respir J. 2002 September-October; 9(5): 335-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410325&dopt=Abstract
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Flaccid paresis due to distal renal tubular acidosis preceding systemic lupus erythematosus. Author(s): Ter Meulen CG, Pieters GF, Huysmans FT. Source: The Netherlands Journal of Medicine. 2002 March; 60(1): 29-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074041&dopt=Abstract
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Flame figures in urticarial lesions accompanying systemic lupus erythematosus. Author(s): Wenzel J, Boehm I, Gerdsen R, Bieber T, Uerlich M. Source: The American Journal of Dermatopathology. 2001 December; 23(6): 533-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801796&dopt=Abstract
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Flares in patients with systemic lupus erythematosus are associated with daily psychological stress. Author(s): Pawlak CR, Witte T, Heiken H, Hundt M, Schubert J, Wiese B, BischoffRenken A, Gerber K, Licht B, Goebel MU, Heijnen CJ, Schmidt RE, Schedlowski M. Source: Psychotherapy and Psychosomatics. 2003 May-June; 72(3): 159-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707483&dopt=Abstract
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Flutamide-induced photosensitivity: is it a forme fruste of lupus? Author(s): Kaur C, Thami GP. Source: The British Journal of Dermatology. 2003 March; 148(3): 603-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653768&dopt=Abstract
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Foetal loss, liver necrosis and acute lupus erythematosus in a patient with antiphospholipid antibody syndrome. Author(s): Fehr T, Cathomas G, Weber C, Fontana A, Schaffner A. Source: Lupus. 2001; 10(8): 576-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11531001&dopt=Abstract
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Follicular lupus erythematosus: a new cutaneous manifestation of systemic lupus erythematosus. Author(s): Morihara K, Kishimoto S, Shibagaki R, Takenaka H, Yasuno H. Source: The British Journal of Dermatology. 2002 July; 147(1): 157-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100201&dopt=Abstract
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Free radical mediated peroxidative damage in systemic lupus erythematosus. Author(s): Kurien BT, Scofield RH. Source: Life Sciences. 2003 August 15; 73(13): 1655-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875898&dopt=Abstract
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Frequency and severity of systemic disease in patients with subacute cutaneous lupus erythematosus. Author(s): Black DR, Hornung CA, Schneider PD, Callen JP. Source: Archives of Dermatology. 2002 September; 138(9): 1175-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224978&dopt=Abstract
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Frequency of adverse drug reactions in patients with systemic lupus erythematosus. Author(s): Pope J, Jerome D, Fenlon D, Krizova A, Ouimet J. Source: The Journal of Rheumatology. 2003 March; 30(3): 480-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610805&dopt=Abstract
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Frequency of Mycoplasma hominis and Ureaplasma urealyticum infections in women with systemic lupus erythematosus. Author(s): Machado AA, Zorzi AR, Gleria AE, Donadi EA. Source: Revista Da Sociedade Brasileira De Medicina Tropical. 2001 May-June; 34(3): 243-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11460209&dopt=Abstract
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Frequent development of lupus anticoagulants in critically ill patients treated under intensive care conditions. Author(s): Wenzel C, Stoiser B, Locker GJ, Laczika K, Quehenberger P, Kapiotis S, Frass M, Pabinger I, Knobl P. Source: Critical Care Medicine. 2002 April; 30(4): 763-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11940742&dopt=Abstract
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Fulminant necrotising fasciitis developing during long term corticosteroid treatment of systemic lupus erythematosus. Author(s): Hashimoto N, Sugiyama H, Asagoe K, Hara K, Yamasaki O, Yamasaki Y, Makino H. Source: Annals of the Rheumatic Diseases. 2002 September; 61(9): 848-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176816&dopt=Abstract
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Functional defect of B lymphocytes in a patient with selective IgM deficiency associated with systemic lupus erythematosus. Author(s): Takeuchi T, Nakagawa T, Maeda Y, Hirano S, Sasaki-Hayashi M, Makino S, Shimizu A. Source: Autoimmunity. 2001; 34(2): 115-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11905841&dopt=Abstract
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Functional melanonychia due to involvement of the nail matrix in systemic lupus erythematosus. Author(s): Skowron F, Combemale P, Faisant M, Baran R, Kanitakis J, Dupin M. Source: Journal of the American Academy of Dermatology. 2002 August; 47(2 Suppl): S187-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140458&dopt=Abstract
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Gastrointestinal manifestations of systemic lupus erythematosus. Author(s): Luman W, Chua KB, Cheong WK, Ng HS. Source: Singapore Med J. 2001 August; 42(8): 380-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764057&dopt=Abstract
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Gender and age differences in systemic lupus erythematosus. A study of 489 Greek patients with a review of the literature. Author(s): Voulgari PV, Katsimbri P, Alamanos Y, Drosos AA. Source: Lupus. 2002; 11(11): 722-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475002&dopt=Abstract
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Gender differences in the clinical and serological features of systemic lupus erythematosus in Malaysian patients. Author(s): Azizah MR, Ainol SS, Kong NC, Normaznah Y, Rahim MN. Source: Med J Malaysia. 2001 September; 56(3): 302-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732074&dopt=Abstract
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Genes linked to severe lupus. Author(s): Cockey CD. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2003 April-May; 7(2): 108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735218&dopt=Abstract
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Genetic basis of systemic lupus erythematosus. Author(s): Hirose S, Jiang Y, Hamano Y, Nishimura H. Source: Drugs Today (Barc). 2002 March; 38(3): 167-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532173&dopt=Abstract
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Genetic basis of systemic lupus erythematosus: a review of the unique genetic contributions in African Americans. Author(s): Harley JB, Kelly JA. Source: Journal of the National Medical Association. 2002 August; 94(8): 670-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12152922&dopt=Abstract
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Genetic epidemiology: systemic lupus erythematosus. Author(s): Ahmad YA, Bruce IN. Source: Arthritis Research. 2001; 3(6): 331-6. Epub 2001 August 23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11714386&dopt=Abstract
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Genetic linkage and association of Fcgamma receptor IIIA (CD16A) on chromosome 1q23 with human systemic lupus erythematosus. Author(s): Edberg JC, Langefeld CD, Wu J, Moser KL, Kaufman KM, Kelly J, Bansal V, Brown WM, Salmon JE, Rich SS, Harley JB, Kimberly RP. Source: Arthritis and Rheumatism. 2002 August; 46(8): 2132-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209518&dopt=Abstract
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Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus. Author(s): Graham RR, Langefeld CD, Gaffney PM, Ortmann WA, Selby SA, Baechler EC, Shark KB, Ockenden TC, Rohlf KE, Moser KL, Brown WM, Gabriel SE, Messner RP, King RA, Horak P, Elder JT, Stuart PE, Rich SS, Behrens TW. Source: Arthritis Research. 2001; 3(5): 299-305. Epub 2001 July 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11549371&dopt=Abstract
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Genetic linkage of systemic lupus erythematosus with chromosome 11q14 (SLEH1) in African-American families stratified by a nucleolar antinuclear antibody pattern. Author(s): Sawalha AH, Namjou B, Nath SK, Kilpatrick J, Germundson A, Kelly JA, Hutchings D, James J, Harley J. Source: Genes and Immunity. 2002 October; 3 Suppl 1: S31-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215899&dopt=Abstract
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Genetically determined interferon-gamma production influences the histological phenotype of lupus nephritis. Author(s): Miyake K, Nakashima H, Akahoshi M, Inoue Y, Nagano S, Tanaka Y, Masutani K, Hirakata H, Gondo H, Otsuka T, Harada M. Source: Rheumatology (Oxford, England). 2002 May; 41(5): 518-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011374&dopt=Abstract
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Genetics of human lupus. Author(s): Kimberly RP. Source: Curr Dir Autoimmun. 1999; 1: 99-120. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791450&dopt=Abstract
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Genome scan stratified by the presence of anti-double-stranded DNA (dsDNA) autoantibody in pedigrees multiplex for systemic lupus erythematosus (SLE) establishes linkages at 19p13.2 (SLED1) and 18q21.1 (SLED2). Author(s): Namjou B, Nath SK, Kilpatrick J, Kelly JA, Reid J, Reichlin M, James JA, Harley JB. Source: Genes and Immunity. 2002 October; 3 Suppl 1: S35-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215900&dopt=Abstract
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Genome screening for susceptibility loci in systemic lupus erythematosus. Author(s): Shirai T, Nishimura H, Jiang Y, Hirose S. Source: American Journal of Pharmacogenomics : Genomics-Related Research in Drug Development and Clinical Practice. 2002; 2(1): 1-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083950&dopt=Abstract
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Geographical variation in mortality from systemic lupus erythematosus in the United States. Author(s): Walsh SJ, DeChello LM. Source: Lupus. 2001; 10(9): 637-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11678453&dopt=Abstract
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Gerstmann syndrome in systemic lupus erythematosus: neuropsychological, neuroimaging and spectroscopic findings. Author(s): Jung RE, Yeo RA, Sibbitt WL Jr, Ford CC, Hart BL, Brooks WM. Source: Neurocase : Case Studies in Neuropsychology, Neuropsychiatry, and Behavioural Neurology. 2001; 7(6): 515-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788743&dopt=Abstract
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Getting to the heart of the matter in systemic lupus and rheumatoid arthritis. Author(s): Manzi S, Wasko MC. Source: Bulletin on the Rheumatic Diseases. 2001; 50(5): 1-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387096&dopt=Abstract
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Glomerular and serum IgG subclasses in diffuse proliferative lupus nephritis, membranous lupus nephritis, and idiopathic membranous nephropathy. Author(s): Kuroki A, Shibata T, Honda H, Totsuka D, Kobayashi K, Sugisaki T. Source: Intern Med. 2002 November; 41(11): 936-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487163&dopt=Abstract
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Glomerular C4d deposition indicates in situ classic complement pathway activation, but is not a marker for lupus nephritis activity. Author(s): Kim SH, Jeong HJ. Source: Yonsei Medical Journal. 2003 February; 44(1): 75-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619178&dopt=Abstract
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Glomerular cell apoptosis in human lupus nephritis. Author(s): Makino H, Sugiyama H, Yamasaki Y, Maeshima Y, Wada J, Kashihara N. Source: Virchows Archiv : an International Journal of Pathology. 2003 July; 443(1): 67-77. Epub 2003 May 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750884&dopt=Abstract
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Glomerular expression of Fas ligand and Bax mRNA in lupus nephritis. Author(s): Badillo-Almaraz I, Daza L, Avalos-Diaz E, Herrera-Esparza R. Source: Autoimmunity. 2001; 34(4): 283-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11905854&dopt=Abstract
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Glutathione S-transferase M null homozygosity and risk of systemic lupus erythematosus associated with sun exposure: a possible gene-environment interaction for autoimmunity. Author(s): Fraser PA, Ding WZ, Mohseni M, Treadwell EL, Dooley MA, St Clair EW, Gilkeson GS, Cooper GS. Source: The Journal of Rheumatology. 2003 February; 30(2): 276-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563680&dopt=Abstract
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Gonadal function in adolescents and young women with juvenile systemic lupus erythematosus. Author(s): Silva CA, Leal MM, Leone C, Simone VP, Takiuti AD, Saito MI, Kiss MH. Source: Lupus. 2002; 11(7): 419-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195782&dopt=Abstract
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Gonadal function in male adolescents and young males with juvenile onset systemic lupus erythematosus. Author(s): Silva CA, Hallak J, Pasqualotto FF, Barba MF, Saito MI, Kiss MH. Source: The Journal of Rheumatology. 2002 September; 29(9): 2000-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233898&dopt=Abstract
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Granulocyte colony-stimulating factor therapy resulting in a flare of systemic lupus erythematosus: comment on the article by Yang and Hamilton. Author(s): Gottenberg JE, Roux S, Desmoulins F, Clerc D, Mariette X. Source: Arthritis and Rheumatism. 2001 October; 44(10): 2458-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11665994&dopt=Abstract
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Group psychotherapy reduces illness intrusiveness in systemic lupus erythematosus. Author(s): Edworthy SM, Dobkin PL, Clarke AE, Da Costa D, Dritsa M, Fortin PR, Barr S, Ensworth S, Esdaile JM, Beaulieu A, Zummer M, Senecal JL, Goulet JR, Choquette D, Rich E, Smith D, Cividino A, Gladman D, Devins GM. Source: The Journal of Rheumatology. 2003 May; 30(5): 1011-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734897&dopt=Abstract
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Guess what! Multiple disseminated dermatofibromas in a woman with systemic lupus erythematosus. Author(s): Niiyama S, Happle R, Hoffmann R. Source: Eur J Dermatol. 2001 September-October; 11(5): 475-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11525961&dopt=Abstract
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Haemophagocytic syndrome in a systemic lupus erythematosus patient with antiphospholipid antibodies. Author(s): Nawata M, Suzuki J, Ikeda K, Ando S, Koike M, Sekigawa I, Iida N, Wada R, Matsumoto M, Oshimi K, Hashimoto H. Source: Rheumatology (Oxford, England). 2001 July; 40(7): 828-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11477291&dopt=Abstract
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Hair dye treatment use and clinical course in patients with systemic lupus erythematosus and cutaneous lupus. Author(s): Jimenez-Alonso J, Sabio JM, Perez-Alvarez F, Reche I, Hidalgo C, Jaimez L; Grupo Lupus Virgen de las Nieves. Source: Lupus. 2002; 11(7): 430-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195784&dopt=Abstract
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Hematopoietic stem cell transplantation for severe and refractory lupus. Analysis after five years and fifteen patients. Author(s): Traynor AE, Barr WG, Rosa RM, Rodriguez J, Oyama Y, Baker S, Brush M, Burt RK. Source: Arthritis and Rheumatism. 2002 November; 46(11): 2917-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428232&dopt=Abstract
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Hematopoietic stem cell transplantation for severe and refractory lupus: comment on the article by Traynor et al. Author(s): Marmont AM. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2696-7; Author Reply 2697. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130494&dopt=Abstract
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Hemophagocytic syndrome in systemic lupus erythematosus. Author(s): Okada M, Suzuki K, Hidaka T, Shinohara T, Kataharada K, Matsumoto M, Takada K, Ohsuzu F. Source: Intern Med. 2001 December; 40(12): 1263-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11813858&dopt=Abstract
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Hemorrhagic complication of anticoagulation during pregnancy in a woman with lupus anticoagulant. Author(s): Casele HL, Laifer SA. Source: Obstetrics and Gynecology. 1997 October; 90(4 Pt 2): 646-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11770578&dopt=Abstract
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Hepatobiliary disease in neonatal lupus: prevalence and clinical characteristics in cases enrolled in a national registry. Author(s): Lee LA, Sokol RJ, Buyon JP. Source: Pediatrics. 2002 January; 109(1): E11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773579&dopt=Abstract
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High mass clearance of autoantibodies from a murine model of lupus nephritis by immunoadsorption using star-configured polyethylene glycols. Author(s): Ross EA, Branham ML, Tebbett IR. Source: Journal of Biomedical Materials Research. 2001 April; 55(1): 114-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11426388&dopt=Abstract
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High predictive value of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for survival in systemic lupus erythematosus. Author(s): Nived O, Jonsen A, Bengtsson AA, Bengtsson C, Sturfelt G. Source: The Journal of Rheumatology. 2002 July; 29(7): 1398-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136895&dopt=Abstract
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High prevalence of autoantibodies against the nuclear high mobility group (HMG) protein SSRP1 in sera from patients with systemic lupus erythematosus, but not other rheumatic diseases. Author(s): Santoro P, De AM, Migliaretti G, Trapani C, Landolfo S, Gariglio M. Source: The Journal of Rheumatology. 2002 January; 29(1): 90-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11824977&dopt=Abstract
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High-dose cyclophosphamide for severe systemic lupus erythematosus. Author(s): Gladstone DE, Prestrud AA, Pradhan A, Styler MJ, Topolsky DL, Crilley PA, Hoch S, Huppert A, Brodsky I. Source: Lupus. 2002; 11(7): 405-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195780&dopt=Abstract
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High-dose cyclophosphamide without stem cell transplantation in systemic lupus erythematosus. Author(s): Petri M, Jones RJ, Brodsky RA. Source: Arthritis and Rheumatism. 2003 January; 48(1): 166-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528116&dopt=Abstract
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Histiocytic necrotizing lymphadenitis preceding systemic lupus erythematosus. Author(s): Komocsi A, Tovari E, Pajor L, Czirjak L. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2001 September; 15(5): 476-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11763397&dopt=Abstract
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Histopathologic findings in lupus erythematosus tumidus: review of 80 patients. Author(s): Kuhn A, Sonntag M, Ruzicka T, Lehmann P, Megahed M. Source: Journal of the American Academy of Dermatology. 2003 June; 48(6): 901-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789183&dopt=Abstract
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HLA antigens in Malay patients with systemic lupus erythematosus: association with clinical and autoantibody expression. Author(s): Azizah MR, Ainol SS, Kong NC, Normaznah Y, Rahim MN. Source: Korean J Intern Med. 2001 June; 16(2): 123-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11590899&dopt=Abstract
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HLA class II DNA typing in a large series of European patients with systemic lupus erythematosus: correlations with clinical and autoantibody subsets. Author(s): Galeazzi M, Sebastiani GD, Morozzi G, Carcassi C, Ferrara GB, Scorza R, Cervera R, de Ramon Garrido E, Fernandez-Nebro A, Houssiau F, Jedryka-Goral A, Passiu G, Papasteriades C, Piette JC, Smolen J, Porciello G, Marcolongo R; European Concertee Action on the immunogenetics of SLE. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 2002 May; 81(3): 169-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11997714&dopt=Abstract
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HLA-DR expression on lymphocyte subsets as a marker of disease activity in patients with systemic lupus erythematosus. Author(s): Viallard JF, Bloch-Michel C, Neau-Cransac M, Taupin JL, Garrigue S, Miossec V, Mercie P, Pellegrin JL, Moreau JF. Source: Clinical and Experimental Immunology. 2001 September; 125(3): 485-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11531958&dopt=Abstract
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HLA-DR modulates autoantibody repertoire, but not mortality, in a humanized mouse model of systemic lupus erythematosus. Author(s): Paisansinsup T, Vallejo AN, Luthra H, David CS. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 October 1; 167(7): 4083-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564830&dopt=Abstract
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HLA-DRB alleles and systemic lupus erythematosus in Jamaicans. Author(s): Smikle M, Christian N, DeCeulaer K, Barton E, Roye-Green K, Dowe G, Anderson N, Nicholson G. Source: Southern Medical Journal. 2002 July; 95(7): 717-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12144077&dopt=Abstract
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HLA-DRB1 antigens in Taiwanese patients with juvenile-onset systemic lupus erythematosus. Author(s): Huang JL, Shaw CK, Lee A, Lee TD, Chou YH, Kuo ML. Source: Rheumatology International. 2001 November; 21(3): 103-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11765222&dopt=Abstract
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HLA-DRB1*03 and DQB1*0302 associations in a subset of patients severely affected with systemic lupus erythematosus from western India. Author(s): Shankarkumar U, Ghosh K, Badakere SS, Mohanty D. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 92-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480686&dopt=Abstract
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Homozygous single nucleotide polymorphism of the complement C1QA gene is associated with decreased levels of C1q in patients with subacute cutaneous lupus erythematosus. Author(s): Racila DM, Sontheimer CJ, Sheffield A, Wisnieski JJ, Racila E, Sontheimer RD. Source: Lupus. 2003; 12(2): 124-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630757&dopt=Abstract
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Hormonal and reproductive risk factors for development of systemic lupus erythematosus: results of a population-based, case-control study. Author(s): Cooper GS, Dooley MA, Treadwell EL, St Clair EW, Gilkeson GS. Source: Arthritis and Rheumatism. 2002 July; 46(7): 1830-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124867&dopt=Abstract
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Hospital experience and mortality in patients with systemic lupus erythematosus: which patients benefit most from treatment at highly experienced hospitals? Author(s): Ward MM. Source: The Journal of Rheumatology. 2002 June; 29(6): 1198-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064835&dopt=Abstract
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Hospitalizations for coronary artery disease among patients with systemic lupus erythematosus. Author(s): Thorburn CM, Ward MM. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2519-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130471&dopt=Abstract
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How “soft” are soft neurological signs? The relationship of subjective neuropsychiatric complaints to cognitive function in systemic lupus erythematosus. Author(s): Denburg SD, Stewart KE, Hart LE, Denburg JA. Source: The Journal of Rheumatology. 2003 May; 30(5): 1006-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734896&dopt=Abstract
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How does one assess and monitor patients with systemic lupus erythematosus in daily clinical practice? Author(s): Haq I, Isenberg DA. Source: Best Practice & Research. Clinical Rheumatology. 2002 April; 16(2): 181-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041948&dopt=Abstract
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How frequently are drugs associated with the development or exacerbation of subacute cutaneous lupus? Author(s): Callen JP. Source: Archives of Dermatology. 2003 January; 139(1): 89-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533174&dopt=Abstract
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How to manage patients with lupus nephritis. Author(s): Esdaile JM. Source: Best Practice & Research. Clinical Rheumatology. 2002 April; 16(2): 195-210. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041949&dopt=Abstract
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Human immunodeficiency virus infection and systemic lupus erythematosus. An unusual case and a review of the literature. Author(s): Palacios R, Santos J, Valdivielso P, Marquez M. Source: Lupus. 2002; 11(1): 60-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898923&dopt=Abstract
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Human parvovirus B19 infection mimicking systemic lupus erythematosus in an adult patient. Author(s): Negro A, Regolisti G, Perazzoli F, Coghi P, Tumiati B, Rossi E. Source: Ann Ital Med Int. 2001 April-June; 16(2): 125-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11688361&dopt=Abstract
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Human Ro60 (SSA2) genomic organization and sequence alterations, examined in cutaneous lupus erythematosus. Author(s): Millard TP, Ashton GH, Kondeatis E, Vaughan RW, Hughes GR, Khamashta MA, Hawk JL, McGregor JM, McGrath JA. Source: The British Journal of Dermatology. 2002 February; 146(2): 210-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11903229&dopt=Abstract
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Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebocontrolled study. Author(s): Levy RA, Vilela VS, Cataldo MJ, Ramos RC, Duarte JL, Tura BR, Albuquerque EM, Jesus NR. Source: Lupus. 2001; 10(6): 401-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434574&dopt=Abstract
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Hydroxychloroquine sulphate inhibits in vitro apoptosis of circulating lymphocytes in patients with systemic lupus erythematosus. Author(s): Liu ST, Wang CR, Yin GD, Liu MF, Lee GL, Chen MY, Chuang CY, Chen CY. Source: Asian Pac J Allergy Immunol. 2001 March; 19(1): 29-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11495297&dopt=Abstract
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Hydroxyethylstarch as a replacement fluid in therapeutic plasma exchange for lupus nephritis in a Jehovah's Witness. Author(s): Cid J, Ortin X, Elies E, Diaz E. Source: Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis. 2003 February; 28(1): 101-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620275&dopt=Abstract
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Hyperhomocysteinaemia and risk of thrombosis in systemic lupus erythematosus patients. Author(s): Refai TM, Al-Salem IH, Nkansa-Dwamena D, Al-Salem MH. Source: Clinical Rheumatology. 2002 November; 21(6): 457-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447627&dopt=Abstract
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Hyperprolactinaemia in patients with systemic lupus erythematosus. Author(s): Moszkorzova L, Lacinova Z, Marek J, Musilova L, Dohnalova A, Dostal C. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 807-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508772&dopt=Abstract
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Hypocomplementemic urticarial vasculitis: report of a 12-year-old girl with systemic lupus erythematosus. Author(s): DeAmicis T, Mofid MZ, Cohen B, Nousari HC. Source: Journal of the American Academy of Dermatology. 2002 November; 47(5 Suppl): S273-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399749&dopt=Abstract
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Hypophosphatemia in juvenile patients with systemic lupus erythematosus. Author(s): Fujiwara I, Ogawa E, Kondo Y, Ohura T, Iinuma K. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 February; 45(1): 23-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654064&dopt=Abstract
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Hyporesponsiveness to gammac-chain cytokines in activated lymphocytes from patients with systemic lupus erythematosus leads to accelerated apoptosis. Author(s): Lorenz HM, Grunke M, Hieronymus T, Winkler S, Blank N, Rascu A, Wendler J, Geiler T, Kalden JR. Source: European Journal of Immunology. 2002 May; 32(5): 1253-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981812&dopt=Abstract
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Hypothesis: can glucose-insulin-potassium regimen in combination with polyunsaturated fatty acids suppress lupus and other inflammatory conditions? Author(s): Das UN. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2001 August; 65(2): 10913. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545628&dopt=Abstract
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Identification of autoantibodies associated with systemic lupus erythematosus. Author(s): Lim Y, Lee DY, Lee S, Park SY, Kim J, Cho B, Lee H, Kim HY, Lee E, Song YW, Jeoung DI. Source: Biochemical and Biophysical Research Communications. 2002 July 5; 295(1): 11924. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083777&dopt=Abstract
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Identification of IgG subclasses and C-reactive protein in lupus nephritis: the relationship between the composition of immune deposits and FCgamma receptor type IIA alleles. Author(s): Zuniga R, Markowitz GS, Arkachaisri T, Imperatore EA, D'Agati VD, Salmon JE. Source: Arthritis and Rheumatism. 2003 February; 48(2): 460-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571856&dopt=Abstract
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Idiopathic intracranial hypertension with elevated cerebrospinal fluid level of interleukin-6 in a patient with systemic lupus erythematosus. Author(s): Komura K, Sato S, Ishida W, Fujii H, Takehara K. Source: Clinical Rheumatology. 2002 June; 21(3): 267-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111637&dopt=Abstract
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IgG anti-beta(2) glycoprotein I antibodies in Malaysian patients with antiphospholipid syndrome and systemic lupus erythematosus: prevalence and clinical correlations. Author(s): Ong SG, Cheng HM, Soon SC, Goh E, Chow SK, Yeap SS. Source: Clinical Rheumatology. 2002 September; 21(5): 382-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223986&dopt=Abstract
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IL-10 regulates murine lupus. Author(s): Yin Z, Bahtiyar G, Zhang N, Liu L, Zhu P, Robert ME, McNiff J, Madaio MP, Craft J. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 August 15; 169(4): 2148-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165544&dopt=Abstract
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IL-17 induces autoantibody overproduction and peripheral blood mononuclear cell overexpression of IL-6 in lupus nephritis patients. Author(s): Dong G, Ye R, Shi W, Liu S, Wang T, Yang X, Yang N, Yu X. Source: Chin Med J (Engl). 2003 April; 116(4): 543-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875719&dopt=Abstract
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Images and diagnoses. Discoid lupus erythematosus. (Chronic cutaneous lupus erythematosus). Author(s): Fitz-Henley M. Source: The West Indian Medical Journal. 2002 March; 51(1): 44, 52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089877&dopt=Abstract
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Images in cardiovascular medicine. Unusual manifestation of Libman-Sacks endocarditis in systemic lupus erythematosus. Author(s): Schneider C, Bahlmann E, Antz M, Bauer R, Reimers J, Raut W, Busch C, Rathjen F, Moll R, Kuck KH. Source: Circulation. 2003 June 10; 107(22): E202-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796416&dopt=Abstract
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Immune responses to native beta(2)-glycoprotein I in patients with systemic lupus erythematosus and the antiphospholipid syndrome. Author(s): Davies ML, Young SP, Welsh K, Bunce M, Wordsworth BP, Davies KA, Wagenknecht DR, Taylor E, Gordon C, Jobson S, Briggs D, Bowman SJ. Source: Rheumatology (Oxford, England). 2002 April; 41(4): 395-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961169&dopt=Abstract
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Immunopathogenesis of lupus and lupus nephritis: recent insights. Author(s): Kewalramani R, Singh AK. Source: Current Opinion in Nephrology and Hypertension. 2002 May; 11(3): 273-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981256&dopt=Abstract
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Immunopathology and the gene therapy of lupus. Author(s): Mageed RA, Prud'homme GJ. Source: Gene Therapy. 2003 May; 10(10): 861-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732872&dopt=Abstract
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Immunoserological changes in the cerebro-spinal fluid and serum in systemic lupus erythematosus patients with demyelinating syndrome and multiple sclerosis. Author(s): Baraczka K, Lakos G, Sipka S. Source: Acta Neurologica Scandinavica. 2002 May; 105(5): 378-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11982489&dopt=Abstract
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Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Author(s): Houssiau FA, Vasconcelos C, D'Cruz D, Sebastiani GD, Garrido Ed Ede R, Danieli MG, Abramovicz D, Blockmans D, Mathieu A, Direskeneli H, Galeazzi M, Gul A, Levy Y, Petera P, Popovic R, Petrovic R, Sinico RA, Cattaneo R, Font J, Depresseux G, Cosyns JP, Cervera R. Source: Arthritis and Rheumatism. 2002 August; 46(8): 2121-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209517&dopt=Abstract
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Impaired antioxidant status and decreased dietary intake of antioxidants in patients with systemic lupus erythematosus. Author(s): Bae SC, Kim SJ, Sung MK. Source: Rheumatology International. 2002 November; 22(6): 238-43. Epub 2002 September 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426662&dopt=Abstract
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Impaired clearance of apoptotic cells in systemic lupus erythematosus: challenge of T and B cell tolerance. Author(s): Kuenkele S, Beyer TD, Voll RE, Kalden JR, Herrmann M. Source: Curr Rheumatol Rep. 2003 June; 5(3): 175-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12744807&dopt=Abstract
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Importance of planning ovulation induction therapy in systemic lupus erythematosus and antiphospholipid syndrome: a single center retrospective study of 21 cases and 114 cycles. Author(s): Huong du LT, Wechsler B, Vauthier-Brouzes D, Duhaut P, Costedoat N, Lefebvre G, Piette JC. Source: Seminars in Arthritis and Rheumatism. 2002 December; 32(3): 174-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528082&dopt=Abstract
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Improved clinical outcome of lupus nephritis during the past decade: importance of early diagnosis and treatment. Author(s): Fiehn C, Hajjar Y, Mueller K, Waldherr R, Ho AD, Andrassy K. Source: Annals of the Rheumatic Diseases. 2003 May; 62(5): 435-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695156&dopt=Abstract
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Incidence and spectrum of neonatal lupus erythematosus: a prospective study of infants born to mothers with anti-Ro autoantibodies. Author(s): Cimaz R, Spence DL, Hornberger L, Silverman ED. Source: The Journal of Pediatrics. 2003 June; 142(6): 678-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838197&dopt=Abstract
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Inclusion body myositis evolving in systemic lupus erythrematosus? A case report. Author(s): Massawi G, Hickling P, Hilton D, Patterson C. Source: Rheumatology (Oxford, England). 2003 August; 42(8): 1012-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869675&dopt=Abstract
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Increased cancer incidence in a Swedish cohort of patients with systemic lupus erythematosus. Author(s): Bjornadal L, Lofstrom B, Yin L, Lundberg IE, Ekbom A. Source: Scandinavian Journal of Rheumatology. 2002; 31(2): 66-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109649&dopt=Abstract
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Increased expression of soluble cytotoxic T-lymphocyte-associated antigen-4 molecule in patients with systemic lupus erythematosus. Author(s): Liu MF, Wang CR, Chen PC, Fung LL. Source: Scandinavian Journal of Immunology. 2003 June; 57(6): 568-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791095&dopt=Abstract
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Increased frequency of pre-germinal center B cells and plasma cell precursors in the blood of children with systemic lupus erythematosus. Author(s): Arce E, Jackson DG, Gill MA, Bennett LB, Banchereau J, Pascual V. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 August 15; 167(4): 2361-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490026&dopt=Abstract
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Increased IL-18 in patients with systemic lupus erythematosus: relations with Th-1, Th-2, pro-inflammatory cytokines and disease activity. IL-18 is a marker of disease activity but does not correlate with pro-inflammatory cytokines. Author(s): Amerio P, Frezzolini A, Abeni D, Teofoli P, Girardelli CR, De Pita O, Puddu P. Source: Clin Exp Rheumatol. 2002 July-August; 20(4): 535-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12175109&dopt=Abstract
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Increased levels of interleukin-18 in patients with systemic lupus erythematosus: comment on the article by Shibatomi et al. Author(s): Tokano Y, Suzuki J, Amano H, Nozawa K, Morimoto S, Hashimoto H. Source: Arthritis and Rheumatism. 2002 May; 46(5): 1410-1; Author Reply 1411-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115256&dopt=Abstract
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Increased lung uptake of technetium-99m hexamethylpropylene amine oxime in systemic lupus erythematosus. Author(s): Shih CM, Shiau YC, Wang JJ, Ho ST, Kao A. Source: Respiration; International Review of Thoracic Diseases. 2002; 69(2): 143-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961428&dopt=Abstract
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Increased lymphocyte death by neglect-apoptosis is associated with lymphopenia and autoantibodies in lupus patients presenting with neuropsychiatric manifestations. Author(s): Silva LM, Garcia AB, Donadi EA. Source: Journal of Neurology. 2002 August; 249(8): 1048-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195452&dopt=Abstract
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Increased T-lymphocyte apoptosis/necrosis and IL-10 producing cells in patients and their spouses in Icelandic systemic lupus erythematosus multicase families. Author(s): Grondal G, Traustadottir KH, Kristjansdottir H, Lundberg I, Klareskog L, Erlendsson K, Steinsson K. Source: Lupus. 2002; 11(7): 435-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195785&dopt=Abstract
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Increased ubiquitination and reduced expression of LCK in T lymphocytes from patients with systemic lupus erythematosus. Author(s): Jury EC, Kabouridis PS, Abba A, Mageed RA, Isenberg DA. Source: Arthritis and Rheumatism. 2003 May; 48(5): 1343-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746907&dopt=Abstract
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Indocyanine green angiographic findings in systemic lupus erythematosus choroidopathy. Author(s): Gharbiya M, Bozzoni-Pantaleoni F, Augello F, Balacco-Gabrieli C. Source: American Journal of Ophthalmology. 2002 August; 134(2): 286-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140047&dopt=Abstract
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Induction of apoptosis in human blood T cells by 7,8-dihydroneopterin: the difference between healthy controls and patients with systemic lupus erythematosus. Author(s): Wirleitner B, Obermoser G, Bock G, Neurauter G, Schennach H, Sepp N, Fuchs D. Source: Clinical Immunology (Orlando, Fla.). 2003 June; 107(3): 152-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804528&dopt=Abstract
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Infantile cerebellar thrombosis: a case of lupus anticoagulants? Author(s): Bardella D, Rossi ML, Temporin G. Source: Pediatr Med Chir. 2002 September-October; 24(5): 392-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494544&dopt=Abstract
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Infection in Thai patients with systemic lupus erythematosus: a review of hospitalized patients. Author(s): Wongchinsri J, Tantawichien T, Osiri M, Akkasilpa S, Deesomchok U. Source: J Med Assoc Thai. 2002 June; 85 Suppl 1: S34-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12188433&dopt=Abstract
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Infections associated with juvenile systemic lupus erythematosus. Author(s): Al-Mayouf SM, Al-Jumaah S, Bahabri S, Al-Eid W. Source: Clin Exp Rheumatol. 2001 November-December; 19(6): 748-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791653&dopt=Abstract
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Infections in outpatients with systemic lupus erythematosus: a prospective study. Author(s): Zonana-Nacach A, Camargo-Coronel A, Yanez P, Sanchez L, JimenezBalderas FJ, Fraga A. Source: Lupus. 2001; 10(7): 505-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480850&dopt=Abstract
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Infections in systemic connective tissue diseases: systemic lupus erythematosus, scleroderma, and polymyositis/dermatomyositis. Author(s): Juarez M, Misischia R, Alarcon GS. Source: Rheumatic Diseases Clinics of North America. 2003 February; 29(1): 163-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635506&dopt=Abstract
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Infectious diseases in systemic lupus erythematosus: risk factors, management and prophylaxis. Author(s): Fessler BJ. Source: Best Practice & Research. Clinical Rheumatology. 2002 April; 16(2): 281-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041954&dopt=Abstract
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Inflammatory cytokine gene expression in the urinary sediment of patients with lupus nephritis. Author(s): Chan RW, Tam LS, Li EK, Lai FM, Chow KM, Lai KB, Li PK, Szeto CC. Source: Arthritis and Rheumatism. 2003 May; 48(5): 1326-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746905&dopt=Abstract
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Infliximab-induced systemic lupus erythematosus. Author(s): Ali Y, Shah S. Source: Annals of Internal Medicine. 2002 October 1; 137(7): 625-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353965&dopt=Abstract
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Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. Author(s): Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J, Pascual V. Source: The Journal of Experimental Medicine. 2003 March 17; 197(6): 711-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642603&dopt=Abstract
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Interferon-alpha: a new target for therapy in systemic lupus erythematosus? Author(s): Crow MK. Source: Arthritis and Rheumatism. 2003 September; 48(9): 2396-401. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130457&dopt=Abstract
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Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Author(s): Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, Shark KB, Grande WJ, Hughes KM, Kapur V, Gregersen PK, Behrens TW. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 March 4; 100(5): 2610-5. Epub 2003 February 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604793&dopt=Abstract
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Interferon-inducible p202 in the susceptibility to systemic lupus. Author(s): Choubey D, Kotzin BL. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2002 May 1; 7: E252-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991834&dopt=Abstract
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Interleukin-1 receptor antagonist gene polymorphism in chinese patients with systemic lupus erythematosus. Author(s): Huang CM, Wu MC, Wu JY, Tsai FJ. Source: Clinical Rheumatology. 2002 June; 21(3): 255-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111633&dopt=Abstract
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Interleukin-10 receptor expression in systemic lupus erythematosus and rheumatoid arthritis. Author(s): Cairns AP, Crockard AD, Bell AL. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 83-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673894&dopt=Abstract
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Intermittent epoprostenol infusions in systemic lupus erythematosus associated pulmonary hypertension--a series of three cases. Author(s): Kong KO, Badsha H, Thumboo J, Chng HH. Source: Ann Acad Med Singapore. 2003 January; 32(1): 118-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625109&dopt=Abstract
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Internuclear ophthalmoplegia (INO): an unusual presentation of neuropsychiatric lupus erythematosus. Author(s): Abel MP, Murphy FT, Enzenauer RJ, Enzenauer RW. Source: Binocul Vis Strabismus Q. 2003 Spring; 18(1): 29-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597766&dopt=Abstract
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Intestinal pseudo-obstruction in systemic lupus erythematosus. Author(s): Narvaez J, Perez-Vega C, Castro-Bohorquez FJ, Garcia-Quintana AM, Biosca M, Vilaseca-Momplet J. Source: Scandinavian Journal of Rheumatology. 2003; 32(3): 191-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892261&dopt=Abstract
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Intracardiac thrombosis and mitral prosthesis dysfunction in systemic lupus erythematosus. A case report. Author(s): da Silva AN, Ferreira LD, Monaco CG, Silva CE, Gil MA, Peixoto LB, Ortiz J. Source: Rev Port Cardiol. 2003 February; 22(2): 213-9. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769001&dopt=Abstract
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Intracranial hemorrhage in systemic lupus erythematosus associated with an autoantibody against actor XIII. Author(s): Lorand L, Velasco PT, Hill JM, Hoffmeister KJ, Kaye FJ. Source: Thrombosis and Haemostasis. 2002 December; 88(6): 919-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529739&dopt=Abstract
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Intramolecular epitope spreading among anti-caspase-8 autoantibodies in patients with silicosis, systemic sclerosis and systemic lupus erythematosus, as well as in healthy individuals. Author(s): Ueki A, Isozaki Y, Tomokuni A, Hatayama T, Ueki H, Kusaka M, Shiwa M, Arikuni H, Takeshita T, Morimoto K. Source: Clinical and Experimental Immunology. 2002 September; 129(3): 556-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197899&dopt=Abstract
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Intrathecal corticosteroids for systemic lupus erythematosus with central nervous system involvement. Author(s): Funauchi M, Ohno M, Nozaki Y, Sugiyama M, Kinoshita K, Kanamaru A. Source: The Journal of Rheumatology. 2003 January; 30(1): 207-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508419&dopt=Abstract
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Intravenous pulses of methylprednisolone for systemic lupus erythematosus. Author(s): Badsha H, Edwards CJ. Source: Seminars in Arthritis and Rheumatism. 2003 June; 32(6): 370-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833245&dopt=Abstract
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Invasive aspergillosis in juvenile systemic lupus erythematosus. A clinico-pathologic case. Author(s): Canova EG, Rosa DC, Vallada MG, Silva CA. Source: Clin Exp Rheumatol. 2002 September-October; 20(5): 736. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412216&dopt=Abstract
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Involvement of cytokines in the pathogenesis of systemic lupus erythematosus. Author(s): Lauwerys BR, Houssiau FA. Source: Advances in Experimental Medicine and Biology. 2003; 520: 237-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613582&dopt=Abstract
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Is acquired C1 inhibitor deficiency associated with lupus a distinct disease entity? Comment on the article by Cacoub et al. Author(s): Aslam A, Misbah SA. Source: Arthritis and Rheumatism. 2002 October; 46(10): 2827-8; Author Reply 2828. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12384953&dopt=Abstract
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Is it fibromyalgia? Is it lupus? Too much or not enough: comments related to women referred to a tertiary care academic rheumatology research and treatment center. Author(s): Alarcon GS. Source: Joint, Bone, Spine : Revue Du Rhumatisme. 2002 October; 69(5): 425-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477224&dopt=Abstract
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Ischaemic necrosis of the rectum and sigmoid colon complicating systemic lupus erythematosus. Author(s): Lazaris ACh, Papanikolaou IS, Theodoropoulos GE, Petraki K, Davaris PS. Source: Acta Gastroenterol Belg. 2003 April-June; 66(2): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891932&dopt=Abstract
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Ischemic colitis, systemic lupus erythematosus, and the lupus anticoagulant: case report and review. Author(s): Richardson SC, Willis J, Wong RC. Source: Gastrointestinal Endoscopy. 2003 February; 57(2): 257-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556799&dopt=Abstract
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Isolation and functional analysis of autoreactive T cells from BXSB mice with murine lupus. Author(s): Han SH, Li B, Chen YT, Gao XM. Source: Journal of Autoimmunity. 2002 August-September; 19(1-2): 45-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367558&dopt=Abstract
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Item weightings for the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Disease Damage Index using Rasch analysis do not lead to an important improvement. Author(s): Brunner HI, Feldman BM, Urowitz MB, Gladman DD. Source: The Journal of Rheumatology. 2003 February; 30(2): 292-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563683&dopt=Abstract
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Jaccoud's arthropathy in systemic lupus erythematosus: differentiation of deforming and erosive patterns by magnetic resonance imaging. Author(s): Ostendorf B, Scherer A, Specker C, Modder U, Schneider M. Source: Arthritis and Rheumatism. 2003 January; 48(1): 157-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12528115&dopt=Abstract
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Juvenile parkinsonism as a manifestation of systemic lupus erythematosus: case report and review of the literature. Author(s): Garcia-Moreno JM, Chacon J. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2002 November; 17(6): 1329-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465077&dopt=Abstract
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Kienbock's disease in systemic lupus erythematosus. Author(s): Taniguchi Y, Tamaki T, Yoshida M. Source: Hand Surgery : an International Journal Devoted to Hand and Upper Limb Surgery and Related Research : Journal of the Asia-Pacific Federation of Societies for Surgery of the Hand. 2002 December; 7(2): 197-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12596279&dopt=Abstract
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Kikuchi-Fujimoto's disease, histiocytic necrotizing lymphadenitis, mimicking systemic lupus erythematosus. Author(s): Mootsikapun P, Sirijerachai J, Nanagara R. Source: J Med Assoc Thai. 2002 September; 85(9): 1037-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450085&dopt=Abstract
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Kikuchi's disease accompanied by lupus-like butterfly rash. Author(s): Okuzawa C, Kuroiwa T, Kaneko Y, Ueki K, Tsukada Y, Nojima Y. Source: The Journal of Rheumatology. 2003 April; 30(4): 857-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672213&dopt=Abstract
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Kikuchi's disease, skin and systemic lupus erythematosus. Author(s): Kaur S, Thami GP, Kanwar AJ. Source: The British Journal of Dermatology. 2002 January; 146(1): 167-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11852921&dopt=Abstract
184 Lupus
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Kinetics of prothrombin-mediated binding of lupus anticoagulant antibodies to phosphatidylserine-containing phospholipid membranes: an ellipsometric study. Author(s): Willems GM, Janssen MP, Comfurius P, Galli M, Zwaal RF, Bevers EM. Source: Biochemistry. 2002 December 3; 41(48): 14357-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450402&dopt=Abstract
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Kinin system in lupus nephritis. Author(s): Dellalibera-Joviliano R, Reis ML, Donadi EA. Source: International Immunopharmacology. 2001 September; 1(9-10): 1889-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11562080&dopt=Abstract
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Kinins and cytokines in plasma and cerebrospinal fluid of patients with neuropsychiatric lupus. Author(s): Dellalibera-Joviliano R, Dos Reis ML, Cunha Fde Q, Donadi EA. Source: The Journal of Rheumatology. 2003 March; 30(3): 485-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610806&dopt=Abstract
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KU 70/80 lupus autoantigen is the transcription factor induced by interleukins (IL)-13 and -4 leading to induction of 15-lipoxygenase (15-LO) in human cells. Author(s): Kelavkar U, Wang S, Badr K. Source: Advances in Experimental Medicine and Biology. 2002; 507: 469-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664628&dopt=Abstract
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Laboratory and field experiments used to identify Canis lupus var. familiaris active odor signature chemicals from drugs, explosives, and humans. Author(s): Lorenzo N, Wan T, Harper RJ, Hsu YL, Chow M, Rose S, Furton KG. Source: Analytical and Bioanalytical Chemistry. 2003 August; 376(8): 1212-24. Epub 2003 July 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845400&dopt=Abstract
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Laboratory diagnosis of lupus anticoagulants for patients on oral anticoagulant treatment. Performance of dilute Russell viper venom test and silica clotting time in comparison with Staclot LA. Author(s): Tripodi A, Chantarangkul V, Clerici M, Mannucci PM. Source: Thrombosis and Haemostasis. 2002 October; 88(4): 583-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362227&dopt=Abstract
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Laboratory diagnosis of lupus anticoagulants--effect of residual platelets in plasma, assessed by Staclot LA and silica clotting time. Author(s): Chantarangkul V, Tripodi A, Clerici M, Bressi C, Mannucci PM. Source: Thrombosis and Haemostasis. 2002 May; 87(5): 854-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12038789&dopt=Abstract
Studies 185
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Laboratory identification of lupus anticoagulants using the combination of activated partial thromboplastin time and Russell's viper venom at two phospholipid concentrations. Author(s): Akkawat B, Chantarangkul V, Rojnuckarin P, Juntiang J. Source: J Med Assoc Thai. 2003 June; 86 Suppl 2: S451-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930024&dopt=Abstract
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Lack of association between arylamine N-acetyltransferase 2 (NAT2) polymorphism and systemic lupus erythematosus. Author(s): Zschieschang P, Hiepe F, Gromnica-Ihle E, Roots I, Cascorbi I. Source: Pharmacogenetics. 2002 October; 12(7): 559-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360107&dopt=Abstract
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Lack of association between hyperprolactinemia and soluble IL-2 receptor levels in systemic lupus erythematosus. Author(s): Daza L, Lavalle C, Duarte C, Huerta R, Moreno J. Source: Lupus. 2003; 12(2): 107-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630754&dopt=Abstract
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Lack of deleterious somatic mutations in the CD95 gene of plasmablasts from systemic lupus erythematosus patients and autoantibody-producing cell lines. Author(s): Kurth J, Perniok A, Schmitz R, Iking-Konert C, Chiorazzi N, Thompson KM, Winkler T, Rajewsky K, Kuppers R. Source: European Journal of Immunology. 2002 December; 32(12): 3785-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12516573&dopt=Abstract
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Lack of the transcriptional coactivator OBF-1 prevents the development of systemic lupus erythematosus-like phenotypes in Aiolos mutant mice. Author(s): Sun J, Matthias G, Mihatsch MJ, Georgopoulos K, Matthias P. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 February 15; 170(4): 1699706. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574333&dopt=Abstract
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Langerhans cell histiocytosis in a patient with systemic lupus erythematosus: a clonal disease responding to treatment with cladribine, and cyclophosphamide. Author(s): Robak T, Kordek R, Robak E, Bartkowiak J, Biernat W, Liberski P, Blonski J. Source: Leukemia & Lymphoma. 2002 October; 43(10): 2041-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481906&dopt=Abstract
186 Lupus
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Late corneal scarring after photorefractive keratectomy concurrent with development of systemic lupus erythematosus. Author(s): Cua IY, Pepose JS. Source: Journal of Refractive Surgery (Thorofare, N.J. : 1995). 2002 November-December; 18(6): 750-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458872&dopt=Abstract
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Lessons from the “Euro-Lupus Cohort”. Author(s): Cervera R, Abarca-Costalago M, Abramovicz D, Allegri F, Annunziata P, Aydintug AO, Bacarelli MR, Bellisai F, Bernardino I, Biernat-Kaluza E, Blockmans D, Boki K, Bracci L, Campanella V, Camps MT, Carcassi C, Cattaneo R, Cauli A, Chwalinska-Sadowska H, Contu L, Cosyns JP, Danieli MG, D'Cruz D, Depresseux G, Direskeneli H, Domenech I, Espinosa G, Fernandez-Nebro A, Ferrara GB, Font J, Frutos MA, Galeazzi M, Garcia-Carrasco M, Garcia-Iglesias MF, Garcia-Tobaruela A, George J, Gil A, Gonzalez-Santos P, Grana M, Gul A, Haga HJ, de Haro-Liger M, Houssiau F, Hughes GR, Ingelmo M, Jedryka-Goral A, Khamashta MA, Lavilla P, Levi Y, LopezDupla M, Lopez-Soto A, Maldykowa H, Marcolongo R, Mathieu A, Morozzi G, Nicolopoulou N, Papasteriades C, Passiu G, Perello I, Petera P, Petrovic R, Piette JC, Pintado V, de Pita O, Popovic R, Pucci G, Puddu P, de Ramon E, Ramos-Casals M, Rodriguez-Andreu J, Ruiz-Irastroza G, Sanchez-Lora J, Sanna G, Scorza R, Sebastini GD, Sherer Y, Shoenfeld Y, Simpatico A, Sinico RA, Smolen J, Tincani A, Tokgoz G, UrbanoMarquez A, Vasconcelos C, Vazquez JJ, Veronesi M, Vianni J, Vivancos J; European Working Party on Systemic Lupus Erythematosus. Source: Annales De Medecine Interne. 2002 December; 153(8): 530-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610427&dopt=Abstract
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Leukocytoclastic vasculitis presenting as an erythema gyratum repens--like eruption on a patient with systemic lupus erythematosus. Author(s): Pique E, Palacios S, Santana Z. Source: Journal of the American Academy of Dermatology. 2002 November; 47(5 Suppl): S254-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399742&dopt=Abstract
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Levels of tissue factor pathway inhibitor in lupus patients correlate with lupus activity and endothelial damage markers. Author(s): Roldan V, Marco P, Fernandez C, Pascual E. Source: Haematologica. 2002 November; 87(11): 1231-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414358&dopt=Abstract
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Life-threatening extrarenal lupus in children despite improvement in serologic findings. Author(s): Butani L, Makker SP. Source: Rheumatology International. 2003 March; 23(2): 92-5. Epub 2003 February 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634943&dopt=Abstract
Studies 187
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Linear childhood cutaneous lupus erythematosus following Blaschko lines. Author(s): Requena C, Torrelo A, de Prada I, Zambrano A. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2002 November; 16(6): 618-20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482048&dopt=Abstract
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Linear lupus erythematosus profundus on the scalp following the lines of Blaschko. Author(s): Nagai Y, Ishikawa O, Hattori T, Ogawa T. Source: Eur J Dermatol. 2003 May-June; 13(3): 294-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804993&dopt=Abstract
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Linkage and interaction of loci on 1q23 and 16q12 may contribute to susceptibility to systemic lupus erythematosus. Author(s): Tsao BP, Cantor RM, Grossman JM, Kim SK, Strong N, Lau CS, Chen CJ, Shen N, Ginzler EM, Goldstein R, Kalunian KC, Arnett FC, Wallace DJ, Hahn BH. Source: Arthritis and Rheumatism. 2002 November; 46(11): 2928-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428234&dopt=Abstract
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LJP 394 for the prevention of renal flare in patients with systemic lupus erythematosus: results from a randomized, double-blind, placebo-controlled study. Author(s): Alarcon-Segovia D, Tumlin JA, Furie RA, McKay JD, Cardiel MH, Strand V, Bagin RG, Linnik MD, Hepburn B; LJP 394 Investigator Consortium. Source: Arthritis and Rheumatism. 2003 February; 48(2): 442-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571854&dopt=Abstract
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Long-term complications of systemic lupus erythematosus. Author(s): Gordon C. Source: Rheumatology (Oxford, England). 2002 October; 41(10): 1095-100. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364626&dopt=Abstract
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Long-term effectiveness of danazol corticosteroids and cytotoxic drugs in the treatment of hematologic manifestations of systemic lupus erythematosus. Author(s): Avina-Zubieta JA, Galindo-Rodriguez G, Robledo I, Vela-Ojeda J, VadilloBuenfil M, Rosas-Cabral A, Salazar-Exaire D. Source: Lupus. 2003; 12(1): 52-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587827&dopt=Abstract
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Longterm followup of childhood lupus nephritis. Author(s): Hagelberg S, Lee Y, Bargman J, Mah G, Schneider R, Laskin C, Eddy A, Gladman D, Urowitz M, Hebert D, Silverman E. Source: The Journal of Rheumatology. 2002 December; 29(12): 2635-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465165&dopt=Abstract
188 Lupus
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Long-term followup of children with neonatal lupus and their unaffected siblings. Author(s): Martin V, Lee LA, Askanase AD, Katholi M, Buyon JP. Source: Arthritis and Rheumatism. 2002 September; 46(9): 2377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355485&dopt=Abstract
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Long-term outcome in lupus nephritis. Author(s): Spiera RF, Homel P, Spiera H. Source: Annals of Internal Medicine. 2002 September 17; 137(6): 545-6; Author Reply 545-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230360&dopt=Abstract
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Low values of creatine kinase in systemic lupus erythematosus. Clinical significance in 300 patients. Author(s): Font J, Ramos-Casals M, Vilas AP, Garcia-Carrasco M, Brito MP, de la Red G, Gil V, Garcia-Carrasco A, Cervera R, Ingelmo M. Source: Clin Exp Rheumatol. 2002 November-December; 20(6): 837-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508777&dopt=Abstract
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Low-dose pulse cyclophosphamide in the treatment of neuropsychiatric lupus. Author(s): Sanna G, Khamashta MA, Sanni G. Source: Lupus. 2003; 12(1): 1-2. Review. Erratum In: Lupus. 2003; 12(4): 340. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587818&dopt=Abstract
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Low-dose thalidomide is an effective second-line treatment in cutaneous lupus erythematosus. Author(s): Thomson KF, Goodfield MJ. Source: The Journal of Dermatological Treatment. 2001 September; 12(3): 145-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12243705&dopt=Abstract
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Low-dose thalidomide therapy for refractory cutaneous lesions of lupus erythematosus. Author(s): Housman TS, Jorizzo JL, McCarty MA, Grummer SE, Fleischer AB Jr, Sutej PG. Source: Archives of Dermatology. 2003 January; 139(1): 50-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533164&dopt=Abstract
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Lupus and desoxyribonuclease. Author(s): Lachmann PJ. Source: Lupus. 2003; 12(3): 202-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708782&dopt=Abstract
Studies 189
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Lupus and zoster. Author(s): Douglas KM, Gordon C, Osman H, Heaton S, Skan J, Situnayake D, Bowman SJ. Source: Lancet. 2003 August 23; 362(9384): 616. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944061&dopt=Abstract
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Lupus anticoagulant associated with transient severe factor X deficiency: a report of two patients presenting with major bleeding complications. Author(s): Ashrani AA, Aysola A, Al-Khatib H, Nichols WL, Key NS. Source: British Journal of Haematology. 2003 May; 121(4): 639-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752106&dopt=Abstract
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Lupus anticoagulant presenting as a stroke in young. Author(s): Jani C, Bichile SK, Sampat N, Thacker H. Source: J Assoc Physicians India. 1997 April; 45(4): 329-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521098&dopt=Abstract
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Lupus anticoagulant testing: improvements in performance in a UK NEQAS proficiency testing exercise after dissemination of national guidelines on laboratory methods. Author(s): Jennings I, Greaves M, Mackie IJ, Kitchen S, Woods TA, Preston FE; UK National External Quality Assessment Scheme for Blood Coagulation. Source: British Journal of Haematology. 2002 November; 119(2): 364-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406070&dopt=Abstract
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Lupus anticoagulant-like activity observed in a dimeric lambda protein produced by myeloma cells. Author(s): Shinagawa A, Kojima H, Kobayashi T, Kawada K, Nagasawa T. Source: International Journal of Hematology. 2001 June; 73(4): 526-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11503969&dopt=Abstract
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Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Author(s): Galli M, Luciani D, Bertolini G, Barbui T. Source: Blood. 2003 March 1; 101(5): 1827-32. Epub 2002 October 03. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393574&dopt=Abstract
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Lupus anticoagulants: diagnosis and management. Author(s): Triplett DA. Source: Curr Hematol Rep. 2003 July; 2(4): 271-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901323&dopt=Abstract
190 Lupus
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Lupus autoantibodies 101: one size does not fit all; however, specificity influences pathogenicity. Author(s): Madaio MP. Source: Clinical and Experimental Immunology. 2003 March; 131(3): 396-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605690&dopt=Abstract
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Lupus autoantibodies recognize the product of an alternative open reading frame of SmB/B'. Author(s): Kaufman KM, Kirby MY, McClain MT, Harley JB, James JA. Source: Biochemical and Biophysical Research Communications. 2001 August 3; 285(5): 1206-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11478783&dopt=Abstract
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Lupus choroidopathy and choroidal effusions. Author(s): Lavina AM, Agarwal A, Hunyor A, Gass JD. Source: Retina (Philadelphia, Pa.). 2002 October; 22(5): 643-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441734&dopt=Abstract
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Lupus erythematosus associated with C1 inhibitor deficiency. Author(s): Koide M, Shirahama S, Tokura Y, Takigawa M, Hayakawa M, Furukawa F. Source: The Journal of Dermatology. 2002 August; 29(8): 503-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227484&dopt=Abstract
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Lupus erythematosus cells in the cutaneous lesion of overlap syndrome of dermatomyositis-SLE-like disease. Author(s): Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK, Lee EY. Source: The American Journal of Dermatopathology. 2003 June; 25(3): 272-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775993&dopt=Abstract
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Lupus erythematosus. What's new? Author(s): Jablonska S, Blaszczyk M. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2000 March; 15(2): 103-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11495512&dopt=Abstract
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Lupus erythematosus/lichen planus overlap syndrome with scarring alopecia. Author(s): Inaloz HS, Chowdhury MM, Motley RJ. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2000 March; 15(2): 171-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11495530&dopt=Abstract
Studies 191
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Lupus miliaris disseminatus faciei and its debated link to tuberculosis. Author(s): Nino M, Barberio E, Delfino M. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 January; 17(1): 97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602984&dopt=Abstract
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Lupus miliaris disseminatus faciei: a distinctive rosacea-like syndrome and not a granulomatous form of rosacea. Author(s): van de Scheur MR, van der Waal RI, Starink TM. Source: Dermatology (Basel, Switzerland). 2003; 206(2): 120-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592078&dopt=Abstract
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Lupus myelopathy in a child. Author(s): Vieira JP, Ortet O, Barata D, Abranches M, Gomes JM. Source: Pediatric Neurology. 2002 October; 27(4): 303-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435571&dopt=Abstract
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Lupus nephritis: a nucleosome waste disposal defect? Author(s): Berden JH, Grootscholten C, Jurgen WC, van der Vlag J. Source: Journal of Nephrology. 2002 November-December; 15 Suppl 6: S1-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515368&dopt=Abstract
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Lupus nephritis: current issues. Author(s): Mavragani CP, Moutsopoulos HM. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 795-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922947&dopt=Abstract
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Lupus nephritis: histopathologic features, classification and histologic scoring in renal biopsy. Author(s): Dimitrijevic J, Dukanovic L, Kovacevic Z, Bogdanovic R, Maksic D, Hrvacevic R, Aleksic A, Naumovic R, Jovanovic D, Brajuskovic G, Milosavljevic I. Source: Vojnosanit Pregl. 2002 November-December; 59(6 Suppl): 21-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852143&dopt=Abstract
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Lupus pregnancy. Author(s): Lockshin MD, Sammaritano LR. Source: Autoimmunity. 2003 February; 36(1): 33-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765469&dopt=Abstract
192 Lupus
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Lupus profundus: not a benign disease. Author(s): Grossberg E, Scherschun L, Fivenson DP. Source: Lupus. 2001; 10(7): 514-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480852&dopt=Abstract
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Lupus retinopathy associated with a high IFN-alpha level in the cerebrospinal fluid. Author(s): Kondo M, Murakawa Y, Sumita Y, Masuda H, Kobayashi S. Source: Intern Med. 2002 September; 41(9): 754-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12322808&dopt=Abstract
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Lupus vulgaris developing at the site of misdiagnosed scrofuloderma. Author(s): Motta A, Feliciani C, Toto P, De Benedetto A, Morelli F, Tulli A. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 May; 17(3): 313-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702074&dopt=Abstract
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Lupus vulgaris in a skin graft. Author(s): Bock M, Nolte O, Hartschuh W, Jappe U. Source: Acta Dermato-Venereologica. 2003; 83(2): 132-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735643&dopt=Abstract
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Lupus vulgaris mimicking lichen simplex chronicus. Author(s): Pandhi D, Reddy BS. Source: The Journal of Dermatology. 2001 July; 28(7): 369-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11510504&dopt=Abstract
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Lupus: tinkering with haematopoietic stem cells. Author(s): Marmont AM. Source: Lupus. 2001; 10(11): 769-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789484&dopt=Abstract
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Lupus-associated toxic epidermal necrolysis: a novel manifestation of lupus? Author(s): Mandelcorn R, Shear NH. Source: Journal of the American Academy of Dermatology. 2003 April; 48(4): 525-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664014&dopt=Abstract
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Lupus-like syndrome and vasculitis induced by valpromide. Author(s): Bonnet F, Morlat P, De Witte S, Combe C, Beylot J. Source: The Journal of Rheumatology. 2003 January; 30(1): 208-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508420&dopt=Abstract
Studies 193
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Lupus-specific kidney deposits of HSP90 are associated with altered IgG idiotypic interactions of anti-HSP90 autoantibodies. Author(s): Kenderov A, Minkova V, Mihailova D, Giltiay N, Kyurkchiev S, Kehayov I, Kazatchkine M, Kaveri S, Pashov A. Source: Clinical and Experimental Immunology. 2002 July; 129(1): 169-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100037&dopt=Abstract
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Lymphocytic interstitial pneumonitis associated with Epstein-Barr virus in Systemic Lupus Erythematosus and Sjogren's Syndrome. Complete remission with corticosteriod and cyclophosphamide. Author(s): Yum HK, Kim ES, Ok KS, Lee HK, Choi SJ. Source: Korean J Intern Med. 2002 September; 17(3): 198-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12298431&dopt=Abstract
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Major peptide autoepitopes for nucleosome-centered T and B cell interaction in human and murine lupus. Author(s): Datta SK. Source: Annals of the New York Academy of Sciences. 2003 April; 987: 79-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727626&dopt=Abstract
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Malignancies during follow-up in an epidemiologically defined systemic lupus erythematosus inception cohort in southern Sweden. Author(s): Nived O, Bengtsson A, Jonsen A, Sturfelt G, Olsson H. Source: Lupus. 2001; 10(7): 500-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480849&dopt=Abstract
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Malignancy and systemic lupus erythematosus. Author(s): Bernatsky S, Clarke A, Ramsey-Goldman R. Source: Curr Rheumatol Rep. 2002 August; 4(4): 351-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126588&dopt=Abstract
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Management of lupus erythematosus: recent insights. Author(s): Wallace DJ. Source: Current Opinion in Rheumatology. 2002 May; 14(3): 212-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981315&dopt=Abstract
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Management of lupus nephropathy. Author(s): Hebert LA. Source: Nephron. Clinical Practice [electronic Resource]. 2003 January; 93(1): C7-C12. Review. Erratum In: Nephron Clin Pract. 2003; 93(2): C74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411753&dopt=Abstract
194 Lupus
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Management of skin disease in patients with lupus erythematosus. Author(s): Callen JP. Source: Best Practice & Research. Clinical Rheumatology. 2002 April; 16(2): 245-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041952&dopt=Abstract
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Managing subacute cutaneous lupus erythematosus. Author(s): Pullen RL Jr. Source: Dermatology Nursing / Dermatology Nurses' Association. 2001 December; 13(6): 419-20, 423-6; Quiz 427. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837179&dopt=Abstract
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Mannose binding lectin and FcgammaRIIa (CD32) polymorphism in Spanish systemic lupus erythematosus patients. Author(s): Villarreal J, Crosdale D, Ollier W, Hajeer A, Thomson W, Ordi J, Balada E, Villardell M, Teh LS, Poulton K. Source: Rheumatology (Oxford, England). 2001 September; 40(9): 1009-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561111&dopt=Abstract
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Mannose binding lectin polymorphisms as a disease-modulating factor in women with systemic lupus erythematosus from Canary Islands, Spain. Author(s): Garcia-Laorden MI, Rua-Figueroa I, Perez-Aciego P, Rodriguez-Perez JC, Citores MJ, Alamo F, Erausquin C, Rodriguez-Gallego C. Source: The Journal of Rheumatology. 2003 April; 30(4): 740-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672193&dopt=Abstract
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Many paths lead to lupus. Author(s): Lawman S, Ehrenstein MR. Source: Lupus. 2002; 11(12): 801-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529045&dopt=Abstract
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Maternal antiphospholipid syndrome presenting as neonatal lupus with congenital complete heart block in the fetus. Author(s): Abu-Ras R, Felser K, Rottem M. Source: Isr Med Assoc J. 2001 December; 3(12): 966-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794929&dopt=Abstract
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MCP-1 promoter polymorphism in Spanish patients with systemic lupus erythematosus. Author(s): Aguilar F, Gonzalez-Escribano MF, Sanchez-Roman J, Nunez-Roldan A. Source: Tissue Antigens. 2001 November; 58(5): 335-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844145&dopt=Abstract
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Measuring disease activity in systemic lupus: progress and problems. Author(s): Merrill JT. Source: The Journal of Rheumatology. 2002 November; 29(11): 2256-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415577&dopt=Abstract
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Mediators of injury in lupus nephritis. Author(s): Oates JC, Gilkeson GS. Source: Current Opinion in Rheumatology. 2002 September; 14(5): 498-503. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192244&dopt=Abstract
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Melioidosis in systemic lupus erythematosus: the importance of early diagnosis and treatment in patients from endemic areas. Author(s): Badsha H, Edwards CJ, Chng HH. Source: Lupus. 2001; 10(11): 821-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789494&dopt=Abstract
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Membranous lupus nephritis in a renal allograft: response to mycophenolate mofetil therapy. Author(s): Denton MD, Galvanek EG, Singh A, Sayegh MH. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2001 September; 1(3): 288-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102264&dopt=Abstract
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Membranous nephropathy and seronegative systemic lupus erythematosus. Author(s): Cobenas CJ, Spizziri FD, Drut R. Source: Pediatric Nephrology (Berlin, Germany). 2003 February; 18(2): 202-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632595&dopt=Abstract
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Menstrual disturbances in patients with systemic lupus erythematosus without alkylating therapy: clinical, hormonal and therapeutic associations. Author(s): Pasoto SG, Mendonca BB, Bonfa E. Source: Lupus. 2002; 11(3): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999882&dopt=Abstract
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Mesangial cell-binding anti-DNA antibodies in patients with systemic lupus erythematosus. Author(s): Chan TM, Leung JK, Ho SK, Yung S. Source: Journal of the American Society of Nephrology : Jasn. 2002 May; 13(5): 1219-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961009&dopt=Abstract
196 Lupus
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Metabolic abnormalities associated with microalbuminuria in systemic lupus erythematosus. Author(s): Tam LS, Li EK, Benzie IF, Lam CW, Arumanayagam M, Chung WY, Tomlinson B. Source: Rheumatology (Oxford, England). 2001 October; 40(10): 1193-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11600754&dopt=Abstract
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Metastatic silicone granuloma: lupus miliaris disseminatus faciei-like facial nodules and sicca complex in a silicone breast implant recipient. Author(s): Suzuki K, Aoki M, Kawana S, Hyakusoku H, Miyazawa S. Source: Archives of Dermatology. 2002 April; 138(4): 537-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939826&dopt=Abstract
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Methimazole-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis and lupus-like syndrome with a cutaneous feature of vesiculo-bullous systemic lupus erythematosus. Author(s): Thong HY, Chu CY, Chiu HC. Source: Acta Dermato-Venereologica. 2002; 82(3): 206-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353714&dopt=Abstract
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Methotrexate treatment for refractory subacute cutaneous lupus erythematosus. Author(s): Kuhn A, Specker C, Ruzicka T, Lehmann P. Source: Journal of the American Academy of Dermatology. 2002 April; 46(4): 600-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11907517&dopt=Abstract
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Methylprednisolone pulse therapy in Japanese children with severe lupus nephritis. Author(s): Tanaka H, Tateyama T, Waga S. Source: Pediatric Nephrology (Berlin, Germany). 2001 October; 16(10): 817-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11605789&dopt=Abstract
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Microchimerism in a female patient with systemic lupus erythematosus. Author(s): Johnson KL, McAlindon TE, Mulcahy E, Bianchi DW. Source: Arthritis and Rheumatism. 2001 September; 44(9): 2107-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11592373&dopt=Abstract
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Milia en plaque: a novel manifestation of chronic cutaneous lupus erythematosus. Author(s): Kouba DJ, Owens NM, Mimouni D, Klein W, Nousari CH. Source: The British Journal of Dermatology. 2003 August; 149(2): 424-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932260&dopt=Abstract
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Minimal change disease in systemic lupus erythematosus. Author(s): Dube GK, Markowitz GS, Radhakrishnan J, Appel GB, D'Agati VD. Source: Clinical Nephrology. 2002 February; 57(2): 120-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11863121&dopt=Abstract
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Minocycline-induced lupus and autoimmune hepatitis: family autoimmune disorders as possible risk factors. Author(s): Bachmeyer C, Cadranel JF. Source: Dermatology (Basel, Switzerland). 2002; 205(2): 185-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218241&dopt=Abstract
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Minocycline-induced lupus: a case series. Author(s): Porter D, Harrison A. Source: N Z Med J. 2003 April 4; 116(1171): U384. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740634&dopt=Abstract
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Minocycline-induced lupus-like syndrome. Author(s): Balestrero S, Ciambellotti A, Parodi A, Rebora A. Source: International Journal of Dermatology. 2001 July; 40(7): 474-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11679009&dopt=Abstract
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Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus. Author(s): Gergely P Jr, Grossman C, Niland B, Puskas F, Neupane H, Allam F, Banki K, Phillips PE, Perl A. Source: Arthritis and Rheumatism. 2002 January; 46(1): 175-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11817589&dopt=Abstract
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Mitral stenosis and regurgitation with systemic lupus erythematosus and antiphospholipid antibody syndrome. Author(s): Hasegawa R, Kitahara H, Watanabe K, Kuroda H, Amano J. Source: Jpn J Thorac Cardiovasc Surg. 2001 December; 49(12): 711-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808093&dopt=Abstract
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Mitral valve prolapse in systemic lupus erythematosus patients: clinical and immunological aspects. Author(s): Evangelopoulos ME, Alevizaki M, Toumanidis S, Sotou D, Evangelopoulos CD, Koutras DA, Stamatelopoulos SF, Mavrikakis M. Source: Lupus. 2003; 12(4): 308-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729055&dopt=Abstract
198 Lupus
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MIXCON-LA: a precise, sensitive and specific aPTT-based assay for detection of lupus anticoagulant. Author(s): Lindhoff-Last E, Humpich M, Schmitt J, Rodiger S, Seifried E, Bauersachs R. Source: Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2002 April; 8(2): 163-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121058&dopt=Abstract
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Mizoribine as an effective combined maintenance therapy with prednisolone in child-onset systemic lupus erythematosus. Author(s): Aihara Y, Miyamae T, Ito S, Kobayashi S, Imagawa T, Mori M, Ibe M, Mitsuda T, Yokota S. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 April; 44(2): 199-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11896887&dopt=Abstract
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Modulation of autoreactive responses of peripheral blood lymphocytes of patients with systemic lupus erythematosus by peptides based on human and murine antiDNA autoantibodies. Author(s): Sthoeger ZM, Dayan M, Tcherniack A, Green L, Toledo S, Segal R, Elkayam O, Mozes E. Source: Clinical and Experimental Immunology. 2003 February; 131(2): 385-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562403&dopt=Abstract
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Modulation of hormones in the treatment of lupus. Author(s): Walker SE. Source: Am J Manag Care. 2001 October; 7(16 Suppl): S486-9. Review. Erratum In: Am J Manag Care 2001 November; 7(11): 1030. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11680780&dopt=Abstract
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Molecular and clinical evidence of the role of estrogen in lupus. Author(s): Vidaver R. Source: Trends in Immunology. 2002 May; 23(5): 229-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102733&dopt=Abstract
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Monocyte and granulocyte phagocytosis of Escherichia coil particles in systemic lupus erythematosus is not reduced when compared to healthy controls. Author(s): Moosig F, Graf D, Knorr-Spahr A, Zeuner RA, Bottcher S, Schroder JO. Source: Lupus. 2003; 12(6): 490-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873054&dopt=Abstract
Studies 199
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Monocyte chemoattractant protein-1 expression in renal tissue is associated with monocyte recruitment and tubulo-interstitial lesions in patients with lupus nephritis. Author(s): Dai C, Liu Z, Zhou H, Li L. Source: Chin Med J (Engl). 2001 August; 114(8): 864-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11780369&dopt=Abstract
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Monocyte response to Th1 stimulation and effector function toward human mesangial cells are not impaired in patients with lupus nephritis. Author(s): Kuroiwa T, Schlimgen R, Illei GG, Boumpas DT. Source: Clinical Immunology (Orlando, Fla.). 2003 January; 106(1): 65-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584053&dopt=Abstract
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Mortality and causes of death in systemic lupus erythematosus. Author(s): Trager J, Ward MM. Source: Current Opinion in Rheumatology. 2001 September; 13(5): 345-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11604587&dopt=Abstract
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Mortality patterns in childhood lupus--10 years' experience in a developing country. Author(s): Singh S, Devidayal, Kumar L, Joshi K. Source: Clinical Rheumatology. 2002 November; 21(6): 462-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447628&dopt=Abstract
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Mortality patterns in Malaysian systemic lupus erythematosus patients. Author(s): Yeap SS, Chow SK, Manivasagar M, Veerapen K, Wang F. Source: Med J Malaysia. 2001 September; 56(3): 308-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732075&dopt=Abstract
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Multiple eruptive dermatofibromas in patients with systemic lupus erythematosus treated with prednisone. Author(s): Massone C, Parodi A, Virno G, Rebora A. Source: International Journal of Dermatology. 2002 May; 41(5): 279-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100703&dopt=Abstract
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Multiple minute parakeratotic keratoses of the hands in a patient with systemic lupus erythematosus. Author(s): Lin YC, Chiu HC, Chuan MT. Source: The British Journal of Dermatology. 2001 October; 145(4): 682-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11703310&dopt=Abstract
200 Lupus
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Multiple myeloma associated with systemic lupus erythematosus. Author(s): Vaiopoulos G, Konstantopoulos K, Mantzourani M, Kaklamanis P. Source: Leukemia & Lymphoma. 2003 February; 44(2): 373-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688362&dopt=Abstract
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Mutation of DNASE1 in people with systemic lupus erythematosus. Author(s): Yasutomo K, Horiuchi T, Kagami S, Tsukamoto H, Hashimura C, Urushihara M, Kuroda Y. Source: Nature Genetics. 2001 August; 28(4): 313-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11479590&dopt=Abstract
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Mycobacterium avium complex-associated hemophagocytic syndrome in systemic lupus erythematosus patient: report of one case. Author(s): Yang WK, Fu LS, Lan JL, Shen GH, Chou G, Tseng CF, Chi CS. Source: Lupus. 2003; 12(4): 312-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729056&dopt=Abstract
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Mycobacterium kansasii arthritis of the foot in a patient with systemic lupus erythematosus. Author(s): Nakamura T, Yamamura Y, Tsuruta T, Tomoda K, Sakaguchi M, Tsukano M. Source: Intern Med. 2001 October; 40(10): 1045-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11688832&dopt=Abstract
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Mycobacterium kansasii infection presenting as cellulitis in a patient with systemic lupus erythematosus. Author(s): Hsu PY, Yang YH, Hsiao CH, Lee PI, Chiang BL. Source: J Formos Med Assoc. 2002 August; 101(8): 581-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440090&dopt=Abstract
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Mycophenolate mofetil for systemic lupus erythematosus refractory to other immunosuppressive agents. Author(s): Karim MY, Alba P, Cuadrado MJ, Abbs IC, D'Cruz DP, Khamashta MA, Hughes GR. Source: Rheumatology (Oxford, England). 2002 August; 41(8): 876-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12154204&dopt=Abstract
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Mycophenolate mofetil for the treatment of cutaneous lupus erythematosus with smoldering systemic involvement. Author(s): Hanjani NM, Nousari CH. Source: Archives of Dermatology. 2002 December; 138(12): 1616-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472362&dopt=Abstract
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Mycophenolate mofetil in lupus glomerulonephritis. Author(s): Mok CC, Lai KN. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 September; 40(3): 447-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200794&dopt=Abstract
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Mycophenolate mofetil prevents a clinical relapse in patients with systemic lupus erythematosus at risk. Author(s): Bijl M, Horst G, Bootsma H, Limburg PC, Kallenberg CG. Source: Annals of the Rheumatic Diseases. 2003 June; 62(6): 534-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759290&dopt=Abstract
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Mycophenolate mofetil treatment of severe renal disease in pediatric onset systemic lupus erythematosus. Author(s): Buratti S, Szer IS, Spencer CH, Bartosh S, Reiff A. Source: The Journal of Rheumatology. 2001 September; 28(9): 2103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550982&dopt=Abstract
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Mycophenolate mofetil vs cyclophosphamide therapy for patients with diffuse proliferative lupus nephritis. Author(s): Hu W, Liu Z, Chen H, Tang Z, Wang Q, Shen K, Li L. Source: Chin Med J (Engl). 2002 May; 115(5): 705-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12133539&dopt=Abstract
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Myelitis as a presenting feature of systemic lupus erythromatosus. Author(s): Suralkar SS, Bichile LS, Sonawale AS, Rajyadhyaksha AG, Kothari C. Source: J Assoc Physicians India. 2003 January; 51: 62-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693458&dopt=Abstract
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Myocardial ischemia during emergency anesthesia in a patient with systemic lupus erythematosus resulting from undiagnosed antiphospholipid syndrome. Author(s): Ozaki M, Minami K, Shigematsu A. Source: Anesthesia and Analgesia. 2002 July; 95(1): 255. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088987&dopt=Abstract
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Myocarditis in systemic lupus erythematosus. Author(s): Wijetunga M, Rockson S. Source: The American Journal of Medicine. 2002 October 1; 113(5): 419-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401537&dopt=Abstract
202 Lupus
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Necrotizing ileitis caused by cytomegalovirus in patient with systemic lupus erythematosus: case report. Author(s): Vilaichone RK, Mahachai V, Eiam-Ong S, Kullavanuaya P, Wisedopas N, Bhattarakosol P. Source: J Med Assoc Thai. 2001 June; 84 Suppl 1: S469-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11529377&dopt=Abstract
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Necrotizing pneumonia caused by Streptococcus pneumoniae in a child with systemic lupus erythematosus. Author(s): Chiu WJ, Kao HT, Huang JL. Source: Acta Paediatr Taiwan. 2002 September-October; 43(5): 291-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607488&dopt=Abstract
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Neonatal lupus erythematosus associated with maternal mixed connective tissue disease. Author(s): Fujiwaki T, Urashima R, Urushidani Y, Takahashi T, Ishioka C. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 April; 45(2): 210-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709154&dopt=Abstract
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Neonatal lupus erythematosus in association with anti-RNP antibody: a case report. Author(s): Su CT, Huang CB, Chung MY. Source: American Journal of Perinatology. 2001 December; 18(8): 421-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11733856&dopt=Abstract
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Neonatal lupus erythematosus mimicking langerhans cell histiocytosis. Author(s): Scheker LE, Kasteler JS, Callen JP. Source: Pediatric Dermatology. 2003 March-April; 20(2): 164-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12657018&dopt=Abstract
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Neonatal lupus erythematosus with recurrent pancytopenia: a case report. Author(s): Wang LJ, Yang YH, Lin MI, Chiang BL, Mu SC. Source: J Microbiol Immunol Infect. 2002 December; 35(4): 262-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12542254&dopt=Abstract
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Neonatal lupus erythematosus. Author(s): Burch JM, Lee LA, Weston WL. Source: Dermatology Nursing / Dermatology Nurses' Association. 2002 June; 14(3): 15760. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099063&dopt=Abstract
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Neonatal lupus erythematosus: clinical manifestations and management. Author(s): Chunharas A, Nuntnarumit P, Hongeng S, Chaunsumrit A. Source: J Med Assoc Thai. 2002 November; 85 Suppl 4: S1302-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12549810&dopt=Abstract
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Neonatal lupus erythematosus: factors which may lead to clinical disease in the foetus even in the absence of disease in the mother. Author(s): Kim J, Smith KJ, Skelton H. Source: Clinical and Experimental Dermatology. 2001 July; 26(5): 423-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11488832&dopt=Abstract
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Neonatal lupus manifests as isolated neutropenia and mildly abnormal liver functions. Author(s): Kanagasegar S, Cimaz R, Kurien BT, Brucato A, Scofield RH. Source: The Journal of Rheumatology. 2002 January; 29(1): 187-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11824959&dopt=Abstract
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Neonatal lupus. Author(s): Brucato A, Cimaz R, Stramba-Badiale M. Source: Clinical Reviews in Allergy & Immunology. 2002 December; 23(3): 279-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12402413&dopt=Abstract
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Neonatal lupus: clinical features, therapy, and pathogenesis. Author(s): Lee LA. Source: Curr Rheumatol Rep. 2001 October; 3(5): 391-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564370&dopt=Abstract
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Neonatal lupus: review of proposed pathogenesis and clinical data from the US-based Research Registry for Neonatal Lupus. Author(s): Buyon JP, Clancy RM. Source: Autoimmunity. 2003 February; 36(1): 41-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765470&dopt=Abstract
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Nerve growth factor in serum of children with systemic lupus erythematosus is correlated with disease activity. Author(s): Aalto K, Korhonen L, Lahdenne P, Pelkonen P, Lindholm D. Source: Cytokine. 2002 November 7; 20(3): 136-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453472&dopt=Abstract
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Neuromyelitis optica (Devic's syndrome) in systemic lupus erythematosus: a case report. Author(s): Gibbs AN, Moroney J, Foley-Nolan D, O'Connell PG. Source: Rheumatology (Oxford, England). 2002 April; 41(4): 470-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961183&dopt=Abstract
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Neuro-ophthalmological manifestations of systemic lupus erythematosus in Asian patients. Author(s): Teoh SC, Yap EY, Au Eong KG. Source: Clinical & Experimental Ophthalmology. 2001 August; 29(4): 213-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11545417&dopt=Abstract
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Neuropsychiatric involvement in systemic lupus erythematosus. Author(s): Hermosillo-Romo D, Brey RL. Source: Curr Rheumatol Rep. 2002 August; 4(4): 337-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126586&dopt=Abstract
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Neuropsychiatric lupus favourable response to low dose i.v. cyclophosphamide and prednisolone (pilot study). Author(s): Stojanovich L, Stojanovich R, Kostich V, Dzjolich E. Source: Lupus. 2003; 12(1): 3-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587819&dopt=Abstract
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Neuropsychiatric lupus: nomenclature, classification, criteria, and other confusional states. Author(s): Ruggieri AP. Source: Arthritis and Rheumatism. 2001 October; 45(5): 406-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11642638&dopt=Abstract
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Neuropsychiatric manifestations in systemic lupus erythematosus: prevalence and association with antiphospholipid antibodies. Author(s): Sanna G, Bertolaccini ML, Cuadrado MJ, Laing H, Khamashta MA, Mathieu A, Hughes GR. Source: The Journal of Rheumatology. 2003 May; 30(5): 985-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734893&dopt=Abstract
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Neuropsychiatric manifestations in Thai patients with systemic lupus erythematosus. Author(s): Kasitanon N, Louthrenoo W, Piyasirisilp S, Sukitawu W, Wichainun R. Source: Asian Pac J Allergy Immunol. 2002 September; 20(3): 179-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587842&dopt=Abstract
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Neuropsychiatric syndromes in lupus: prevalence using standardized definitions. Author(s): Brey RL, Holliday SL, Saklad AR, Navarrete MG, Hermosillo-Romo D, Stallworth CL, Valdez CR, Escalante A, del Rincon I, Gronseth G, Rhine CB, Padilla P, McGlasson D. Source: Neurology. 2002 April 23; 58(8): 1214-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11971089&dopt=Abstract
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Neuropsychiatric systemic lupus erythematosus presenting as amyotrophic lateral sclerosis. Author(s): Maldonado ME, Williams RC Jr, Adair JC, Hart BL, Gregg L, Sibbitt WL Jr. Source: The Journal of Rheumatology. 2002 March; 29(3): 633-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908583&dopt=Abstract
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Neuropsychiatric systemic lupus erythematosus, age, and the neurodevelopmental model: evidence in support of the Weinberger hypothesis. Author(s): Mack AH, Fricchione G, Rogers MP. Source: Comprehensive Psychiatry. 2002 March-April; 43(2): 135-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893992&dopt=Abstract
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Neuropsychological function in systemic lupus erythematosus: a five-year longitudinal study. Author(s): Waterloo K, Omdal R, Husby G, Mellgren SI. Source: Rheumatology (Oxford, England). 2002 April; 41(4): 411-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961171&dopt=Abstract
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Neuropsychological functioning and its relationship to antiphospholipid antibodies in patients with systemic lupus erythematosus. Author(s): Leritz E, Brandt J, Minor M, Reis-Jensen F, Petri M. Source: J Clin Exp Neuropsychol. 2002 June; 24(4): 527-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187465&dopt=Abstract
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Neutrophils from systemic lupus erythematosus patients demonstrate increased nuclear DNA damage. Author(s): McConnell JR, Crockard AD, Cairns AP, Bell AL. Source: Clin Exp Rheumatol. 2002 September-October; 20(5): 653-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412196&dopt=Abstract
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New insights into the pathogenesis of systemic lupus erythematosus (SLE): the role of apoptosis. Author(s): Bijl M, Limburg PC, Kallenberg CG. Source: The Netherlands Journal of Medicine. 2001 August; 59(2): 66-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11476915&dopt=Abstract
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New onset systemic lupus erythematosus in a patient receiving etanercept for rheumatoid arthritis. Author(s): Cairns AP, Duncan MK, Hinder AE, Taggart AJ. Source: Annals of the Rheumatic Diseases. 2002 November; 61(11): 1031-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12379532&dopt=Abstract
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New onset systemic lupus erythematosus with pheochromocytoma. Author(s): Lin AT, Min Y, Clements PJ, Morris R, Shayestehfar B, Mankin L, Wong AL. Source: The Journal of Rheumatology. 2002 June; 29(6): 1334-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064856&dopt=Abstract
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New therapies in systemic lupus erythematosus. Author(s): Solsky MA, Wallace DJ. Source: Best Practice & Research. Clinical Rheumatology. 2002 April; 16(2): 293-312. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041955&dopt=Abstract
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Newer drugs for the treatment of lupus nephritis. Author(s): Kuiper-Geertsma DG, Derksen RH. Source: Drugs. 2003; 63(2): 167-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515564&dopt=Abstract
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Nitrendipine-induced subacute cutaneous lupus erythematosus. Author(s): Marzano AV, Borghi A, Mercogliano M, Facchetti M, Caputo R. Source: Eur J Dermatol. 2003 March-April; 13(2): 213-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695145&dopt=Abstract
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Nitric oxide synthase 2 promoter polymorphisms and systemic lupus erythematosus in african-americans. Author(s): Oates JC, Levesque MC, Hobbs MR, Smith EG, Molano ID, Page GP, Hill BS, Weinberg JB, Cooper GS, Gilkeson GS. Source: The Journal of Rheumatology. 2003 January; 30(1): 60-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508391&dopt=Abstract
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No association of vitamin D receptor gene start codon fok 1 polymorphisms in Chinese patients with systemic lupus erythematosus. Author(s): Huang CM, Wu MC, Wu JY, Tsai FJ. Source: The Journal of Rheumatology. 2002 June; 29(6): 1211-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064837&dopt=Abstract
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No lupus nephritis in the absence of antiC1q autoantibodies? Author(s): Fremeaux-Bacchi V, Noel LH, Schifferli JA. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2002 December; 17(12): 2041-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454207&dopt=Abstract
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No short-term immunological effects of Pneumococcus vaccination in patients with systemic lupus erythematosus. Author(s): Tarjan P, Sipka S, Marodi L, Nemes E, Lakos G, Gyimesi E, Kiss E, Ujj G, Szegedi G. Source: Scandinavian Journal of Rheumatology. 2002; 31(4): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369652&dopt=Abstract
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Nodular invasive tracheobronchitis due to Aspergillus in a patient with systemic lupus erythematosus. Author(s): Angelotti T, Krishna G, Scott J, Berry G, Weinacker A. Source: Lupus. 2002; 11(5): 325-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090570&dopt=Abstract
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Nondissecting aneurysm of the thoracic aorta with arteritis in systemic lupus erythematosus. Author(s): Takagi H, Mori Y, Iwata H, Kimura M, Itokazu M, Shimokawa K, Hirose H. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2002 April; 35(4): 801-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932683&dopt=Abstract
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Non-fatal septicaemic Nocardia asteroides in a girl with systemic lupus erythematosus. Author(s): Vachvanichsanong P, Pruekprasert P, Dissaneewate P. Source: European Journal of Pediatrics. 2002 April; 161(4): 222-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014392&dopt=Abstract
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Non-Hodgkin's lymphoma in patients with systemic lupus erythematosus. Author(s): Papadaki HA, Xylouri I, Katrinakis G, Foudoulakis A, Kritikos HD, Stathopoulos EN, Boumpas DT, Eliopoulos GD. Source: Leukemia & Lymphoma. 2003 February; 44(2): 275-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688345&dopt=Abstract
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Non-Hodgkin's lymphoma in patients with systemic lupus erythematosus: 2 case reports. Author(s): Ferri M, Mar C, Bhatia RS. Source: Canadian Association of Radiologists Journal = Journal L'association Canadienne Des Radiologistes. 2002 April; 53(2): 81-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975105&dopt=Abstract
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Non-invasive cardiac evaluation in patients with systemic lupus erythematosus. Author(s): Wranicz JK, Cygankiewicz I, Zielinska M, Wozniacka A, Sysa-Jedrzejowska A. Source: J Med. 2001; 32(3-4): 195-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563818&dopt=Abstract
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Nonlupus nephritides in patients with systemic lupus erythematosus: a comprehensive clinicopathologic study and review of the literature. Author(s): Baranowska-Daca E, Choi YJ, Barrios R, Nassar G, Suki WN, Truong LD. Source: Human Pathology. 2001 October; 32(10): 1125-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11679948&dopt=Abstract
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Novel approaches in the treatment of lupus nephritis. Author(s): Illei GG, Czirjak L. Source: Expert Opinion on Investigational Drugs. 2001 June; 10(6): 1117-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772239&dopt=Abstract
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Novel molecular targets for systemic lupus erythematosus. Author(s): Marino M, Rossi M, Ruvo M, Fassina G. Source: Current Drug Targets. 2002 June; 3(3): 223-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041736&dopt=Abstract
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Novel therapeutic agents for systemic lupus erythematosus. Author(s): Gescuk BD, Davis JC Jr. Source: Current Opinion in Rheumatology. 2002 September; 14(5): 515-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192247&dopt=Abstract
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Novel therapies in the treatment of systemic lupus erythematosus. Author(s): Dequet CR, Wallace DJ. Source: Curr Opin Investig Drugs. 2001 August; 2(8): 1045-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892912&dopt=Abstract
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Objective evidence of abnormal regional cerebral blood flow in patients with systemic lupus erythematosus on Tc-99m ECD brain SPECT. Author(s): Huang WS, Chiu PY, Tsai CH, Kao A, Lee CC. Source: Rheumatology International. 2002 September; 22(5): 178-81. Epub 2002 July 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215861&dopt=Abstract
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Occupational exposure to crystalline silica and risk of systemic lupus erythematosus: a population-based, case-control study in the southeastern United States. Author(s): Parks CG, Cooper GS, Nylander-French LA, Sanderson WT, Dement JM, Cohen PL, Dooley MA, Treadwell EL, St Clair EW, Gilkeson GS, Hoppin JA, Savitz DA. Source: Arthritis and Rheumatism. 2002 July; 46(7): 1840-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124868&dopt=Abstract
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Occurrence of thrombotic thrombocytopenic purpura in a systemic lupus erythematosus patient with antiphospholipid antibodies in association with a decreased activity of von Willebrand factor-cleaving protease. Author(s): Matsuda J, Sanaka T, Gohchi K, Matsui K, Uchida S, Matsumoto M, Fujimura Y. Source: Lupus. 2002; 11(7): 463-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195790&dopt=Abstract
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Oculomotor palsy in six patients with systemic lupus erythematosus. A possible role of antiphospholipid syndrome. Author(s): Genevay S, Hayem G, Hamza S, Palazzo E, Meyer O, Kahn MF. Source: Lupus. 2002; 11(5): 313-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12090567&dopt=Abstract
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Of ethnicity, race and lupus. Author(s): Alarcon GS. Source: Lupus. 2001; 10(9): 594-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11678445&dopt=Abstract
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Optic neuritis and retinal vasculitis as primary manifestations of systemic lupus erythematosus. Author(s): Barkeh HJ, Muhaya M. Source: Med J Malaysia. 2002 December; 57(4): 490-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12733176&dopt=Abstract
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Optic neuropathy and chiasmopathy in the diagnosis of systemic lupus erythematosus. Author(s): Siatkowski RM, Scott IU, Verm AM, Warn AA, Farris BK, Strominger MB, Sklar EM. Source: Journal of Neuro-Ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society. 2001 September; 21(3): 193-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11725184&dopt=Abstract
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Orderly pattern of development of the autoantibody response in (New Zealand White x BXSB)F1 lupus mice: characterization of target antigens and antigen spreading by two-dimensional gel electrophoresis and mass spectrometry. Author(s): Thebault S, Gilbert D, Hubert M, Drouot L, Machour N, Lange C, Charlionet R, Tron F. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 October 1; 169(7): 4046-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12244208&dopt=Abstract
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Organ manifestations influence differently the responsiveness of 2 lupus disease activity measures, according to patients' or physicians' evaluations of recent lupus activity. Author(s): Chang ER, Abrahamowicz M, Ferland D, Fortin PR. Source: The Journal of Rheumatology. 2002 November; 29(11): 2350-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415591&dopt=Abstract
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Orthopaedic manifestations of systemic lupus erythematosus. Author(s): Egol KA, Jazrawi LM, DeWal H, Su E, Leslie MP, Di Cesare PE. Source: Bull Hosp Jt Dis. 2001; 60(1): 29-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11759575&dopt=Abstract
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Osteonecrosis in patients with systemic lupus erythematosus develops very early after starting high dose corticosteroid treatment. Author(s): Oinuma K, Harada Y, Nawata Y, Takabayashi K, Abe I, Kamikawa K, Moriya H. Source: Annals of the Rheumatic Diseases. 2001 December; 60(12): 1145-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709458&dopt=Abstract
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Osteoporosis screening in systemic lupus erythematosus: impact of disease duration and organ damage. Author(s): Becker A, Fischer R, Scherbaum WA, Schneider M. Source: Lupus. 2001; 10(11): 809-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789491&dopt=Abstract
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Outcome after transplantation of young patients with systemic lupus erythematosus: a report of the North American pediatric renal transplant cooperative study. Author(s): Bartosh SM, Fine RN, Sullivan EK. Source: Transplantation. 2001 September 15; 72(5): 973-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11571477&dopt=Abstract
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Outcome and prognostic indicators of diffuse proliferative lupus glomerulonephritis treated with sequential oral cyclophosphamide and azathioprine. Author(s): Mok CC, Ho CT, Chan KW, Lau CS, Wong RW. Source: Arthritis and Rheumatism. 2002 April; 46(4): 1003-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953978&dopt=Abstract
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Outcome of a cohort of 300 patients with systemic lupus erythematosus attending a dedicated clinic for over two decades. Author(s): Moss KE, Ioannou Y, Sultan SM, Haq I, Isenberg DA. Source: Annals of the Rheumatic Diseases. 2002 May; 61(5): 409-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959764&dopt=Abstract
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Outcome of neuropsychiatric systemic lupus erythematosus within a defined Swedish population: increased morbidity but low mortality. Author(s): Jonsen A, Bengtsson AA, Nived O, Ryberg B, Sturfelt G. Source: Rheumatology (Oxford, England). 2002 November; 41(11): 1308-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422005&dopt=Abstract
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Outcome of pregnancy in Asian women with systemic lupus erythematosus: experience of a single perinatal centre in Singapore. Author(s): Tan LK, Tan HK, Lee CT, Tan AS. Source: Ann Acad Med Singapore. 2002 May; 31(3): 290-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12061288&dopt=Abstract
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Outcome of relapse in lupus nephritis: roles of reversal of renal fibrosis and response of inflammation to therapy. Author(s): Hill GS, Delahousse M, Nochy D, Thervet E, Vrtovsnik F, Remy P, Glotz D, Bariety J. Source: Kidney International. 2002 June; 61(6): 2176-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028458&dopt=Abstract
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Outcomes of symptomatic osteonecrosis in 95 patients with systemic lupus erythematosus. Author(s): Gladman DD, Chaudhry-Ahluwalia V, Ibanez D, Bogoch E, Urowitz MB. Source: The Journal of Rheumatology. 2001 October; 28(10): 2226-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11669161&dopt=Abstract
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Oxidants, anti-oxidants, essential fatty acids, eicosanoids, cytokines, gene/oncogene expression and apoptosis in systemic lupus erythematosus. Author(s): Das UN. Source: J Assoc Physicians India. 1998 July; 46(7): 630-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12152850&dopt=Abstract
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Pancarditis as initial presentation of systemic lupus erythematosus. Author(s): Chockalingam A, Prabhakar D, Gnanavelu G, Chockalingam V. Source: International Journal of Cardiology. 2003 January; 87(1): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468063&dopt=Abstract
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Pancreatitis leading to thrombotic thrombocytopenic purpura in systemic lupus erythematosus: a case report and review of literature. Author(s): Singh R, Saunders B, Scopelitis E. Source: Lupus. 2003; 12(2): 136-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630759&dopt=Abstract
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Papulonodular mucinosis associated with subacute cutaneous lupus erythematosus. Author(s): Sonntag M, Lehmann P, Megahed M, Ruzicka T, Kuhn A. Source: Dermatology (Basel, Switzerland). 2003; 206(4): 326-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771474&dopt=Abstract
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Parotid calcification in systemic lupus erythematosis. Author(s): Hopkins C, Kanegaonkar R, Chevretton EB. Source: The Journal of Laryngology and Otology. 2002 October; 116(10): 859-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12437847&dopt=Abstract
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Pathogenesis of systemic lupus erythematosus. Author(s): Mok CC, Lau CS. Source: Journal of Clinical Pathology. 2003 July; 56(7): 481-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835292&dopt=Abstract
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Pathological lymphocyte activation by defective clearance of self-ligands in systemic lupus erythematosus. Author(s): Yasutomo K. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 214-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595613&dopt=Abstract
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Patient preferences for treatment of lupus nephritis. Author(s): Fraenkel L, Bogardus S, Concato J. Source: Arthritis and Rheumatism. 2002 Aug15; 47(4): 421-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209490&dopt=Abstract
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Pemphigus vulgaris and systemic lupus erythematosus in a 46-y-old man. Author(s): Hidalgo-Tenorio C, Sabio-Sanchez JM, Tercedor-Sanchez J, Leon-Ruiz L, Perez-Alvarez F, Jimenez-Alonso J. Source: Lupus. 2001; 10(11): 824-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789495&dopt=Abstract
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Peptide mimics of a major lupus epitope of SmB/B'. Author(s): Kaufman KM, Kirby MY, Harley JB, James JA. Source: Annals of the New York Academy of Sciences. 2003 April; 987: 215-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727642&dopt=Abstract
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Periorbital oedema and erythema as a manifestation of discoid lupus erythematosus. Author(s): Braun RP, French LE, Massouye I, Saurat JH. Source: Dermatology (Basel, Switzerland). 2002; 205(2): 194-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218246&dopt=Abstract
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Peripheral aneurysm rupture in a patient with inactive systemic lupus erythematosus. Author(s): Engelke C, Mohan AR, Sabharwal T, Reidy JF. Source: European Radiology. 2002 December; 12(12): 2895-7. Epub 2002 April 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439567&dopt=Abstract
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Peripheral neuropathy in pediatric systemic lupus erythematosus. Author(s): Ryan M. Source: Pediatric Neurology. 2003 March; 28(3): 236; Author Reply 236. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770683&dopt=Abstract
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Peripheral neuropathy in systemic lupus erythematosus: pathomorphological features and distribution pattern of matrix metalloproteinases. Author(s): Mawrin C, Brunn A, Rocken C, Schroder JM. Source: Acta Neuropathologica. 2003 April; 105(4): 365-72. Epub 2002 December 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624790&dopt=Abstract
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Persistent mitochondrial hyperpolarization, increased reactive oxygen intermediate production, and cytoplasmic alkalinization characterize altered IL-10 signaling in patients with systemic lupus erythematosus. Author(s): Gergely P Jr, Niland B, Gonchoroff N, Pullmann R Jr, Phillips PE, Perl A. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 July 15; 169(2): 1092-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097418&dopt=Abstract
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Persistent pneumonia in a boy with systemic lupus erythematosus. Author(s): Lee AY, Ogershok PR, Weisse ME. Source: Clinical Pediatrics. 2002 July-August; 41(6): 443-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12166798&dopt=Abstract
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Persistent scarring, atrophy, and dyspigmentation in a preteen girl with neonatal lupus erythematosus. Author(s): High WA, Costner MI. Source: Journal of the American Academy of Dermatology. 2003 April; 48(4): 626-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664034&dopt=Abstract
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Perturbations of peripheral B lymphocyte homoeostasis in children with systemic lupus erythematosus. Author(s): Odendahl M, Keitzer R, Wahn U, Hiepe F, Radbruch A, Dorner T, Bunikowski R. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 851-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922958&dopt=Abstract
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Photosensitivity in patients with lupus erythematosus: a clinical and photobiological study of 100 patients using a prolonged phototest protocol. Author(s): Sanders CJ, Van Weelden H, Kazzaz GA, Sigurdsson V, Toonstra J, Bruijnzeel-Koomen CA. Source: The British Journal of Dermatology. 2003 July; 149(1): 131-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890206&dopt=Abstract
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Platelet autoantibodies and lupus-associated thrombocytopenia. Author(s): Michel M, Lee K, Piette JC, Fromont P, Schaeffer A, Bierling P, Godeau B. Source: British Journal of Haematology. 2002 November; 119(2): 354-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406068&dopt=Abstract
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Pneumococcal sepsis in a girl with systemic lupus erythematosus. Author(s): La Spina M, Russo G. Source: British Journal of Haematology. 2003 July; 122(2): 172. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846883&dopt=Abstract
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Polyarteritis nodosa developing after discoid lupus erythematosus. Author(s): Letellier E, Longhurst H, Diaz-Cano SJ, D'Cruz D. Source: Clin Exp Rheumatol. 2001 November-December; 19(6): 738-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791651&dopt=Abstract
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Polymerase chain reaction based C4AQ0 and C4BQ0 genotyping: association with systemic lupus erythematosus in southwest Han Chinese. Author(s): Man XY, Luo HR, Li XP, Yao YG, Mao CZ, Zhang YP. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 71-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480675&dopt=Abstract
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Polymorphic light eruption and the HLA DRB1*0301 extended haplotype are independent risk factors for cutaneous lupus erythematosus. Author(s): Millard TP, Kondeatis E, Vaughan RW, Lewis CM, Khamashta MA, Hughes GR, Hawk JL, McGregor JM. Source: Lupus. 2001; 10(7): 473-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480844&dopt=Abstract
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Polymorphisms of human CD19 gene: possible association with susceptibility to systemic lupus erythematosus in Japanese. Author(s): Kuroki K, Tsuchiya N, Tsao BP, Grossman JM, Fukazawa T, Hagiwara K, Kano H, Takazoe M, Iwata T, Hashimoto H, Tokunaga K. Source: Genes and Immunity. 2002 October; 3 Suppl 1: S21-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215898&dopt=Abstract
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Polymorphisms of the interleukin-4 gene in chinese patients with systemic lupus erythematosus in Taiwan. Author(s): Wu MC, Huang CM, Tsai JJ, Chen HY, Tsai FJ. Source: Lupus. 2003; 12(1): 21-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587822&dopt=Abstract
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Polyradiculopathy in a patient of systemic lupus erythematosus. Author(s): Bharadwaj A, Shenoy D, Aggarwal A. Source: J Assoc Physicians India. 2003 March; 51: 304-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839359&dopt=Abstract
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Possible phototoxicity with subsequent progression to discoid lupus following pantoprazole administration. Author(s): Correia O, Lomba Viana H, Azevedo R, Delgado L, Polonia J. Source: Clinical and Experimental Dermatology. 2001 July; 26(5): 455-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11488838&dopt=Abstract
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Postoperative pneumococcal cellulitis in systemic lupus erythematosus. Author(s): Page KR, Karakousis PC, Maslow JN. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(2): 141-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693569&dopt=Abstract
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Powerful morphometric indicator of prognosis in lupus nephritis. Author(s): Howie AJ, Turhan N, Adu D. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 June; 96(6): 411-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788959&dopt=Abstract
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Prediction of lupus nephritis in patients with systemic lupus erythematosus using artificial neural networks. Author(s): Rajimehr R, Farsiu S, Kouhsari LM, Bidari A, Lucas C, Yousefian S, Bahrami F. Source: Lupus. 2002; 11(8): 485-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220102&dopt=Abstract
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Predictors of poor renal outcome in patients with lupus nephritis treated with combined pulses of cyclophosphamide and methylprednisolone. Author(s): Cortes-Hernandez J, Ordi-Ros J, Labrador M, Segarra A, Tovar JL, Balada E, Vilardell-Tarres M. Source: Lupus. 2003; 12(4): 287-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729052&dopt=Abstract
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Predictors of sustained amenorrhea from pulsed intravenous cyclophosphamide in premenopausal women with systemic lupus erythematosus. Author(s): Ioannidis JP, Katsifis GE, Tzioufas AG, Moutsopoulos HM. Source: The Journal of Rheumatology. 2002 October; 29(10): 2129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375322&dopt=Abstract
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Predominance of IgG1 and IgG3 subclasses of autoantibodies to neutrophil cytoplasmic antigens in patients with systemic lupus erythematosus. Author(s): Manolova I, Dancheva M, Halacheva K. Source: Rheumatology International. 2002 April; 21(6): 227-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036209&dopt=Abstract
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Preferential expression of B7.2 (CD86), but not B7.1 (CD80), on B cells induced by CD40/CD40L interaction is essential for anti-DNA autoantibody production in patients with systemic lupus erythematosus. Author(s): Nagafuchi H, Shimoyama Y, Kashiwakura J, Takeno M, Sakane T, Suzuki N. Source: Clin Exp Rheumatol. 2003 January-February; 21(1): 71-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673892&dopt=Abstract
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Pregnancy in lupus nephritis. Author(s): Moroni G, Quaglini S, Banfi G, Caloni M, Finazzi S, Ambroso G, Como G, Ponticelli C. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 October; 40(4): 713-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12324905&dopt=Abstract
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Pregnancy outcome in systemic lupus erythematosus: good news for the new millennium. Author(s): Cervera R, Font J, Carmona F, Balasch J. Source: Autoimmunity Reviews. 2002 December; 1(6): 354-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848991&dopt=Abstract
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Pregnancy outcomes in female renal recipients: a comparison of systemic lupus erythematosus with other diagnoses. Author(s): McGrory CH, McCloskey LJ, DeHoratius RJ, Dunn SR, Moritz MJ, Armenti VT. Source: American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2003 January; 3(1): 35-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492708&dopt=Abstract
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Premature coronary artery disease in systemic lupus erythematosus with extensive reocclusion following coronary artery bypass surgery. Author(s): D Agate DJ, Kokolis S, Belilos E, Carsons S, Andrieni J, Argyros T, Glasser LA, Dangas G. Source: J Invasive Cardiol. 2003 March; 15(3): 157-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12612393&dopt=Abstract
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Presence of cutaneous interferon-alpha producing cells in patients with systemic lupus erythematosus. Author(s): Blomberg S, Eloranta ML, Cederblad B, Nordlin K, Alm GV, Ronnblom L. Source: Lupus. 2001; 10(7): 484-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480846&dopt=Abstract
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Prevalence of factors influencing cancer risk in women with lupus: social habits, reproductive issues, and obesity. Author(s): Bernatsky S, Boivin JF, Joseph L, St Pierre Y, Moore A, Rajan R, Clarke A. Source: The Journal of Rheumatology. 2002 December; 29(12): 2551-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465150&dopt=Abstract
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Prevalence of lupus anticoagulant in multiparous women in Benin City, Nigeria. Author(s): Awodu OA, Ejele OA, Shokunbi WA, Enosolease ME. Source: Niger Postgrad Med J. 2003 March; 10(1): 19-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812147&dopt=Abstract
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Prevalence of T cell receptor zeta chain deficiency in systemic lupus erythematosus. Author(s): Nambiar MP, Mitchell JP, Ceruti RP, Malloy MA, Tsokos GC. Source: Lupus. 2003; 12(1): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587826&dopt=Abstract
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Prevalence, patterns of disease and outcome in patients with systemic lupus erythematosus who develop severe haematological problems. Author(s): Sultan SM, Begum S, Isenberg DA. Source: Rheumatology (Oxford, England). 2003 February; 42(2): 230-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595615&dopt=Abstract
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Primary sclerosing cholangitis associated with lupus nephritis: a rare association. Author(s): Kadokawa Y, Omagari K, Matsuo I, Otsu Y, Yamamoto U, Nishino T, Ohba K, Miyazaki M, Harada T, Taguchi T, Kohno S. Source: Digestive Diseases and Sciences. 2003 May; 48(5): 911-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772788&dopt=Abstract
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Production of thromboxane A2 and prostaglandin i2 affected by interaction of heat aggregated IgG, endothelial cells, and platelets in lupus nephritis. Author(s): Kaneko N, Masuyama J, Nara H, Hirata D, Iwamoto M, Okazaki H, Minota S, Yoshio T. Source: The Journal of Rheumatology. 2002 October; 29(10): 2106-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375319&dopt=Abstract
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Profiles of the acute-phase reactants C-reactive protein and ferritin related to the disease course of patients with systemic lupus erythematosus. Author(s): Hesselink DA, Aarden LA, Swaak AJ. Source: Scandinavian Journal of Rheumatology. 2003; 32(3): 151-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892251&dopt=Abstract
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Progressive multifocal leucoencephalopathy isolated to the posterior fossa in a patient with systemic lupus erythematosus. Author(s): White RP, Abraham S, Singhal S, Manji H, Clarke CR. Source: Rheumatology (Oxford, England). 2002 July; 41(7): 826-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096236&dopt=Abstract
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Proinflammatory interferon-gamma--inducing monokines (interleukin-12, interleukin-18, interleukin-15)--serum profile in patients with systemic lupus erythematosus. Author(s): Robak E, Robak T, Wozniacka A, Zak-Prelich M, Sysa-Jedrzejowska A, Stepien H. Source: Eur Cytokine Netw. 2002 July-September; 13(3): 364-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12231481&dopt=Abstract
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Prolactin and prolactin receptor gene polymorphisms in multiple sclerosis and systemic lupus erythematosus. Author(s): Mellai M, Giordano M, D'Alfonso S, Marchini M, Scorza R, Giovanna Danieli M, Leone M, Ferro I, Liguori M, Trojano M, Ballerini C, Massacesi L, Cannoni S, Bomprezzi R, Momigliano-Richiardi P. Source: Human Immunology. 2003 February; 64(2): 274-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559630&dopt=Abstract
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Propylthiouracil-induced lupus-like syndrome developing in a Graves' patient with a sibling with systemic lupus erythematosus. Author(s): Yamada A, Sato K, Hara M, Tochimoto A, Takagi S, Hizuka N, Takano K. Source: Intern Med. 2002 December; 41(12): 1204-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521217&dopt=Abstract
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Protein losing enteropathy in systemic lupus erythematosus: role of diet and octreotide. Author(s): Ossandon A, Bombardieri M, Coari G, Graziani G, Valesini G. Source: Lupus. 2002; 11(7): 465-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195791&dopt=Abstract
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Prothrombin binds to the surface of apoptotic, but not viable, cells and serves as a target of lupus anticoagulant autoantibodies. Author(s): D'Agnillo P, Levine JS, Subang R, Rauch J. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 March 15; 170(6): 3408-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626602&dopt=Abstract
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Proximal white subungual onychomycosis caused by Microsporum canis in systemic lupus erythematosus. Author(s): Tlacuilo-Parra A, Guevara-Gutierrez E, Mayorga J, Salazar-Paramo M. Source: Rheumatology International. 2002 April; 21(6): 250-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036214&dopt=Abstract
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Pseudohypoparathyroidism with systemic lupus erythematosus. Author(s): Somasundaram LS, Sankaranarayanan R. Source: J Assoc Physicians India. 2003 January; 51: 64-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693459&dopt=Abstract
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Pseudotumour cerebri presentation of systemic lupus erythematosus: more than an association. Author(s): Sbeiti S, Kayed DM, Majuri H. Source: Rheumatology (Oxford, England). 2003 June; 42(6): 808-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771445&dopt=Abstract
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Psychological profiles and health status in Japanese female patients with systemic lupus erythematosus: the Miyagi Lupus Collaborative Study. Author(s): Minami Y, Sasaki T, Arai Y, Hosokawa T, Hisamichi S. Source: J Epidemiol. 2002 March; 12(2): 55-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12033529&dopt=Abstract
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Pulmonary alveolar microlithiasis after Varicella zoster infection in a patient presenting with antiphospholipid syndrome and discoid lupus. Author(s): Yilmaz MI, Koc B, Kantarcioglu M, Akinci SB, Ayta H, Bulucu F, Bal S. Source: Rheumatology International. 2002 September; 22(5): 213-5. Epub 2002 July 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12215869&dopt=Abstract
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Pure red cell aplasia in a Sjogren's syndrome/lupus erythematosus overlap patient. Author(s): Mavragani CP, Vlachaki E, Voulgarelis M. Source: American Journal of Hematology. 2003 April; 72(4): 259-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12666137&dopt=Abstract
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Pyloric stenosis in a patient with systemic lupus erythematosus. Author(s): Takano H, Inoue K, Katada K, Yoshikawa T. Source: Endoscopy. 2002 October; 34(10): 846. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12244516&dopt=Abstract
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Pyoderma gangrenosum in a patient with bullous systemic lupus erythematosus. Author(s): Sakamoto T, Hashimoto T, Furukawa F. Source: Eur J Dermatol. 2002 September-October; 12(5): 485-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370142&dopt=Abstract
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Quantification of lupus anticoagulants in clinical samples using anti-beta2GP1 and anti-prothrombin monoclonal antibodies. Author(s): Le Querrec A, Arnout J, Arnoux D, Borg JY, Caron C, Darnige L, Delahousse B, Reber G, Sie P. Source: Thrombosis and Haemostasis. 2001 August; 86(2): 584-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522007&dopt=Abstract
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Quantitative analysis of interstitial mast cells in lupus and non-lupus membranous glomerulopathy. Author(s): Danilewicz M, Wagrowska-Danilewicz M. Source: Pol J Pathol. 2001; 52(4): 211-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11915183&dopt=Abstract
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Quantitative and qualitative analysis of the balance between type 1 and type 2 cytokine-producing CD8(-) and CD8(+) T cells in systemic lupus erythematosus. Author(s): Amel-Kashipaz MR, Huggins ML, Lanyon P, Robins A, Todd I, Powell RJ. Source: Journal of Autoimmunity. 2001 September; 17(2): 155-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591124&dopt=Abstract
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Quiz page. Mesangial lupus nephritis, WHO IIb, and severe acute tubular necrosis, secondary to gentamycin toxicity. Author(s): Fogo AB. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 November; 40(5): Xlix. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12408173&dopt=Abstract
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Rabbit anti-HMG-17 antibodies recognize similar epitopes on the HMG-17 molecule as lupus autoantibodies. Relation with histone H1 defined epitopes. Author(s): Boumba VA, Seferiadis K. Source: Journal of Peptide Science : an Official Publication of the European Peptide Society. 2002 December; 8(12): 683-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523645&dopt=Abstract
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Rapid clinical progression to diagnosis among African-American men with systemic lupus erythematosus. Author(s): Arbuckle MR, James JA, Dennis GJ, Rubertone MV, McClain MT, Kim XR, Harley JB. Source: Lupus. 2003; 12(2): 99-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630753&dopt=Abstract
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Rapidly progressive lupus glomerulonephritis and concomitant microangiopathy in an adolescent. Author(s): Blake JS, Butani L. Source: Lupus. 2002; 11(8): 533-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220108&dopt=Abstract
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Reactivation of systemic lupus erythematosus in a dialysis patient after tuberculous peritonitis. Author(s): Lui SL, Lam MF, Tse KC, Lo WK. Source: Lupus. 2002; 11(1): 49-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898920&dopt=Abstract
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Reactivities to the Sm autoantigenic complex and the synthetic SmD1-aa83-119 peptide in systemic lupus erythematosus and other autoimmune diseases. Author(s): Jaekel HP, Klopsch T, Benkenstein B, Grobe N, Baldauf A, Schoessler W, Werle E. Source: Journal of Autoimmunity. 2001 December; 17(4): 347-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771960&dopt=Abstract
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Recent advances in the genetics of systemic lupus erythematosus. Author(s): Gaffney PM, Moser KL, Graham RR, Behrens TW. Source: Rheumatic Diseases Clinics of North America. 2002 February; 28(1): 111-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840693&dopt=Abstract
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Receptor revision and systemic lupus. Author(s): Monestier M, Zouali M. Source: Scandinavian Journal of Immunology. 2002 May; 55(5): 425-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975753&dopt=Abstract
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Recognition of DNA-arginine photoadduct by anti-DNA autoantibodies in systemic lupus erythematosus. Author(s): Ahsan H, Abdi S, Ali A. Source: The Indian Journal of Medical Research. 2002 May; 115: 201-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362560&dopt=Abstract
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Reconstitution of deficient T cell receptor zeta chain restores T cell signaling and augments T cell receptor/CD3-induced interleukin-2 production in patients with systemic lupus erythematosus. Author(s): Nambiar MP, Fisher CU, Warke VG, Krishnan S, Mitchell JP, Delaney N, Tsokos GC. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1948-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847689&dopt=Abstract
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Recurrent bowel infarction in a patient with systemic lupus erythematosus. Author(s): White S, Merrie A. Source: N Z Med J. 2003 June 20; 116(1176): U483. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835811&dopt=Abstract
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Recurrent cerebral lupus heralded by an unusual combination of ocular manifestations. Author(s): Kwok AK, Wong SM, Lam SW, Lam DS. Source: Eye (London, England). 2001 August; 15(Pt 4): 559-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11767045&dopt=Abstract
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Recurrent lupus nephritis in renal transplant recipients revisited: it is not rare. Author(s): Goral S, Ynares C, Shappell SB, Snyder S, Feurer ID, Kazancioglu R, Fogo AB, Helderman JH. Source: Transplantation. 2003 March 15; 75(5): 651-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640304&dopt=Abstract
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Recurrent lupus nephritis in the second allograft of a patient with systemic lupus erythematosus. Author(s): Isaac J, Shihab FS. Source: Nephron. 2002 December; 92(4): 947-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399648&dopt=Abstract
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Recurrent lupus vulgaris following repeated BCG (Bacillus Calmette Guerin) vaccination. Author(s): Sasmaz R, Altinyazar HC, Tatlican S, Eskioglu F, Yurtsever P. Source: The Journal of Dermatology. 2001 December; 28(12): 762-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11804076&dopt=Abstract
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Recurrent pseudotumor cerebri in systemic lupus erythematosus: a case report. Author(s): Yoo WH, Park JH, Kim HK, Park TS, Baek HS. Source: Journal of Korean Medical Science. 2001 December; 16(6): 805-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748368&dopt=Abstract
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Recurrent stent thrombosis associated with lupus anticoagulant due to renal cell carcinoma. Author(s): Muir DF, Stevens A, Napier-Hemy RO, Fath-Ordoubadi F, Curzen N. Source: International Journal of Cardiovascular Interventions. 2003; 5(1): 44-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623565&dopt=Abstract
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Reduced expression of CD44 on monocytes and neutrophils in systemic lupus erythematosus: relations with apoptotic neutrophils and disease activity. Author(s): Cairns AP, Crockard AD, McConnell JR, Courtney PA, Bell AL. Source: Annals of the Rheumatic Diseases. 2001 October; 60(10): 950-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11557652&dopt=Abstract
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Reduction of serum soluble CD26/dipeptidyl peptidase IV enzyme activity and its correlation with disease activity in systemic lupus erythematosus. Author(s): Kobayashi H, Hosono O, Mimori T, Kawasaki H, Dang NH, Tanaka H, Morimoto C. Source: The Journal of Rheumatology. 2002 September; 29(9): 1858-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233879&dopt=Abstract
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Regression of subacute cutaneous lupus erythematosus in a patient with rheumatoid arthritis treated with a biologic tumor necrosis factor alpha-blocking agent: comment on the article by Pisetsky and the letter from Aringer et al. Author(s): Fautrel B, Foltz V, Frances C, Bourgeois P, Rozenberg S. Source: Arthritis and Rheumatism. 2002 May; 46(5): 1408-9; Author Reply 1409. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115253&dopt=Abstract
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Regulation of CD40 ligand expression in systemic lupus erythematosus. Author(s): Crow MK, Kirou KA. Source: Current Opinion in Rheumatology. 2001 September; 13(5): 361-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11604589&dopt=Abstract
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Regulation of the vasculature: clues from lupus. Author(s): Merrill JT. Source: Current Opinion in Rheumatology. 2002 September; 14(5): 504-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192245&dopt=Abstract
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Relation of risk of systemic lupus erythematosus to west African admixture in a Caribbean population. Author(s): Molokhia M, Hoggart C, Patrick AL, Shriver M, Parra E, Ye J, Silman AJ, McKeigue PM. Source: Human Genetics. 2003 March; 112(3): 310-8. Epub 2003 January 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12545274&dopt=Abstract
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Relationship of oncogenes (sFas, Bcl-2) and cytokines (IL-10, alfa-TNF) with the activity of systemic lupus erythematosus. Author(s): Miret C, Font J, Molina R, Garcia-Carrasco M, Filella X, Ramos M, Cervera R, Ballesta A, Ingelmo M. Source: Anticancer Res. 2001 July-August; 21(4B): 3053-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11712810&dopt=Abstract
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Relationship of tumour necrosis factor alpha gene polymorphisms and neuropsychiatric lupus. Author(s): May LA, Huang Q, Morris D, Danis V, Manolios N. Source: Lupus. 2002; 11(2): 114-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958574&dopt=Abstract
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Relationships between autoantibody responses to deletion mutants of Ki antigen and clinical manifestations of lupus. Author(s): Matsudaira R, Takeuchi K, Takasaki Y, Yano T, Matsushita M, Hashimoto H. Source: The Journal of Rheumatology. 2003 June; 30(6): 1208-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784391&dopt=Abstract
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Renal crisis in asclerodermic scleroderma--lupus overlap syndrome. Author(s): Horn HC, Ottosen P, Junker P. Source: Lupus. 2001; 10(12): 886-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11787881&dopt=Abstract
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Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term followup of a cohort of 145 patients participating in randomized controlled studies. Author(s): Illei GG, Takada K, Parkin D, Austin HA, Crane M, Yarboro CH, Vaughan EM, Kuroiwa T, Danning CL, Pando J, Steinberg AD, Gourley MF, Klippel JH, Balow JE, Boumpas DT. Source: Arthritis and Rheumatism. 2002 April; 46(4): 995-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953977&dopt=Abstract
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Renal transplantation in children with lupus nephritis. Author(s): Gipson DS, Ferris ME, Dooley MA, Huang K, Hogan SL. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 February; 41(2): 455-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552510&dopt=Abstract
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Repeated renal biopsy in proliferative lupus nephritis--predictive role of serum C1q and albuminuria. Author(s): Gunnarsson I, Sundelin B, Heimburger M, Forslid J, van Vollenhoven R, Lundberg I, Jacobson SH. Source: The Journal of Rheumatology. 2002 April; 29(4): 693-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950009&dopt=Abstract
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Reporting consistency in systemic lupus erythematosus patients: how reliable are patient histories? Author(s): Yazici Y, Erkan D, Harrison MJ, Peterson MG, Yazici H. Source: Lupus. 2002; 11(1): 46-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898919&dopt=Abstract
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Resonance assignment and secondary structure determination of a C-terminal fragment of the lupus autoantigen (La) protein containing a putative RNA recognition motif (RRM). Author(s): Jacks A, Kelly G, Curry S, Conte MR. Source: Journal of Biomolecular Nmr. 2002 April; 22(4): 387-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018493&dopt=Abstract
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Response of peripheral blood mononuclear cells from lupus patients to stimulation by CpG oligodeoxynucleotides. Author(s): Zeuner RA, Klinman DM, Illei G, Yarboro C, Ishii KJ, Gursel M, Verthelyi D. Source: Rheumatology (Oxford, England). 2003 April; 42(4): 563-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649404&dopt=Abstract
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Responsiveness of systemic lupus erythematosus T cells to signals provided through LCA T200 (CD45) and T1 (CD5) antigens. Author(s): Martorell J, Font J, Rojo I, Vilella R, Ingelmo M, Vives J. Source: Clinical and Experimental Immunology. 1989 November; 78(2): 172-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412744&dopt=Abstract
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Reticulocyte analysis in systemic lupus erythematosus and chronic renal failure using flow cytometry. Author(s): Butthep P, Jindadamrongwech S, Kaewkethong P, Panyayutho B, Wisedpanichkij R, Bunyaratvej A. Source: Asian Pac J Allergy Immunol. 2000 March; 18(1): 23-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546054&dopt=Abstract
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Retrospective analysis of outcome in a cohort of patients with lupus nephritis treated between 1977 and 1999. Author(s): MacGowan JR, Ellis S, Griffiths M, Isenberg DA. Source: Rheumatology (Oxford, England). 2002 September; 41(9): 981-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209030&dopt=Abstract
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Retroviral activity in Behcet's syndrome and systemic lupus erythematosus detected by a PCR-based reverse transcriptase assay. Author(s): McIntosh RS, Huggins ML, Kontogiannis V, Tighe PJ, Powell RJ. Source: Rheumatology International. 2001 October; 21(2): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732858&dopt=Abstract
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Reversal of CSF positivity for JC virus genome by cidofovir in a patient with systemic lupus erythematosus and progressive multifocal leukoencephalopathy. Author(s): Salmaggi A, Maccagnano E, Castagna A, Zeni S, Fantini F, Cinque P, Savoiardo M. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2001 February; 22(1): 17-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11487186&dopt=Abstract
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Reversible parkinsonism in systemic lupus erythematosus. Author(s): Tan EK, Chan LL, Auchus AP. Source: Journal of the Neurological Sciences. 2001 December 15; 193(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11718751&dopt=Abstract
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Rewriting the histological classification of lupus nephritis. Author(s): Schwartz MM, Lewis EJ. Source: Journal of Nephrology. 2002 November-December; 15 Suppl 6: S11-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515369&dopt=Abstract
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Right atrial thrombosis in systemic lupus erythematosus. Author(s): Vacca A, Garau P, Meloni L, Montisci R, Mameli A, Passiu G, Mathieu A. Source: Clin Exp Rheumatol. 2001 November-December; 19(6): 761. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791659&dopt=Abstract
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Ring-enhanced mass in the brain of a woman with systemic lupus erythematosus and elevated serum CA19-9 level: brain abscess or metastatic tumor?--case report. Author(s): Inamasu J, Nakamura Y, Saito R, Kuroshima Y, Mayanagi K, Ohba S, Nishikai M, Koyama K, Ichikizaki K. Source: Neurol Med Chir (Tokyo). 2003 January; 43(1): 43-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568322&dopt=Abstract
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Risk factors and clinical features for tuberculosis among patients with systemic lupus erythematosus in Hong Kong. Author(s): Tam LS, Li EK, Wong SM, Szeto CC. Source: Scandinavian Journal of Rheumatology. 2002; 31(5): 296-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455821&dopt=Abstract
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Risk factors and prognostic influence of infection in a single cohort of 87 adults with systemic lupus erythematosus. Author(s): Noel V, Lortholary O, Casassus P, Cohen P, Genereau T, Andre MH, Mouthon L, Guillevin L. Source: Annals of the Rheumatic Diseases. 2001 December; 60(12): 1141-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709457&dopt=Abstract
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Risk factors associated with mortality in systemic lupus erythematosus. A casecontrol study in a tertiary care center in Mexico City. Author(s): Hernandez-Cruz B, Tapia N, Villa-Romero AR, Reyes E, Cardiel MH. Source: Clin Exp Rheumatol. 2001 July-August; 19(4): 395-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11491494&dopt=Abstract
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Risk factors for cardiovascular disease in systemic lupus erythematosus. Author(s): Svenungsson E, Jensen-Urstad K, Heimburger M, Silveira A, Hamsten A, de Faire U, Witztum JL, Frostegard J. Source: Circulation. 2001 October 16; 104(16): 1887-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11602489&dopt=Abstract
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Risk factors for damage in childhood-onset systemic lupus erythematosus: cumulative disease activity and medication use predict disease damage. Author(s): Brunner HI, Silverman ED, To T, Bombardier C, Feldman BM. Source: Arthritis and Rheumatism. 2002 February; 46(2): 436-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840446&dopt=Abstract
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Risk factors for developing systemic lupus erythematosus: a case-control study in southern Sweden. Author(s): Bengtsson AA, Rylander L, Hagmar L, Nived O, Sturfelt G. Source: Rheumatology (Oxford, England). 2002 May; 41(5): 563-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011382&dopt=Abstract
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Risk factors for development of systemic lupus erythematosus: allergies, infections, and family history. Author(s): Cooper GS, Dooley MA, Treadwell EL, St Clair EW, Gilkeson GS. Source: Journal of Clinical Epidemiology. 2002 October; 55(10): 982-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464374&dopt=Abstract
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Risk factors for ovarian failure in patients with systemic lupus erythematosus. Author(s): Medeiros MM, Silveira VA, Menezes AP, Carvalho RC. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2001 December; 34(12): 1561-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11717709&dopt=Abstract
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Risk factors of mortality for salmonella infection in systemic lupus erythematosus. Author(s): Tsao CH, Chen CY, Ou LS, Huang JL. Source: The Journal of Rheumatology. 2002 June; 29(6): 1214-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064838&dopt=Abstract
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Risk of myelotoxicity with intravenous cyclophosphamide in patients with systemic lupus erythematosus. Author(s): Katsifis GE, Tzioufas AG, Vlachoyiannopoulos PG, Voulgarelis M, Moutsopoulos HM, Ioannidis JP. Source: Rheumatology (Oxford, England). 2002 July; 41(7): 780-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096228&dopt=Abstract
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Risk of periodontitis in systemic lupus erythematosus is associated with Fcgamma receptor polymorphisms. Author(s): Kobayashi T, Ito S, Yamamoto K, Hasegawa H, Sugita N, Kuroda T, Kaneko S, Narita I, Yasuda K, Nakano M, Gejyo F, Yoshie H. Source: J Periodontol. 2003 March; 74(3): 378-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12710759&dopt=Abstract
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Role of DNA methylation in transcription of human endogenous retrovirus in the pathogenesis of systemic lupus erythematosus. Author(s): Okada M, Ogasawara H, Kaneko H, Hishikawa T, Sekigawa I, Hashimoto H, Maruyama N, Kaneko Y, Yamamoto N. Source: The Journal of Rheumatology. 2002 August; 29(8): 1678-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12180729&dopt=Abstract
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Role of specialty care in the management of patients with systemic lupus erythematosus. Author(s): Urowitz MB, Kagal A, Rahman P, Gladman DD. Source: The Journal of Rheumatology. 2002 June; 29(6): 1207-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064836&dopt=Abstract
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Role of the Fcgamma receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis. Author(s): Karassa FB, Trikalinos TA, Ioannidis JP; FcgammaRIIa-SLE Meta-Analysis Investigators. Source: Arthritis and Rheumatism. 2002 June; 46(6): 1563-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12115187&dopt=Abstract
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Role of viruses in systemic lupus erythematosus and Sjogren syndrome. Author(s): James JA, Harley JB, Scofield RH. Source: Current Opinion in Rheumatology. 2001 September; 13(5): 370-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11604590&dopt=Abstract
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RP105-lacking B cells from lupus patients are responsible for the production of immunoglobulins and autoantibodies. Author(s): Kikuchi Y, Koarada S, Tada Y, Ushiyama O, Morito F, Suzuki N, Ohta A, Miyake K, Kimoto M, Horiuchi T, Nagasawa K. Source: Arthritis and Rheumatism. 2002 December; 46(12): 3259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483730&dopt=Abstract
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Ruptured renal microaneurysms complicated with a retroperitoneal abscess for a patient with systemic lupus erythematosus. Author(s): Tsai YG, Lai JH, Kuo SY, Chen HC, Wan HL, Chang DM. Source: Lupus. 2003; 12(4): 317-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729057&dopt=Abstract
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Semicircular lipoatrophy in a child with systemic lupus erythematosus after subcutaneous injections with methotrexate. Author(s): Haas N, Henz BM, Bunikowski R, Keitzer R. Source: Pediatric Dermatology. 2002 September-October; 19(5): 432-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383102&dopt=Abstract
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Serum levels of pregnenolone and 17-hydroxypregnenolone in patients with rheumatoid arthritis and systemic lupus erythematosus: relation to other adrenal hormones. Author(s): Vogl D, Falk W, Dorner M, Scholmerich J, Straub RH. Source: The Journal of Rheumatology. 2003 February; 30(2): 269-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563679&dopt=Abstract
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Serum lipoprotein(a) level and its clinical significance in patients with systemic lupus erythematosus. Author(s): Sari RA, Polat MF, Taysi S, Bakan E, Capoglu I. Source: Clinical Rheumatology. 2002 November; 21(6): 520-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447639&dopt=Abstract
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Serum oxidant/antioxidant status of patients with systemic lupus erythematosus. Author(s): Taysi S, Gul M, Sari RA, Akcay F, Bakan N. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2002 July; 40(7): 684-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12241014&dopt=Abstract
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Serum prolactin stress values in patients with systemic lupus erythematosus. Author(s): Dostal C, Moszkorzova L, Musilova L, Lacinova Z, Marek J, Zvarova J. Source: Annals of the Rheumatic Diseases. 2003 May; 62(5): 487-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695168&dopt=Abstract
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Serum thrombopoietin levels and anti-thrombopoietin antibodies in systemic lupus erythematosus. Author(s): Fureder W, Firbas U, Nichol JL, Pistillo J, Winkler S, Hiesberger H, Sperr WR, Smolen J, Schett G. Source: Lupus. 2002; 11(4): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043885&dopt=Abstract
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Severe bilateral necrotising retinitis caused by Toxoplasma gondii in a patient with systemic lupus erythematosus and diabetes mellitus. Author(s): Yamamoto JH, Boletti DI, Nakashima Y, Hirata CE, Olivalves E, Shinzato MM, Okay TS, Santo RM, Duarte MI, Kalil J. Source: The British Journal of Ophthalmology. 2003 May; 87(5): 651-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714420&dopt=Abstract
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Severe complication of a commonly prescribed drug: minocycline-induced lupus. Author(s): Shepherd J. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2002 May-June; 15(3): 239-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12038732&dopt=Abstract
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Severe lupus nephritis: importance of re-evaluating the histologic classification and the approach to patient care. Author(s): Lewis EJ, Schwartz MM, Korbet SM. Source: Journal of Nephrology. 2001 July-August; 14(4): 223-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11506244&dopt=Abstract
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Severe spongiform aortic stenosis in monozygotic twins with anti-phospholipid syndrome related to systemic lupus erythematosus. Author(s): Chandar S, Riminton S, Yiannikas J, Kritharides L. Source: Rheumatology (Oxford, England). 2003 April; 42(4): 599-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649410&dopt=Abstract
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Severe subacute cutaneous lupus erythematosus presenting with generalized erythroderma and bullae. Author(s): Mutasim DF. Source: Journal of the American Academy of Dermatology. 2003 June; 48(6): 947-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789191&dopt=Abstract
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Severe thrombocytopenic purpura due to rubella infection in a patient with systemic lupus erythematosus. Author(s): Boehlen F, Balavoine JF, de Moerloose P. Source: Lupus. 2003; 12(2): 144-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630761&dopt=Abstract
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Sex hormones and systemic lupus erythematosus: review and meta-analysis. Author(s): McMurray RW, May W. Source: Arthritis and Rheumatism. 2003 August; 48(8): 2100-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12905462&dopt=Abstract
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Shwartzman phenomenon in a patient with active systemic lupus erythematosus preceding fatal disseminated intravascular coagulation. Author(s): Riemekasten G, Ziemer S, Haupl T, Melzer C, Loddenkemper K, Hauptmann S, Burmester GR, Hiepe F. Source: Lupus. 2002; 11(4): 204-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043882&dopt=Abstract
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Silent nephritis in systemic lupus erythematosus. Author(s): Zabaleta-Lanz M, Vargas-Arenas RE, Tapanes F, Daboin I, Atahualpa Pinto J, Bianco NE. Source: Lupus. 2003; 12(1): 26-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587823&dopt=Abstract
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Single photon emission computed tomography of technetium-99m tetrofosmin myocardial perfusion imaging in patients with systemic lupus erythematosus--a preliminary report. Author(s): Lin JJ, Hsu HB, Sun SS, Wang JJ, Ho ST, Kao CH. Source: Japanese Heart Journal. 2003 January; 44(1): 83-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622440&dopt=Abstract
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SLE--systemic lupus erythematosus: a BLySful, yet BAFFling, disorder. Author(s): Stohl W. Source: Arthritis Research & Therapy. 2003; 5(3): 136-8. Epub 2003 March 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723979&dopt=Abstract
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Small-bowel arteriovenous shunting due to systemic lupus erythematosus vasculitis. Author(s): Inyang AN, Ulrrich H. Source: American Journal of Critical Care : an Official Publication, American Association of Critical-Care Nurses. 2003 May; 12(3): 242-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751399&dopt=Abstract
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Smoking, alcohol consumption, and risk of systemic lupus erythematosus in the Black Women's Health Study. Author(s): Formica MK, Palmer JR, Rosenberg L, McAlindon TE. Source: The Journal of Rheumatology. 2003 June; 30(6): 1222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784393&dopt=Abstract
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Some controversies of neuropsychiatric systemic lupus erythematosus. Author(s): Omdal R. Source: Scandinavian Journal of Rheumatology. 2002; 31(4): 192-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369649&dopt=Abstract
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Spastic quadriparesis: an unusual early manifestation of systemic lupus erythematosus. Author(s): Gupta A, Singh S, Singh P, Ahluwalia J, Rath S, Minz RW. Source: Scandinavian Journal of Rheumatology. 2003; 32(3): 189-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892260&dopt=Abstract
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Specific antibody response after influenza immunization in systemic lupus erythematosus. Author(s): Abu-Shakra M, Press J, Varsano N, Levy V, Mendelson E, Sukenik S, Buskila D. Source: The Journal of Rheumatology. 2002 December; 29(12): 2555-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465151&dopt=Abstract
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Spontaneous dissection of coronary artery treated by primary stenting as the first presentation of systemic lupus erythematosus. Author(s): Aldoboni AH, Hamza EA, Majdi K, Ngibzadhe M, Palasaidi S, Moayed DA. Source: J Invasive Cardiol. 2002 November; 14(11): 694-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403902&dopt=Abstract
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Spontaneous, bilateral patellar tendon rupture in a woman with previous Achilles tendon rupture and systemic lupus erythematosus. Author(s): Prasad S, Lee A, Clarnette R, Faull R. Source: Rheumatology (Oxford, England). 2003 July; 42(7): 905-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826711&dopt=Abstract
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Stratification of pedigrees multiplex for systemic lupus erythematosus and for selfreported rheumatoid arthritis detects a systemic lupus erythematosus susceptibility gene (SLER1) at 5p15.3. Author(s): Namjou B, Nath SK, Kilpatrick J, Kelly JA, Reid J, James JA, Harley JB. Source: Arthritis and Rheumatism. 2002 November; 46(11): 2937-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428235&dopt=Abstract
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Structural, quantitative and functional comparison of amyloid P component in sera from patients with systemic lupus erythematosus and healthy donors. Author(s): Sen JW, Recke C, Rahbek L, Skogstrand K, Heegaard NH. Source: Scandinavian Journal of Immunology. 2002 December; 56(6): 645-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12472678&dopt=Abstract
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Studies of human polyclonal and monoclonal antibodies binding to lupus autoantigens and cross-reactive antigens. Author(s): Sharma A, Isenberg D, Diamond B. Source: Rheumatology (Oxford, England). 2003 March; 42(3): 453-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626796&dopt=Abstract
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Subacute abdominal pain requiring hospitalization in a systemic lupus erythematosus patient: a retrospective analysis and review of the literature. Author(s): Buck AC, Serebro LH, Quinet RJ. Source: Lupus. 2001; 10(7): 491-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480847&dopt=Abstract
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Subacute cutaneous lupus erythematosus associated with phenytoin. Author(s): Ross S, Ormerod AD, Roberts C, Dwyer C, Herriot R. Source: Clinical and Experimental Dermatology. 2002 September; 27(6): 474-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372089&dopt=Abstract
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Subacute cutaneous lupus erythematosus in a patient with rheumatoid arthritis. Author(s): Pantoja L, Gonzalez-Lopez MA, Bouso M, Alija A, Ortiz-Saracho J. Source: Scandinavian Journal of Rheumatology. 2002; 31(6): 377-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12492256&dopt=Abstract
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Subacute cutaneous lupus erythematosus in childhood. Author(s): Amato L, Coronella G, Berti S, Moretti S, Fabbri P. Source: Pediatric Dermatology. 2003 January-February; 20(1): 31-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558843&dopt=Abstract
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Subacute lupus erythematosus-like eruption due to terbinafine: report of three cases. Author(s): Hill VA, Chow J, Cowley N, Marsden RA. Source: The British Journal of Dermatology. 2003 May; 148(5): 1056. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786843&dopt=Abstract
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Subcutaneous, intramuscular, and intraosseous synovial cyst formation around the knee in rheumatoid arthritis/systemic lupus erythematosus overlap syndrome. Author(s): Yamamoto T, Akisue O, Marui T, Kawamoto T, Nagira K, Nakagawa A, Yoshiya S, Kurosaka M. Source: The Journal of Rheumatology. 2003 June; 30(6): 1351-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784415&dopt=Abstract
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Subdural empyema with extension to vertebral canal secondary to salmonellosis in a patient with systemic lupus erythematosus. Author(s): Alvarez Sastre C, Villarejo F, Lopez Robledillo JC, Martin-Gamero AP, Perez Diaz C. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2002 October; 18(9-10): 528-31. Epub 2002 August 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382181&dopt=Abstract
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Successful management of life-threatening hemorrhage in a patient with synchronous lupus anticoagulant and factor VIII inhibitor. Author(s): Brings HA, Waas JK, McCrae KR, Baele HR, Goldstone J. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2002 October; 36(4): 853-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368750&dopt=Abstract
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Successful treatment of chronic discoid lupus erythematosus of the scalp with imiquimod. Author(s): Gerdsen R, Wenzel J, Uerlich M, Bieber T, Petrow W. Source: Dermatology (Basel, Switzerland). 2002; 205(4): 416-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444344&dopt=Abstract
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Successful treatment of leucocytoclastic vasculitis and pancytopenia secondary to systemic lupus erythematosus with intravenous immunoglobulin. Author(s): Perez C, Guarch R, Rodrigo M, Gallego M, Ormazabal O. Source: The British Journal of Dermatology. 2002 July; 147(1): 180-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100207&dopt=Abstract
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Successful treatment of patients with systemic lupus erythematosus by immunoadsorption with a C1q column: a pilot study. Author(s): Pfueller B, Wolbart K, Bruns A, Burmester GR, Hiepe F. Source: Arthritis and Rheumatism. 2001 August; 44(8): 1962-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11508450&dopt=Abstract
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Successful treatment of subacute cutaneous lupus erythematosus with mycophenolate mofetil. Author(s): Schanz S, Ulmer A, Rassner G, Fierlbeck G. Source: The British Journal of Dermatology. 2002 July; 147(1): 174-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12100205&dopt=Abstract
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Suicide attempts in patients with systemic lupus erythematosus. Author(s): Karassa FB, Magliano M, Isenberg DA. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 58-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480670&dopt=Abstract
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Sulphasalazine-induced systemic lupus erythematous in a patient with ankylosing spondylitis. Author(s): Tsai WC, Chen CJ, Yen JH, Liu HW. Source: Clinical Rheumatology. 2002 August; 21(4): 339-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296286&dopt=Abstract
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Synchronised therapy and high-dose cyclophosphamide in proliferative lupus nephritis. Author(s): Danieli MG, Palmieri C, Salvi A, Refe MC, Strusi AS, Danieli G. Source: Journal of Clinical Apheresis. 2002; 17(2): 72-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210709&dopt=Abstract
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Systemic and discoid lupus erythematosus in HIV-infected patients treated with highly active antiretroviral therapy. Author(s): Calza L, Manfredi R, Colangeli V, D'Antuono A, Passarini B, Chiodo F. Source: International Journal of Std & Aids. 2003 May; 14(5): 356-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803945&dopt=Abstract
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Systemic lupus erythematosus among Arabs. Author(s): Habib GS, Saliba WR. Source: Isr Med Assoc J. 2002 September; 4(9): 690-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440232&dopt=Abstract
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Systemic lupus erythematosus and microchimerism in autoimmunity. Author(s): Abbud Filho M, Pavarino-Bertelli EC, Alvarenga MP, Fernandes IM, Toledo RA, Tajara EH, Savoldi-Barbosa M, Goldmann GH, Goloni-Bertollo EM. Source: Transplantation Proceedings. 2002 November; 34(7): 2951-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12431669&dopt=Abstract
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Systemic lupus erythematosus and related autoimmune diseases are antigen-driven, epigenetic diseases. Author(s): Brooks WH. Source: Medical Hypotheses. 2002 December; 59(6): 736-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445518&dopt=Abstract
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Systemic lupus erythematosus and rheumatoid arthritis patients differ from healthy controls in their cytokine pattern after stress exposure. Author(s): Jacobs R, Pawlak CR, Mikeska E, Meyer-Olson D, Martin M, Heijnen CJ, Schedlowski M, Schmidt RE. Source: Rheumatology (Oxford, England). 2001 August; 40(8): 868-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11511755&dopt=Abstract
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Systemic lupus erythematosus in childhood. Author(s): Klein-Gitelman M, Reiff A, Silverman ED. Source: Rheumatic Diseases Clinics of North America. 2002 August; 28(3): 561-77, Vi-Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380370&dopt=Abstract
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Systemic lupus erythematosus in children with sickle cell disease. Author(s): Saxena VR, Mina R, Moallem HJ, Rao SP, Miller ST. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 August; 25(8): 668-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12902927&dopt=Abstract
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Systemic lupus erythematosus in children: a case report and review. Author(s): Kemiki AD, Jimmy S, Rongap A. Source: P N G Med J. 2001 March-June; 44(1-2): 57-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418679&dopt=Abstract
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Systemic lupus erythematosus in the far north of Queensland. Author(s): Bossingham D. Source: Lupus. 2003; 12(4): 327-31. Erratum In: Lupus. 2003; 12(6): 494. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729060&dopt=Abstract
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Systemic lupus erythematosus in the intensive care unit. Author(s): Raj R, Murin S, Matthay RA, Wiedemann HP. Source: Critical Care Clinics. 2002 October; 18(4): 781-803. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418441&dopt=Abstract
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Systemic lupus erythematosus in three ethnic groups: XV. Prevalence and correlates of fibromyalgia. Author(s): Friedman AW, Tewi MB, Ahn C, McGwin G Jr, Fessler BJ, Bastian HM, Baethge BA, Reveille JD, Alarcon GS; LUMINA Study Group. Source: Lupus. 2003; 12(4): 274-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729050&dopt=Abstract
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Systemic lupus erythematosus initially presenting as idiopathic juvenile arthritis with positive antinuclear antibodies. Author(s): Vuilleumier C, Sauvain MJ, Aebi C, Saurenmann T, Bianchetti MG. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 April; 92(4): 512-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801125&dopt=Abstract
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Systemic lupus erythematosus with anti-Hu antibodies and polyradiculoneuropathy. Author(s): Carpentier AF, Chassande B, Amoura Z, Benyahia B, Piette JC, Delattre JY. Source: Neurology. 2001 August 14; 57(3): 558-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502940&dopt=Abstract
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Systemic lupus erythematosus. Author(s): Wallace DJ. Source: Drugs Today (Barc). 2002 April; 38(4): 259-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12532194&dopt=Abstract
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Systemic lupus erythematosus. Early identification, co-management are key NP contributions. Author(s): Mulvihill K. Source: Adv Nurse Pract. 2003 January; 11(1): 32-6; Quiz 36-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630256&dopt=Abstract
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Systemic lupus erythematosus-associated anetoderma and anti-phospholipid antibodies. Author(s): Fernandez-Galar M, Espana A, Lloret P. Source: Clinical and Experimental Dermatology. 2003 January; 28(1): 39-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558628&dopt=Abstract
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Systemic lupus erythematosus-associated pulmonary hypertension: good outcome following sildenafil therapy. Author(s): Molina J, Lucero E, Luluaga S, Bellomio V, Spindler A, Berman A. Source: Lupus. 2003; 12(4): 321-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729058&dopt=Abstract
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T(H)1/T(H)2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients. Author(s): Munoz-Valle JF, Vazquez-Del Mercado M, Garcia-Iglesias T, Orozco-Barocio G, Bernard-Medina G, Martinez-Bonilla G, Bastidas-Ramirez BE, Navarro AD, Bueno M, Martinez-Lopez E, Best-Aguilera CR, Kamachi M, Armendariz-Borunda J. Source: Clinical and Experimental Immunology. 2003 February; 131(2): 377-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562402&dopt=Abstract
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TAP1 and TAP2 polymorphisms analysis in northwestern Colombian patients with systemic lupus erythematosus. Author(s): Correa PA, Molina JF, Pinto LF, Arcos-Burgos M, Herrera M, Anaya JM. Source: Annals of the Rheumatic Diseases. 2003 April; 62(4): 363-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634240&dopt=Abstract
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Testing for lupus. Author(s): Colyar MR. Source: Adv Nurse Pract. 2002 March; 10(3): 31. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418334&dopt=Abstract
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TG or not TG: IgG-anti-tissue transglutaminase in systemic lupus erythematosus: new role for an old enzyme. Author(s): Tanay A, Brickman CM, Gas S, Misgav N, Frayman A, Lehman D. Source: Isr Med Assoc J. 2002 November; 4(11 Suppl): 878-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455168&dopt=Abstract
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Thalidomide for treatment of severe generalized discoid lupus lesions in two patients with systemic lupus erythematosus. Author(s): Alfadley A, Al-Rayes H, Hussein W, Al-Dalaan A, Al-Aboud K. Source: Journal of the American Academy of Dermatology. 2003 May; 48(5 Suppl): S8991. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734488&dopt=Abstract
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The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells. Author(s): Kaplan MJ, Lewis EE, Shelden EA, Somers E, Pavlic R, McCune WJ, Richardson BC. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 November 15; 169(10): 6020-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421989&dopt=Abstract
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The association of myasthenia gravis and connective tissue diseases. Effects of thymectomy in six cases with rheumatoid arthritis and one case with systemic lupus erythematosus. Author(s): Tellez-Zenteno JF, Remes-Troche JM, Mimenza-Alvarado A, Garcia-Ramos G, Estanol B, Vega-Boada F. Source: Neurologia (Barcelona, Spain). 2003 March; 18(2): 54-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12610753&dopt=Abstract
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The autoimmune response to chromatin antigens in systemic lupus erythematosus: autoantibodies against histone H1 are a highly specific marker for SLE associated with increased disease activity. Author(s): Schett G, Smole J, Zimmermann C, Hiesberger H, Hoefler E, Fournel S, Muller S, Rubin RL, Steiner G. Source: Lupus. 2002; 11(11): 704-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12475000&dopt=Abstract
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The cardiovascular burden of lupus: a complex challenge. Author(s): Schattner A, Liang MH. Source: Archives of Internal Medicine. 2003 July 14; 163(13): 1507-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860571&dopt=Abstract
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The coexistence of cutaneous vasculitis and thrombosis in childhood-onset systemic lupus erythematosus with antiphospholipid antibodies. Author(s): Tomizawa K, Sato-Matsumura KC, Kajii N. Source: The British Journal of Dermatology. 2003 August; 149(2): 439-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12932270&dopt=Abstract
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The concomitant presence of lupus anticoagulant, anticardiolipin and anti-beta2glycoprotein i antibodies could be associated with acquired activated protein c resistance in non-systemic lupus erythematosus patients. Author(s): Gennari L, Blanco A, Alberto MF, Grosso S, Lazzari MA. Source: British Journal of Haematology. 2003 May; 121(3): 527-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716380&dopt=Abstract
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The effect of lupus anticoagulant in the second-generation assay for activated protein C resistance. Author(s): Ragland BD, Reed CE, Eiland BM, Tichenor PH, Hudson CL, Fritsma GA, Adler BK, Marques MB. Source: American Journal of Clinical Pathology. 2003 January; 119(1): 66-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520699&dopt=Abstract
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The evidence base for the treatment of lupus nephritis in the new millennium. Author(s): Adu D. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 August; 16(8): 1536-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11477149&dopt=Abstract
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The frequency of thrombotic thrombocytopenic purpura in patients with systemic lupus erythematosus undergoing kidney biopsy. Author(s): Manadan AM, Harris C, Schwartz MM, Block JA. Source: The Journal of Rheumatology. 2003 June; 30(6): 1227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784394&dopt=Abstract
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The global impact of systemic lupus erythematosus. Author(s): Richards JS. Source: Ethn Dis. 2003 Spring; 13(2): 175-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785412&dopt=Abstract
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The impact of the 1997 update of the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus: what has been changed? Author(s): Feletar M, Ibanez D, Urowitz MB, Gladman DD. Source: Arthritis and Rheumatism. 2003 July; 48(7): 2067-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847702&dopt=Abstract
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The inducible nitric oxide synthase promoter polymorphism does not confer susceptibility to systemic lupus erythematosus. Author(s): Lopez-Nevot MA, Ramal L, Jimenez-Alonso J, Martin J. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509623&dopt=Abstract
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The potential of human regulatory T cells generated ex vivo as a treatment for lupus and other chronic inflammatory diseases. Author(s): Horwitz DA, Gray JD, Zheng SG. Source: Arthritis Research. 2002; 4(4): 241-6. Epub 2002 March 12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12106494&dopt=Abstract
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The prevalence of neuropsychiatric syndromes in systemic lupus erythematosus. Author(s): Ainiala H, Loukkola J, Peltola J, Korpela M, Hietaharju A. Source: Neurology. 2001 August 14; 57(3): 496-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11502919&dopt=Abstract
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The relationship of FcgammaRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus. Author(s): Anolik JH, Campbell D, Felgar RE, Young F, Sanz I, Rosenblatt J, Looney RJ. Source: Arthritis and Rheumatism. 2003 February; 48(2): 455-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571855&dopt=Abstract
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The risk of pregnancy in patients with lupus nephritis. Author(s): Moroni G, Ponticelli C. Source: Journal of Nephrology. 2003 March-April; 16(2): 161-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768062&dopt=Abstract
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The role of VH determinants in systemic lupus erythematosus. Author(s): Kalsi JK, Hahn BH. Source: Lupus. 2002; 11(12): 878-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529054&dopt=Abstract
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The three most common CARD15 mutations associated with Crohn's disease and the chromosome 16 susceptibility locus for systemic lupus erythematosus. Author(s): Ferreiros-Vidal I, Garcia-Meijide J, Carreira P, Barros F, Carracedo A, GomezReino JJ, Gonzalez A. Source: Rheumatology (Oxford, England). 2003 April; 42(4): 570-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649405&dopt=Abstract
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The transforming growth factor-beta1 gene polymorphism (G915C) is not associated with systemic lupus erythematosus. Author(s): Schotte H, Willeke P, Rust S, Assmann G, Domschke W, Gaubitz M, Schluter B. Source: Lupus. 2003; 12(2): 86-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12630751&dopt=Abstract
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The treatment of lupus nephritis: revisiting Galen. Author(s): Lewis EJ. Source: Annals of Internal Medicine. 2001 August 21; 135(4): 296-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11511144&dopt=Abstract
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The use of laboratory tests in diagnosis and monitoring of systemic lupus erythematosus. Author(s): Sinico RA, Bollini B, Sabadini E, Di Toma L, Radice A. Source: Journal of Nephrology. 2002 November-December; 15 Suppl 6: S20-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515370&dopt=Abstract
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Thrombinography shows acquired resistance to activated protein C in patients with lupus anticoagulants. Author(s): Regnault V, Beguin S, Wahl D, de Maistre E, Coenraad Hemker H, Lecompte T. Source: Thrombosis and Haemostasis. 2003 February; 89(2): 208-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12574797&dopt=Abstract
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Thrombocytopenia identifies a severe familial phenotype of systemic lupus erythematosus and reveals genetic linkages at 1q22 and 11p13. Author(s): Scofield RH, Bruner GR, Kelly JA, Kilpatrick J, Bacino D, Nath SK, Harley JB. Source: Blood. 2003 February 1; 101(3): 992-7. Epub 2002 September 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393658&dopt=Abstract
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Thymus function in drug-induced lupus. Author(s): Rubin RL, Salomon DR, Guerrero RS. Source: Lupus. 2001; 10(11): 795-801. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789489&dopt=Abstract
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Time between onset of apoptosis and release of nucleosomes from apoptotic cells: putative implications for systemic lupus erythematosus. Author(s): van Nieuwenhuijze AE, van Lopik T, Smeenk RJ, Aarden LA. Source: Annals of the Rheumatic Diseases. 2003 January; 62(1): 10-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480662&dopt=Abstract
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Time perspective predicts the progression of permanent organ damage in patients with systemic lupus erythematosus. Author(s): Sundaramurthy S, Bush TM, Neuwelt CM, Ward MM. Source: Lupus. 2003; 12(6): 443-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873045&dopt=Abstract
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Tinea faciei mimicking cutaneous lupus erythematosus: a histopathologic case report. Author(s): Meymandi S, Wiseman MC, Crawford RI. Source: Journal of the American Academy of Dermatology. 2003 February; 48(2 Suppl): S7-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582372&dopt=Abstract
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Topical tacrolimus for cutaneous lupus erythematosus. Author(s): Chambers CA. Source: The British Journal of Dermatology. 2003 April; 148(4): 829; Author Reply 829. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752154&dopt=Abstract
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Transient panhypogammaglobulinaemia and B-lymphocyte deficiency in a patient with neuropsychiatric systemic lupus erythematosus after immunosuppressive therapy. Author(s): Song J, Park YB, Suh CH, Lee SK. Source: Clinical Rheumatology. 2003 February; 22(1): 62-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605322&dopt=Abstract
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Treatment of cutaneous lupus with Elidel. Author(s): Zabawski E. Source: Dermatology Online Journal [electronic Resource]. 2002 October; 8(2): 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546779&dopt=Abstract
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Treatment of diffuse proliferative lupus glomerulonephritis: a comparison of two cyclophosphamide-containing regimens. Author(s): Mok CC, Ho CT, Siu YP, Chan KW, Kwan TH, Lau CS, Wong RW, Au TC. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 August; 38(2): 256-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11479150&dopt=Abstract
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Treatment of lupus erythematosus with pulsed dye laser. Author(s): Baniandres O, Boixeda P, Belmar P, Perez A. Source: Lasers in Surgery and Medicine. 2003; 32(4): 327-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696102&dopt=Abstract
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Treatment of lupus nephritis. Author(s): Hejaili FF, Moist LM, Clark WF. Source: Drugs. 2003; 63(3): 257-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12534331&dopt=Abstract
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Treatment of lupus psychosis with oral cyclophosphamide followed by azathioprine maintenance: an open-label study. Author(s): Mok CC, Lau CS, Wong RW. Source: The American Journal of Medicine. 2003 July; 115(1): 59-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867236&dopt=Abstract
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Treatment of membranous lupus nephritis with prednisone, azathioprine and cyclosporin A. Author(s): Tam LS, Li EK, Szeto CC, Wong SM, Leung CB, Lai FM, Wong KC, Lui SF. Source: Lupus. 2001; 10(11): 827-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789496&dopt=Abstract
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Treatment of pulmonary hemorrhage in childhood systemic lupus erythematosus with mycophenolate mofetil. Author(s): Samad AS, Lindsley CB. Source: Southern Medical Journal. 2003 July; 96(7): 705-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940327&dopt=Abstract
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Treatment of severe proliferative lupus nephritis: the current state. Author(s): Mok CC, Wong RW, Lai KN. Source: Annals of the Rheumatic Diseases. 2003 September; 62(9): 799-804. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12922948&dopt=Abstract
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Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial. Author(s): Kalunian KC, Davis JC Jr, Merrill JT, Totoritis MC, Wofsy D; IDEC-131 Lupus Study Group. Source: Arthritis and Rheumatism. 2002 December; 46(12): 3251-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483729&dopt=Abstract
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Treatment of systemic lupus erythematosus-associated type B insulin resistance syndrome with cyclophosphamide and mycophenolate mofetil. Author(s): Gehi A, Webb A, Nolte M, Davis J Jr. Source: Arthritis and Rheumatism. 2003 April; 48(4): 1067-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12687550&dopt=Abstract
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Treatment side effects. Case 3. Fluorouracil-induced exacerbation of systemic lupus erythematosus. Author(s): Moazzam N, Malik AA, Mehdi SA, Potti A. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2002 July 1; 20(13): 3032-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089235&dopt=Abstract
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Treatment with gonadotropin-releasing hormone agonists and prevention of multiple gestations in lupus or antiphospholipid syndrome patients undergoing in vitro fertilization: comment on the article by Guballa et al. Author(s): Blumenfeld Z. Source: Arthritis and Rheumatism. 2002 September; 46(9): 2542; Author Reply 2542. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355508&dopt=Abstract
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Tumid lupus erythematosus: criteria for classification with immunohistochemical analysis. Author(s): Alexiades-Armenakas MR, Baldassano M, Bince B, Werth V, Bystryn JC, Kamino H, Soter NA, Franks AG Jr. Source: Arthritis and Rheumatism. 2003 August 15; 49(4): 494-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12910555&dopt=Abstract
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Tumour necrosis factor alpha in systemic lupus erythematosus and anti-DNA autoantibody production. Author(s): Mageed RA, Isenberg DA. Source: Lupus. 2002; 11(12): 850-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529050&dopt=Abstract
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Type V hyperlipoproteinemia in systemic lupus erythematosus. Author(s): Nakane T, Asayama K, Higashida K, Hayashibe H, Uchida N, Dobashi K, Kodera K, Tandou T, Furuich Y, Nakazawa S. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 June; 45(3): 352-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828597&dopt=Abstract
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Type-I interferon receptor deficiency reduces lupus-like disease in NZB mice. Author(s): Santiago-Raber ML, Baccala R, Haraldsson KM, Choubey D, Stewart TA, Kono DH, Theofilopoulos AN. Source: The Journal of Experimental Medicine. 2003 March 17; 197(6): 777-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642605&dopt=Abstract
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Ulcerating plantar keratoderma in association with systemic lupus erythematosus. Author(s): Grossberg EB, Scherschun L, Fivenson DP. Source: Lupus. 2001; 10(9): 650-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11678455&dopt=Abstract
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Ultrastructural and biosynthetic characteristics of glomerular endotheliocytes and periglomerular arterioles during systemic lupus erythematosus. Author(s): Chapaeva NN, Nepomnyashchikh GI, Aidagulova SV, Bakarev MA. Source: Bulletin of Experimental Biology and Medicine. 2001 August; 132(2): 791-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11713569&dopt=Abstract
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Ultraviolet light exposure is not a requirement for the development of cutaneous neonatal lupus. Author(s): Cimaz R, Biggioggero M, Catelli L, Muratori S, Cambiaghi S. Source: Lupus. 2002; 11(4): 257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12043891&dopt=Abstract
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Uncommon causes of liver disease in juvenile systemic lupus erythematosus. Author(s): Ravelli A, Caria MC, Malattia C, Temporini F, Cavallero A, Silini EM, Martini A. Source: Clin Exp Rheumatol. 2001 July-August; 19(4): 474. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11491509&dopt=Abstract
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Uncommon syndromes and treatment manifestations of malignancy: Case 1. Unusual association of lupus and sarcoma. Author(s): Rossi G, Lucioni M, Sammarchi L, Paulli M, Beluffi G, Martini A, Ravelli A. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 January 1; 21(1): 166-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12506186&dopt=Abstract
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Understanding patient preferences for the treatment of lupus nephritis with adaptive conjoint analysis. Author(s): Fraenkel L, Bodardus S, Wittnik DR, Wittink DR. Source: Medical Care. 2001 November; 39(11): 1203-16. Erratum In: Med Care. 2003 May; 41(5): 574. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11606874&dopt=Abstract
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Undiagnosed systemic lupus erythematosus presenting with salmonella bacteremia: a case report and mini-review. Author(s): Gencer S, Balkan YY, Benzonana N, Ozer S. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 June; 9(6): 572-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848738&dopt=Abstract
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Unilateral tumid lupus erythematosus. Author(s): Pacheco TR, Spates ST, Lee LA. Source: Lupus. 2002; 11(6): 388-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12139378&dopt=Abstract
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Unusual coronary artery aneurysm and acute myocardial infarction in a middle-aged man with systemic lupus erythematosus. Author(s): Uchida T, Inoue T, Kamishirado H, Nakata T, Sakai Y, Takayanagi K, Morooka S. Source: The American Journal of the Medical Sciences. 2001 September; 322(3): 163-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11570783&dopt=Abstract
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Update on complement in the pathogenesis of systemic lupus erythematosus. Author(s): Molina H. Source: Current Opinion in Rheumatology. 2002 September; 14(5): 492-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192243&dopt=Abstract
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Update on the treatment of systemic lupus erythematosus: therapeutic highlights from the Sixth International Lupus Conference. Author(s): Abu-Shakra M, Buskila D. Source: Isr Med Assoc J. 2002 January; 4(1): 71-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11802320&dopt=Abstract
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Upregulation of epidermal surface molecule expression in primary and ultravioletinduced lesions of lupus erythematosus tumidus. Author(s): Kuhn A, Sonntag M, Sunderkotter C, Lehmann P, Vestweber D, Ruzicka T. Source: The British Journal of Dermatology. 2002 May; 146(5): 801-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12000376&dopt=Abstract
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Urinary soluble VCAM-1 in systemic lupus erythematosus: a clinical marker for monitoring disease activity and damage. Author(s): Molad Y, Miroshnik E, Sulkes J, Pitlik S, Weinberger A, Monselise Y. Source: Clin Exp Rheumatol. 2002 May-June; 20(3): 403-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102480&dopt=Abstract
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Use of 0.1% tacrolimus ointment in patients with various forms of lupus erythematosus. Author(s): Walker SL, Kirby B, Chalmers RJ. Source: Eur J Dermatol. 2002 July-August; 12(4): 387-8; Author Reply 389. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095891&dopt=Abstract
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Use of genetic knockouts to modulate disease expression in a murine model of lupus, MRL/lpr mice. Author(s): Reilly CM, Gilkeson GS. Source: Immunologic Research. 2002; 25(2): 143-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999168&dopt=Abstract
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Use of patient age and anti-Ro/La antibody status to determine the probability of patients with systemic lupus erythematosus and sicca symptoms fulfilling criteria for secondary Sjogren's syndrome. Author(s): Prabu A, Marshall T, Gordon C, Plant T, Bawendi A, Heaton S, Jobson S, Briggs D, Bowman SJ. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 189-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509639&dopt=Abstract
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Use of single photon emission computed tomography and magnetic resonance to evaluate central nervous system involvement in patients with juvenile systemic lupus erythematosus. Author(s): Prismich G, Hilario MO, Len CA, Terreri MT, Quaresma MR, Alonso G, Sevillano MM, Lederman HM. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2002 July; 35(7): 805-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12131920&dopt=Abstract
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Validation of a Systemic Lupus Activity Questionnaire (SLAQ) for population studies. Author(s): Karlson EW, Daltroy LH, Rivest C, Ramsey-Goldman R, Wright EA, Partridge AJ, Liang MH, Fortin PR. Source: Lupus. 2003; 12(4): 280-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12729051&dopt=Abstract
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Validity of the new American College of Rheumatology criteria for neuropsychiatric lupus syndromes: a population-based evaluation. Author(s): Ainiala H, Hietaharju A, Loukkola J, Peltola J, Korpela M, Metsanoja R, Auvinen A. Source: Arthritis and Rheumatism. 2001 October; 45(5): 419-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11642640&dopt=Abstract
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Vascular endothelial growth factor plasma levels in patients with systemic lupus erythematosus and primary antiphospholipid syndrome. Author(s): Navarro C, Candia-Zuniga L, Silveira LH, Ruiz V, Gaxiola M, Avila MC, Amigo MC. Source: Lupus. 2002; 11(1): 21-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898914&dopt=Abstract
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Venous stasis ulcers due to primary, isolated deep venous insufficiency in a patient with systemic lupus erythematosus: report of a case. Author(s): Nishibe T, Kudo F, Flores J, Imai T, Miyazaki K, Yasuda K. Source: Surgery Today. 2002; 32(10): 934-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12376799&dopt=Abstract
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Verrucous form of chilblain lupus erythematosus. Author(s): Pock L, Petrovska P, Becvar R, Mandys V, Hercogova J. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2001 September; 15(5): 448-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11763388&dopt=Abstract
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Vesiculobullous systemic lupus erythematosus: a case with circulating IgG and IgA autoantibodies to type VII collagen. Author(s): Nitta Y, Kawamura C, Hashimoto T. Source: Journal of the American Academy of Dermatology. 2002 November; 47(5 Suppl): S283-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399753&dopt=Abstract
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VH4-34 encoded antibody in systemic lupus erythematosus: effect of isotype. Author(s): Bhat NM, Lee LM, van Vollenhoven RF, Teng NN, Bieber MM. Source: The Journal of Rheumatology. 2002 October; 29(10): 2114-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375320&dopt=Abstract
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Visceral leishmaniasis as a cause of unexplained fever and cytopenia in systemic lupus erythematosus. Author(s): Ravelli A, Viola S, De Benedetti F, Magni Manzoni S, Martini A. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(2): 246-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11952019&dopt=Abstract
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Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus. Author(s): Graham RR, Ortmann WA, Langefeld CD, Jawaheer D, Selby SA, Rodine PR, Baechler EC, Rohlf KE, Shark KB, Espe KJ, Green LE, Nair RP, Stuart PE, Elder JT, King RA, Moser KL, Gaffney PM, Bugawan TL, Erlich HA, Rich SS, Gregersen PK, Behrens TW. Source: American Journal of Human Genetics. 2002 September; 71(3): 543-53. Epub 2002 July 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145745&dopt=Abstract
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Vitamin K deficiency in diffuse alveolar hemorrhage associated with systemic lupus erythematosus. Author(s): Christopher K, Hong M, Yodice PC. Source: Respiration; International Review of Thoracic Diseases. 2001; 68(6): 658. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786727&dopt=Abstract
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Warning: thalidomide-related thrombotic risk potentially concerns patients with lupus. Author(s): Piette JC, Sbai A, Frances C. Source: Lupus. 2002; 11(2): 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958580&dopt=Abstract
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What do we know about lupus membranous nephropathy? An analytic review. Author(s): Kolasinski SL, Chung JB, Albert DA. Source: Arthritis and Rheumatism. 2002 Aug15; 47(4): 450-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12209494&dopt=Abstract
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What is your diagnosis? Lupus profundus. Author(s): Pichardo RO, Lu D, Sangueza OP, Selim MA. Source: The American Journal of Dermatopathology. 2002 December; 24(6): 507-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481774&dopt=Abstract
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Who should look after patients with mild lupus? Author(s): Glazier RH. Source: The Journal of Rheumatology. 2002 June; 29(6): 1115-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12064821&dopt=Abstract
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Why the lupus problem remains unsolved and I am a human geneticist. Author(s): German J. Source: Lupus. 2003; 12(3): 181-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12708778&dopt=Abstract
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Workshop report on some new ideas about the treatment of systemic lupus erythematosus. Author(s): Linnik M, Staines NA, Berden J, Isenberg DA. Source: Lupus. 2002; 11(12): 793-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529043&dopt=Abstract
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CHAPTER 2. NUTRITION AND LUPUS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and lupus.
Finding Nutrition Studies on Lupus The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “lupus” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on lupus: •
Lupus and the heart-joint connection. Source: Anonymous Johns-Hopkins-Med-Lett-Health-After-50. 2002 April; 14(2): 4-5 1042-1882
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Lupus: immunity gone awry. Source: Tsokos, George C Health-News. 2002 August; 8(8): 1-2 1081-5880
The following information is typical of that found when using the “Full IBIDS Database” to search for “lupus” (or a synonym): •
A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe systemic lupus erythematosus. Author(s): Division of Immunology & Rheumatology, University Medical Center, Stanford, USA.
[email protected] Source: van Vollenhoven, R F Park, J L Genovese, M C West, J P McGuire, J L Lupus. 1999; 8(3): 181-7 0961-2033
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A medical record of systemic lupus erythematosus. Author(s): Feidong County Hospital of Traditional Chinese Medicine, Anhui Province 231600. Source: Zhang, Y Cui, L Yang, X J-Tradit-Chin-Med. 2001 September; 21(3): 189-92 02546272
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Antineutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus: prevalence, antigen specificity, and clinical associations. Author(s): Laboratory of Clinical Immunology, University Hospital, Faculty of Medicine, Thracian University, Stara Zagora, Bulgaria. Source: Manolova, I Dancheva, M Halacheva, K Rheumatol-Int. 2001 July; 20(5): 197-204 0172-8172
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Antioxidants suppress mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE). Author(s): Division of Rheumatology, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. Source: Suwannaroj, S Lagoo, A Keisler, D McMurray, R W Lupus. 2001; 10(4): 258-65 0961-2033
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Association of vitamin D receptor gene BsmI polymorphisms in Chinese patients with systemic lupus erythematosus. Author(s): Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical College Hospital, Taiwan. Source: Huang, C M Wu, M C Wu, J Y Tsai, F J Lupus. 2002; 11(1): 31-4 0961-2033
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Bindarit prolongs survival and reduces renal damage in NZB/W lupus mice. Author(s): Angelini Ricerche, S. Palomba-Pomezia, Rome, Italy. Source: Guglielmotti, A Aquilini, L D'Onofrio, E Rosignoli, M T Milanese, C Pinza, M Clin-Exp-Rheumatol. 1998 Mar-April; 16(2): 149-54 0392-856X
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Biochemical characterization of 60S acidic ribosomal P proteins from porcine liver and the inhibition of their immunocomplex formation with sera from systemic lupus erythematosus (SLE) patients by glycyrrhizin in vitro. Author(s): Laboratory of Genetical Biochemistry, School of Allied Health Sciences, Kitasato Unsiversity, Sagamihara, Japan.
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Source: Maekawa, T Kosuge, S Karino, A Okano, T Ito, J Munakata, H Ohtsuki, K BiolPharm-Bull. 2000 January; 23(1): 27-32 0918-6158 •
Bone metabolism and bone mineral density of systemic lupus erythematosus at the time of diagnosis. Author(s): Medizinische Klinik III und Poliklinik, Justus-Liebig-Universitat Giessen, Germany. Source: Teichmann, J Lange, U Stracke, H Federlin, K Bretzel, R G Rheumatol-Int. 1999; 18(4): 137-40 0172-8172
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Bone mineral density in women with systemic lupus erythematosus. Author(s): Department of Obstetrics and Gynecology, Medical and Health Science Center, University of Debrecen, Hungary.
[email protected] Source: Bhattoa, H P Bettembuk, P Balogh, A Szegedi, G Kiss, E Clin-Rheumatol. 2002 May; 21(2): 135-41 0770-3198
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Bromocriptine treatment of systemic lupus erythematosus. Author(s): Department of Internal Medicine, The University of Missouri-Columbia, 65212, USA.
[email protected] Source: Walker, S E Lupus. 2001; 10(10): 762-8 0961-2033
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C4 deficiency state in antiphospholipid antibody-related recurrent preeclampsia evolving into systemic lupus erythematosus. Author(s): Hospital Central de Asturias, Oviedo-Asturias, Spain.
[email protected] Source: Queiro, R Weruaga, A Riestra, J L Rheumatol-Int. 2002 July; 22(3): 126-8 01728172
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Cerebral atrophy related to corticotherapy in systemic lupus erythematosus (SLE). Author(s): State University of Campinas, Sao Paulo, Brazil. Source: Zanardi, V A Magna, L A Costallat, L T Clin-Rheumatol. 2001; 20(4): 245-50 0770-3198
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Characterization of CD3+ CD4- CD8- (double negative) T cells in patients with systemic lupus erythematosus: production of IL-4. Author(s): Department of Immunology and Molecular Pathology, Royal Free and University College School of Medicine, London, UK. Source: Dean, G S Anand, A Blofeld, A Isenberg, D A Lydyard, P M Lupus. 2002; 11(8): 501-7 0961-2033
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Clinical and immunological manifestations in 134 Puerto Rican patients with systemic lupus erythematosus. Author(s): Department of Internal Medicine, Universidad Central del Caribe School of Medicine, Bayamon, Puerto Rico 00960-6032. Source: Vila, L M Mayor, A M Valentin, A H Garcia Soberal, M Vila, S Lupus. 1999; 8(4): 279-86 0961-2033
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Clinical trials in lupus nephritis. Author(s): State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Box 42, Brooklyn, NY 11203, USA.
[email protected] Source: Ginzler, E M Curr-Rheumatol-Repage 2001 June; 3(3): 199-204 1523-3774
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Combination treatment in autoimmune diseases: systemic lupus erythematosus. Author(s): Divisione di Nefrologia e Dialisi, Ospedale Maggiore IRCCS, Via della Commenda 15, 20122 Milan, Italy. Source: Moroni, G Della Casa Alberighi, O Ponticelli, C Springer-Semin-Immunopathol. 2001; 23(1-2): 75-89 0172-6641
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Dehydroepiandrosterone for the treatment of systemic lupus erythematosus. Author(s): Department of Rheumatology, Karolinska Hospital, 17176 Stockholm, Sweden. Source: van Vollenhoven, Ronald F Expert-Opin-Pharmacother. 2002 January; 3(1): 23-31 1465-6566
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Devic's neuromyelitis optica during pregnancy in a patient with systemic lupus erythematosus. Author(s): Service de medecine interne, Hopital Haut Leveque, Centre Hospitalier Universitaire de Bordeaux, France. Source: Bonnet, F Mercie, P Morlat, P Hocke, C Vergnes, C Ellie, E Viallard, J F Faure, I Pellegrin, J L Beylot, J Leng, B Lupus. 1999; 8(3): 244-7 0961-2033
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Dextran sulfate (Selesorb) plasma apheresis improves vascular changes in systemic lupus erythematosus. Author(s): Sektion Nieren- und Hochdruckkrankheiten der Medizinische Klinik und Poliklinik, Tubingen, Germany.
[email protected] Source: Braun, N Junger, M Klein, R Gutenberger, S Guagnin, M Risler, T Ther-Apher. 2002 December; 6(6): 471-7 1091-6660
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Diet and systemic lupus erythematosus: from mouse and monkey to woman? Source: Petri, M Lupus. 2001; 10(11): 775-7 0961-2033
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Diet may help lupus, MS, and arthritis, but caution is stressed. Source: Health-Values-Achieving-High-Level-Wellness. Thorofare : Charles B. Slack, Inc. July/August 1983. volume 7 (4) page 33-34. 0147-0353
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Diet modulates Th-1 and Th-2 cytokine production in the peripheral blood of lupusprone mice. Author(s): Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7874, USA. Source: Jolly, C A Fernandes, G J-Clin-Immunol. 1999 May; 19(3): 172-8 0271-9142
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Dietary polyunsaturated fatty acids decrease anti-dsDNA and anti-cardiolipin antibodies production in idiotype induced mouse model of systemic lupus erythematosus. Author(s): School of Nutritional Sciences, The Faculty of Agriculture, The Hebrew University of Jerusalem, Israel. Source: Reifen, R Blank, M Afek, A Kopilowiz, Y Sklan, D Gershwin, M E German, B Yoshida, S Shoenfeld, Y Lupus. 1998; 7(3): 192-7 0961-2033
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Direct transfer of p65 into T lymphocytes from systemic lupus erythematosus patients leads to increased levels of interleukin-2 promoter activity. Author(s): Department of Cellular Injury, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA. Source: Herndon, Thomas M Juang, Yuang Taung Solomou, Elena E Rothwell, Stephen W Gourley, Mark F Tsokos, George C Clin-Immunol. 2002 May; 103(2): 145-53 1521-6616
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Drug treatment of cutaneous lupus. Author(s): Royal Adelaide Hospital, Adelaide, South Australia, Australia. Source: Reid, C Am-J-Clin-Dermatol. 2000 Nov-December; 1(6): 375-9 1175-0561
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Drugs for discoid lupus erythematosus. Author(s): Dermatology, Groote Schuur Hospital, Observatory 7195, Cape Town, South Africa.
[email protected] Source: Jessop, S Whitelaw, D Jordaan, F Cochrane-Database-Syst-Revolume 2001; 1: CD002954 1469-493X
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Effect of mycophenolate mofetil on severity of nephritis and nitric oxide production in lupus-prone MRL/lpr mice. Author(s): Division of Nephrology, University Department of Medicine, Queen Mary Hospital, Hong Kong, Republic of China.
[email protected] Source: Lui, S L Tsang, R Wong, D Chan, K W Chan, T M Fung, P C Lai, K N Lupus. 2002; 11(7): 411-8 0961-2033
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Genetically determined interferon-gamma production influences the histological phenotype of lupus nephritis. Author(s): Department of Medicine and Biosystemic Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan. Source: Miyake, K Nakashima, H Akahoshi, M Inoue, Y Nagano, S Tanaka, Y Masutani, K Hirakata, H Gondo, H Otsuka, T Harada, M Rheumatology-(Oxford). 2002 May; 41(5): 518-24 1462-0324
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High prevalence of Trichinella nativa infection in wolf (Canis lupus) populations of Tvier and Smoliensk regions of European Russia. Author(s): Laboratory of Parasitology, Istituto Superiore di Sanita, viale Regina Elena 299, 00161 Rome, Italy. Source: Casulli, A La Rosa, G Amati, M Pozio, E Parasite. 2001 June; 8(2 Suppl): S88-9 1252-607X
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Histiocytic necrotizing lymphadenitis preceding systemic lupus erythematosus. Author(s): 2nd Department of Internal Medicine, University of Pecs, Medical Faculty, Hungary. Source: Komocsi, A Tovari, E Pajor, L Czirjak, L J-Eur-Acad-Dermatol-Venereol. 2001 September; 15(5): 476-80 0926-9959
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Infection in Thai patients with systemic lupus erythematosus: a review of hospitalized patients. Author(s): Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Source: Wongchinsri, J Tantawichien, T Osiri, M Akkasilpa, S Deesomchok, U J-MedAssoc-Thai. 2002 June; 85 Suppl 1: S34-9 0125-2208
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Influence of cholecalciferol (vitamin D3) on the course of experimental systemic lupus erythematosus in F1 (NZBxW) mice. Author(s): Disciplina de Imunologia-Departamento de Microbiologia, Imunologia, e Parasitologia, Universidade Federal de Sao Paulo-Escola Paulista de Medicina, Sao Paulo, Brazil.
[email protected] Source: Vaisberg, M W Kaneno, R Franco, M F Mendes, N F J-Clin-Lab-Anal. 2000; 14(3): 91-6 0887-8013
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Inhibition of intracellular peroxides and apoptosis of lymphocytes in lupus-prone B/W mice by dietary n-6 and n-3 lipids with calorie restriction. Author(s): University of Texas Health Science Center, Department of Medicine, San Antonio 78229-3900, USA. Source: Reddy Avula, C P Lawrence, R A Zaman, K Fernandes, G J-Clin-Immunol. 2002 July; 22(4): 206-19 0271-9142
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Juvenile parkinsonism as a manifestation of systemic lupus erythematosus: case report and review of the literature. Author(s): Servicio de Neurologia, Hospital Universitario Virgen Macarena, Sevilla, Spain.
[email protected] Source: Garcia Moreno, J M Chacon, J Mov-Disord. 2002 November; 17(6): 1329-35 08853185
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Lower limb pitting edema in systemic lupus erythematosus. Author(s): Department of Rheumatology and Hematology, Eberhard-Karls-University, Tubingen, Germany. Source: Gunaydin, I Daikeler, T Mohren, M Kanz, L Kotter, I Rheumatol-Int. 1999; 18(4): 159-60 0172-8172
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Lupus pregnancy: is heparin a risk factor for osteoporosis? Author(s): Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London, UK. Source: Ruiz Irastorza, G Khamashta, M A Nelson Piercy, C Hughes, G R Lupus. 2001; 10(9): 597-600 0961-2033
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Lupus vulgaris in a child following BCG immunization. Author(s): Department of Dermatology, Medical Faculty of Firat University, TR-23119, Elazig, Turkey.
[email protected] Source: Kokcam, I Kose, A Yekeler, H Doymaz, M Z Australas-J-Dermatol. 2001 November; 42(4): 275-7 0004-8380
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Lymphocyte apoptosis in systemic lupus erythematosus: relationships with Fas expression, serum soluble Fas and disease activity. Author(s): Department of Rheumatology and Immunology, Royal Victoria Hospital, Belfast, Ireland. Source: Courtney, P A Crockard, A D Williamson, K McConnell, J Kennedy, R J Bell, A L Lupus. 1999; 8(7): 508-13 0961-2033
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Management of chronic renal insufficiency in lupus nephritis: role of proteinuria, hypertension and dyslipidemia in the progression of renal disease. Author(s): Division of Nephrology, London Health Sciences Centre, Ontario, Canada. Source: Clark, W F Moist, L M Lupus. 1998; 7(9): 649-53 0961-2033
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Management of lupus erythematosus: recent insights. Author(s): Cedars-Sinai/UCLA School of Medicine, Los Angeles, California 90048, USA. Source: Wallace, D J Curr-Opin-Rheumatol. 2002 May; 14(3): 212-9 1040-8711
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Melioidosis in systemic lupus erythematosus: the importance of early diagnosis and treatment in patients from endemic areas. Author(s): Department of Rheumatology, Allergy and Immunology, Tan Tock Seng Hospital, Singapore. Source: Badsha, H Edwards, C J Chng, H H Lupus. 2001; 10(11): 821-3 0961-2033
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Membranous lupus nephritis in a renal allograft: response to mycophenolate mofetil therapy. Author(s): Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
[email protected] Source: Denton, M D Galvanek, E G Singh, A Sayegh, M H Am-J-Transplant. 2001 September; 1(3): 288-92 1600-6135
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Monitoring therapy with vitamin K antagonists in patients with lupus anticoagulant: effect on different tests for INR determination. Author(s): Department of Vascular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. Source: Bijsterveld, N R Middeldorp, S Berends, F Buller, H R J-Thromb-Thrombolysis. 2000 April; 9(3): 263-9 0929-5305
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Mycophenolate mofetil for systemic lupus erythematosus refractory to other immunosuppressive agents. Author(s): Lupus Research Unit, The Rayne Institute, Immunology Department, St Thomas' Hospital, London, UK.
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Source: Karim, M Y Alba, P Cuadrado, M J Abbs, I C D'Cruz, D P Khamashta, M A Hughes, G R V Rheumatology-(Oxford). 2002 August; 41(8): 876-82 1462-0324 •
Mycophenolate mofetil for the treatment of systemic lupus erythematosus: an open pilot trial. Author(s): Department of Medicine B, University of Munster, Munster, Germany.
[email protected] Source: Gaubitz, M Schorat, A Schotte, H Kern, P Domschke, W Lupus. 1999; 8(9): 731-6 0961-2033
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Natural medicine and nutritional therapy as an alternative treatment in systemic lupus erythematosus. Author(s): Masters Degree, Human Nutrition; working on completion of Doctor of Chiropractic degree, University of Bridgeport. Source: Patavino, T Brady, D M Altern-Med-Revolume 2001 October; 6(5): 460-71 10895159
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Neonatal lupus: clinical features, therapy, and pathogenesis. Author(s): Department of Dermatology, University of Colorado School of Medicine, 4200 East Ninth Avenue, Denver, CO 80262, USA.
[email protected] Source: Lee, L A Curr-Rheumatol-Repage 2001 October; 3(5): 391-5 1523-3774
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New therapies in systemic lupus erythematosus. Source: Solsky, Marilyn A Wallace, Daniel J Best-Pract-Res-Clin-Rheumatol. 2002 April; 16(2): 293-312 1521-6942
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Objective evidence of abnormal regional cerebral blood flow in patients with systemic lupus erythematosus on Tc-99m ECD brain SPECT. Author(s): Department of Neurology, China Medical College Hospital, Taichung, Taiwan. Source: Huang, W S Chiu, P Y Tsai, C H Kao, A Lee, C C Rheumatol-Int. 2002 September; 22(5): 178-81 0172-8172
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Osteopenia in young hypogonadal women with systemic lupus erythematosus receiving chronic steroid therapy: a randomized controlled trial comparing calcitriol and hormonal replacement therapy. Author(s): Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China. Source: Kung, A W Chan, T M Lau, C S Wong, R W Yeung, S S Rheumatology-(Oxford). 1999 December; 38(12): 1239-44 1462-0324
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Outcome of neuropsychiatric systemic lupus erythematosus within a defined Swedish population: increased morbidity but low mortality. Author(s): Department of Rheumatology and. Department of Neurology, University Hospital of Lund, Lund, Sweden. Source: Jonsen, A Bengtsson, A A Nived, O Ryberg, B Sturfelt, G Rheumatology(Oxford). 2002 November; 41(11): 1308-12 1462-0324
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Oxidative stress in systemic lupus erythematosus and allied conditions with vascular involvement. Author(s): Department of Haematology, St Thomas' Hospital, London, UK. Source: Ames, P R Alves, J Murat, I Isenberg, D A Nourooz Zadeh, J Rheumatology(Oxford). 1999 June; 38(6): 529-34 1462-0324
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Predominance of IgG1 and IgG3 subclasses of autoantibodies to neutrophil cytoplasmic antigens in patients with systemic lupus erythematosus. Author(s): Laboratory of Clinical Immunology, University Hospital, Faculty of Medicine, Thracian University, Stara Zagora, Bulgaria. Source: Manolova, I Dancheva, M Halacheva, K Rheumatol-Int. 2002 April; 21(6): 227-33 0172-8172
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Prospective measure of serum 3-nitrotyrosine levels in systemic lupus erythematosus: correlation with disease activity. Author(s): Department of Medicine, Medical University of South Carolina, Charleston 29425, USA. Source: Oates, J C Christensen, E F Reilly, C M Self, S E Gilkeson, G S Proc-Assoc-AmPhysicians. 1999 Nov-December; 111(6): 611-21 1081-650X
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Protective effect of hydroxychloroquine in systemic lupus erythematosus. Prospective long-term study of an Israeli cohort. Author(s): Rheumatology Unit, Rabin Medical Center, Petah Tiqva, Israel.
[email protected] Source: Molad, Y Gorshtein, A Wysenbeek, A J Guedj, D Majadla, R Weinberger, A Amit Vazina, M Lupus. 2002; 11(6): 356-61 0961-2033
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Pulmonary diffusion capacity in patients with systemic lupus erythematosus. Author(s): Department of Medicine (II), Niigata University School of Medicine, Niigata, Japan.
[email protected] Source: Nakano, Masaaki Hasegawa, Hisashi Takada, Toshinori Ito, Satoshi Muramatsu, Yoshiyuki Satoh, Makoto Suzuki, Eiichi Gejyo, Fumitake Respirology. 2002 March; 7(1): 45-9 1323-7799
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Pulmonary hypertension secondary to systemic lupus erythematosus: prolonged survival following treatment with intermittent low dose iloprost. Author(s): University Department of Medicine, Queen Mary Hospital, Hong Kong, Hong Kong. Source: Mok, M Y Tse, H F Lau, C S Lupus. 1999; 8(4): 328-31 0961-2033
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Recruitment strategies in superiority trials in SLE: lessons from the study of methotrexate in lupus erythematosus (SMILE). Author(s): Division of Clinical Epidemiology. Source: Ferland, D Fortin, P R Lupus. 1999; 8(8): 606-11 0961-2033
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Sustained normalization of cerebral blood-flow after iloprost therapy in a patient with neuropsychiatric systemic lupus erythematosus. Author(s): Center for Systemic Rheumatic Diseases, Cagliari, Italy.
[email protected] Source: Mathieu, A Sanna, G Mameli, A Pinna, C Vacca, A Cauli, A Passiu, G Piga, M Lupus. 2002; 11(1): 52-6 0961-2033
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Systemic lupus erythematosus complicated with cerebral venous sinus thrombosis : a report of two cases. Author(s): Department of Internal Medicine, School of Medicine, Kyungpook National University, Taegu, Korea. Source: Lee, M K Kim, J H Kang, H R Rho, H J Nam, E J Kim, S W Kang, Y M Lee, J M Kim, N S J-Korean-Med-Sci. 2001 June; 16(3): 351-4 1011-8934
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Systemic lupus erythematosus presenting earlier as retinal vaso-occlusion. Author(s): Department of Internal Medicine, Catholic University of Daegu, School of Medicine, Korea.
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Source: Song, Y H Kim, C G Kim, S D Kim, Y Y Choe, J Y Korean-J-Intern-Med. 2001 September; 16(3): 210-3 0494-4712 •
Ten years' experience of aortic aneurysm associated with systemic lupus erythematosus. Author(s): Division of Vascular Surgery, Department of Surgery, Japan. Source: Ohara, N Miyata, T Kurata, A Oshiro, H Sato, O Shigematsu, H Eur-J-VascEndovasc-Surg. 2000 March; 19(3): 288-93 1078-5884
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The safety and efficacy of MMF in lupus nephritis: a pilot study. Author(s): Centre for Nephrology, Royal Free and University College Medical School, University College London, UK.
[email protected] Source: Kingdon, E J McLean, A G Psimenou, E Davenport, A Powis, S H Sweny, P Burns, A Lupus. 2001; 10(9): 606-11 0961-2033
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Treatment options for juvenile-onset systemic lupus erythematosus. Author(s): Service of Rheumatology, General University Hospital Gregorio Mara, Complutense University of Madrid, Madrid, Spain.
[email protected] Source: Carreno, L Lopez Longo, F J Gonzalez, C M Monteagudo, I Paediatr-Drugs. 2002; 4(4): 241-56 1174-5878
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Ulcerating plantar keratoderma in association with systemic lupus erythematosus. Author(s): Department of Dermatology, Henry Ford Health System, Detroit, Michigan 48202-2608, USA. Source: Grossberg, E B Scherschun, L Fivenson, D P Lupus. 2001; 10(9): 650-2 0961-2033
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Unilateral tumid lupus erythematosus. Author(s):
[email protected] Source: Pacheco, T R Spates, S T Lee, L A Lupus. 2002; 11(6): 388-91 0961-2033
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Update on the treatment of systemic lupus erythematosus: therapeutic highlights from the Sixth International Lupus Conference. Author(s): Rheumatic Diseases Unit, Department of Medicine D, Soroka Medical Center, Faculty Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
[email protected] Source: Abu Shakra, Mahmoud Buskila, Dan Isr-Med-Assoc-J. 2002 January; 4(1): 71-3 1565-1088
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Urinary glycosaminoglycans in patients with systemic lupus erythematosus. Author(s): Department of Physiological, Biochemical and Cellular Science, University of Sassari, Sassari, Italy. Source: De Muro, P Faedda, R Formato, M Re, F Satta, A Cherchi, G M Carcassi, A ClinExp-Rheumatol. 2001 Mar-April; 19(2): 125-30 0392-856X
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Vanderbilt morning report. Idiopathic polymyositis as the initial manifestation of lupus erythematosus. Author(s): Vanderbilt Medical Center, Nashville, USA. Source: Loss, C Aronoff, D Tenn-Med. 2000 August; 93(8): 300-1 1088-6222
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to lupus; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation:
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Vitamins Pantothenic Acid Source: Healthnotes, Inc. www.healthnotes.com Vitamin A Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B complex Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,962,00.html Vitamin C Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html Vitamin E Source: Healthnotes, Inc. www.healthnotes.com Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,906,00.html
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Minerals Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Beta-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com D-Alpha-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Delta-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Iron Source: Healthnotes, Inc. www.healthnotes.com
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Magnesium Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10055,00.html Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html Zinc/copper Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,938,00.html •
Food and Diet Flaxseeds Source: Healthnotes, Inc. www.healthnotes.com Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Omega-3 fatty acids Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,992,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND LUPUS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to lupus. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to lupus and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “lupus” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to lupus: •
A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites, and suppresses lupus in MRL-lpr mice. Author(s): Kelley VE, Ferretti A, Izui S, Strom TB. Source: Journal of Immunology (Baltimore, Md. : 1950). 1985 March; 134(3): 1914-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3918111&dopt=Abstract
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A medical record of systemic lupus erythematosus. Author(s): Zhang Y, Cui L, Yang X. Source: J Tradit Chin Med. 2001 September; 21(3): 189-92. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789323&dopt=Abstract
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A multidimensional approach to pain relief: case report of a patient with Systemic Lupus Erythematosus. Author(s): Smith SJ, Balaban AB.
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Source: Int J Clin Exp Hypn. 1983 April; 31(2): 72-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6832860&dopt=Abstract •
A novel treatment for lupus nephritis: lignan precursor derived from flax. Author(s): Clark WF, Muir AD, Westcott ND, Parbtani A. Source: Lupus. 2000; 9(6): 429-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10981647&dopt=Abstract
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A rapid screen for lupus anticoagulant with good discrimination from oral anticoagulants, congenital factor deficiency and heparin, is provided by comparing a sensitive and an insensitive APTT reagent. Author(s): Brancaccio V, Ames PR, Glynn J, Iannaccone L, Mackie IJ. Source: Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis. 1997 April; 8(3): 155-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9167015&dopt=Abstract
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Abnormal prothrombin crossed-immunoelectrophoresis in patients with lupus inhibitors. Author(s): Edson JR, Vogt JM, Hasegawa DK. Source: Blood. 1984 October; 64(4): 807-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6434005&dopt=Abstract
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Acute leukemia with features of systemic lupus erythematosus. Author(s): Saulsbury FT, Sabio H, Conrad D, Kesler RW, Levien MG. Source: The Journal of Pediatrics. 1984 July; 105(1): 57-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6610737&dopt=Abstract
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Acute renal failure caused by 'cat's claw' herbal remedy in a patient with systemic lupus erythematosus. Author(s): Hilepo JN, Bellucci AG, Mossey RT. Source: Nephron. 1997; 77(3): 361. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9375835&dopt=Abstract
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Adapting the systemic lupus erythematosus self-help (SLESH) course for Latino SLE patients. Author(s): Robbins L, Allegrante JP, Paget SA. Source: Arthritis Care and Research : the Official Journal of the Arthritis Health Professions Association. 1993 June; 6(2): 97-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8399433&dopt=Abstract
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All about lupus. Author(s): Brain E.
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Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 1989 April 29; 3(31): 41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2498711&dopt=Abstract •
Animal models of cutaneous lupus erythematosus and lupus erythematosus photosensitivity. Author(s): Furukawa F. Source: Lupus. 1997; 6(2): 193-202. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9061668&dopt=Abstract
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Anti-DNA antibodies in the urine of lupus nephritis patients. Author(s): Macanovic M, Hogarth MB, Lachmann PJ. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1999 June; 14(6): 1418-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10383001&dopt=Abstract
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Assessment of myocardial perfusion and function in childhood systemic lupus erythematosus. Author(s): Gazarian M, Feldman BM, Benson LN, Gilday DL, Laxer RM, Silverman ED. Source: The Journal of Pediatrics. 1998 January; 132(1): 109-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9470010&dopt=Abstract
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Association of complement C4 and HLA-DR alleles with systemic lupus erythematosus in Koreans. Author(s): Hong GH, Kim HY, Takeuchi F, Nakano K, Yamada H, Matsuta K, Han H, Tokunaga K, Ito K, Park KS. Source: The Journal of Rheumatology. 1994 March; 21(3): 442-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7911834&dopt=Abstract
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Auriculo-acupuncture in 15 cases of discoid lupus erythematosus. Author(s): Chen YS, Hu XE. Source: J Tradit Chin Med. 1985 December; 5(4): 261-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3834238&dopt=Abstract
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Autoimmune thrombocytopenia in pediatric systemic lupus erythematosus: alternative therapeutic modalities. Author(s): Lipnick RN, Tsokos GC, Bray GL, White PH. Source: Clin Exp Rheumatol. 1990 May-June; 8(3): 315-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1696192&dopt=Abstract
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Beneficial effect of eicosapentaenoic and docosahexaenoic acids in the management of systemic lupus erythematosus and its relationship to the cytokine network. Author(s): Das UN. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 1994 September; 51(3): 207-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7824535&dopt=Abstract
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Blast crisis of chronic myelogenous leukemia in long-lasting systemic lupus erythematosus: regression of both diseases after autologous bone marrow transplantation. Author(s): Meloni G, Capria S, Vignetti M, Mandelli F, Modena V. Source: Blood. 1997 June 15; 89(12): 4659. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9192793&dopt=Abstract
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Blood chemistry in deficiency of kidney-yin and deficiency of kidney-yang types of subacute systemic lupus erythematosus. Author(s): Zhang FS, Sun P. Source: J Tradit Chin Med. 1985 December; 5(4): 265-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3834240&dopt=Abstract
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Brainstem auditory evoked potentials with increased stimulus rate in patients suffering from systemic lupus erythematosus. Author(s): Fradis M, Podoshin L, Ben-David J, Statter P, Pratt H, Nahir M. Source: The Laryngoscope. 1989 March; 99(3): 325-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2918803&dopt=Abstract
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Bullous eruption in a patient with systemic lupus erythematosus. Author(s): Lewis D, Logas DB, Wojciechowski J, Friberg C. Source: Journal of the American Academy of Dermatology. 1998 June; 38(6 Pt 1): 1013-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9632025&dopt=Abstract
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C1 subcomponent complexes and C2 cleavage in active systemic lupus erythematosus. Author(s): Jonsson H, Sjoholm AG, Martensson U, Laurell AB, Sturfelt G. Source: Complement Inflamm. 1991; 8(1): 1-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2049932&dopt=Abstract
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C1q solid-phase radioimmunoassay: binding properties of solid-phase C1q and evidence that C1q-binding IgG complexes in systemic lupus erythematosus are not bound to endogenous C1q. Author(s): Uwatoko S, Aotsuka S, Okawa M, Egusa Y, Yokohari R, Aizawa C, Suzuki K. Source: Journal of Immunological Methods. 1984 October 12; 73(1): 67-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6436382&dopt=Abstract
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Calciphylaxis in a patient with end-stage renal disease secondary to systemic lupus erythematosus associated with acral gangrene and mesenteric ischemia. Author(s): Igaki N, Moriguchi R, Hirota Y, Sakai M, Akiyama H, Tamada F, Oimomi M, Goto T. Source: Intern Med. 2001 December; 40(12): 1232-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11813850&dopt=Abstract
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Central nervous system involvement in systemic lupus erythematosus patients without overt neuropsychiatric manifestations. Author(s): Sabbadini MG, Manfredi AA, Bozzolo E, Ferrario L, Rugarli C, Scorza R, Origgi L, Vanoli M, Gambini O, Vanzulli L, Croce D, Campana A, Messa C, Fazio F, Tincani A, Anzola G, Cattaneo R, Padovani A, Gasparotti R, Gerli R, Quartesan R, Piccirilli M, Farsi A, Emmi E, Passaleva A, et al. Source: Lupus. 1999; 8(1): 11-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10025594&dopt=Abstract
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Central nervous system lupus: concomitant occurrence of myelopathy and cognitive dysfunction. Author(s): Stahl HD, Ettlin TH, Plohmann A, Radu EW, Muller-Brand J, Steiger U, Tyndall A. Source: Clinical Rheumatology. 1994 June; 13(2): 273-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8088073&dopt=Abstract
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Cerebral imaging by magnetic resonance imaging and single photon emission computed tomography in systemic lupus erythematosus with central nervous system involvement. Author(s): Oku K, Atsumi T, Furukawa S, Horita T, Sakai Y, Jodo S, Amasaki Y, Ichikawa K, Amengual O, Koike T. Source: Rheumatology (Oxford, England). 2003 June; 42(6): 773-7. Epub 2003 March 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730538&dopt=Abstract
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Cerebral lupus. Author(s): Mitchell I, Webb M, Hughes R, Stewart J. Source: Lancet. 1994 March 5; 343(8897): 579-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7906333&dopt=Abstract
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Chorea, eosinophilia, and lupus anticoagulant associated with acute lymphoblastic leukemia. Author(s): Schiff DE, Ortega JA. Source: Pediatric Neurology. 1992 November-December; 8(6): 466-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1476578&dopt=Abstract
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Chromium-51 ethylenediamine tetraacetic acid glomerular filtration rate: a better predictor than glomerular filtration rate calculated by the Cockcroft-Gault formula
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for renal involvement in systemic lupus erythematosus patients. Author(s): Godfrey T, Cuadrado MJ, Fofi C, Abbs I, Khamashta MA, Nunan T, Hughes GR. Source: Rheumatology (Oxford, England). 2001 March; 40(3): 324-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11285381&dopt=Abstract •
Clinical observations on Tripterygium wilfordii in treatment of 26 cases of discoid lupus erythematosus. Author(s): Qin WZ, Zhu GD, Yang SM, Han KY, Wang J. Source: J Tradit Chin Med. 1983 June; 3(2): 131-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6555446&dopt=Abstract
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Clinical studies on the significance of DNA:anti-DNA complexes in the systemic circulation and cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus. Author(s): Carr RI, Harbeck RJ, Hoffman AA, Pirofsky B, Bardana EJ. Source: The Journal of Rheumatology. 1975 June; 2(2): 184-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=807729&dopt=Abstract
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Clinical trials in lupus nephritis. Author(s): Ginzler EM. Source: Curr Rheumatol Rep. 2001 June; 3(3): 199-204. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11352788&dopt=Abstract
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Complement fixing immune complexes containing antinuclear antibodies in patients with systemic lupus erythematosus. Author(s): Budd JJ 3rd, Moore TL, Osborn TG. Source: The Journal of Rheumatology. 1988 February; 15(2): 247-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3258914&dopt=Abstract
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Complexes of serum amyloid P component and DNA in serum from healthy individuals and systemic lupus erythematosus patients. Author(s): Sorensen IJ, Holm Nielsen E, Schroder L, Voss A, Horvath L, Svehag SE. Source: Journal of Clinical Immunology. 2000 November; 20(6): 408-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11202230&dopt=Abstract
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Daily psychosocial stressors interfere with the dynamics of urine neopterin in a patient with systemic lupus erythematosus: an integrative single-case study. Author(s): Schubert C, Lampe A, Rumpold G, Fuchs D, Konig P, Chamson E, Schussler G. Source: Psychosomatic Medicine. 1999 November-December; 61(6): 876-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10593641&dopt=Abstract
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Decreased bone mineral density in female patients with systemic lupus erythematosus after long-term administration of Tripterygium Wilfordii Hook. F. Author(s): Huang L, Feng S, Wang H. Source: Chin Med J (Engl). 2000 February; 113(2): 159-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775543&dopt=Abstract
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Decreased pro-inflammatory cytokines and increased antioxidant enzyme gene expression by omega-3 lipids in murine lupus nephritis. Author(s): Chandrasekar B, Fernandes G. Source: Biochemical and Biophysical Research Communications. 1994 April 29; 200(2): 893-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8179624&dopt=Abstract
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Detection of immune complexes in unheated sera by modified 125I-Clq binding test. Effect of heating on the binding of Clq by immune complexes and application of the test to systemic lupus erythematosus. Author(s): Zubler RH, Lange G, Lambert PH, Miescher PA. Source: Journal of Immunology (Baltimore, Md. : 1950). 1976 January; 116(1): 232-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1245740&dopt=Abstract
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Diet and systemic lupus erythematosus: from mouse and monkey to woman? Author(s): Petri M. Source: Lupus. 2001; 10(11): 775-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789485&dopt=Abstract
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Dietary conjugated linoleic acid protects against end stage disease of systemic lupus erythematosus in the NZB/W F1 mouse. Author(s): Yang M, Pariza MW, Cook ME. Source: Immunopharmacology and Immunotoxicology. 2000 August; 22(3): 433-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10946824&dopt=Abstract
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Dietary fish oil and the severity of symptoms in patients with systemic lupus erythematosus. Author(s): Walton AJ, Snaith ML, Locniskar M, Cumberland AG, Morrow WJ, Isenberg DA. Source: Annals of the Rheumatic Diseases. 1991 July; 50(7): 463-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1877851&dopt=Abstract
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Dietary omega-3 lipids delay the onset and progression of autoimmune lupus nephritis by inhibiting transforming growth factor beta mRNA and protein expression. Author(s): Chandrasekar B, Troyer DA, Venkatraman JT, Fernandes G.
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Source: Journal of Autoimmunity. 1995 June; 8(3): 381-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7575999&dopt=Abstract •
Dietary polyunsaturated fatty acids decrease anti-dsDNA and anti-cardiolipin antibodies production in idiotype induced mouse model of systemic lupus erythematosus. Author(s): Reifen R, Blank M, Afek A, Kopilowiz Y, Sklan D, Gershwin ME, German B, Yoshida S, Shoenfeld Y. Source: Lupus. 1998; 7(3): 192-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9607643&dopt=Abstract
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Diffuse central nervous system lupus involving white matter, basal ganglia, thalami and brainstem. Author(s): Shibata M, Kibe T, Fujimoto S, Ishikawa T, Murakami M, Ichiki T, Wada Y. Source: Brain & Development. 1999 July; 21(5): 337-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10413022&dopt=Abstract
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Early hyperbaric oxygen therapy attenuates disease severity in lupus-prone autoimmune (NZB x NZW) F1 mice. Author(s): Chen SY, Chen YC, Wang JK, Hsu HP, Ho PS, Chen YC, Sytwu HK. Source: Clinical Immunology (Orlando, Fla.). 2003 August; 108(2): 103-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921756&dopt=Abstract
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Effect of a culturally sensitive cholesterol lowering diet program on lipid and lipoproteins, body weight, nutrient intakes, and quality of life in patients with systemic lupus erythematosus. Author(s): Shah M, Kavanaugh A, Coyle Y, Adams-Huet B, Lipsky PE. Source: The Journal of Rheumatology. 2002 October; 29(10): 2122-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375321&dopt=Abstract
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Effect of acetylsalicylic acid on renal function in systemic lupus erythematosus. Author(s): Rasmussen S, Petersen J, Nielsen IL, Christensen P, Hilden T. Source: European Journal of Clinical Pharmacology. 1982; 23(6): 505-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7160418&dopt=Abstract
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Effect of vegetarian diet on systemic lupus erythematosus. Author(s): Shigemasa C, Tanaka T, Mashiba H. Source: Lancet. 1992 May 9; 339(8802): 1177. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1349403&dopt=Abstract
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Evaluation of the Japanese-Chinese herbal medicine, kampo, for the treatment of lupus dermatoses in autoimmune prone MRL/Mp-lpr/lpr mice. Author(s): Kanauchi H, Imamura S, Takigawa M, Furukawa F.
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Source: The Journal of Dermatology. 1994 December; 21(12): 935-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7868765&dopt=Abstract •
Fatigue in systemic lupus erythematosus: a randomized controlled trial of exercise. Author(s): Tench CM, McCarthy J, McCurdie I, White PD, D'Cruz DP. Source: Rheumatology (Oxford, England). 2003 September; 42(9): 1050-4. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730519&dopt=Abstract
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Favorable response to intravenous methylprednisolone and cyclophosphamide in children with severe neuropsychiatric lupus. Author(s): Baca V, Lavalle C, Garcia R, Catalan T, Sauceda JM, Sanchez G, Martinez I, Ramirez ML, Marquez LM, Rojas JC. Source: The Journal of Rheumatology. 1999 February; 26(2): 432-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9972981&dopt=Abstract
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Filtration fraction: an index of renal disease activity in patients with systemic lupus erythematosus. Author(s): Favre H, Miescher PA. Source: Proc Eur Dial Transplant Assoc Eur Ren Assoc. 1985; 21: 717-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3991566&dopt=Abstract
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Flaxseed in lupus nephritis: a two-year nonplacebo-controlled crossover study. Author(s): Clark WF, Kortas C, Heidenheim AP, Garland J, Spanner E, Parbtani A. Source: Journal of the American College of Nutrition. 2001 April; 20(2 Suppl): 143-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349937&dopt=Abstract
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Hysterical contracture complicating hemiplegia in a patient with systemic lupus erythematosus, activated in pregnancy. Author(s): Pryse-Phillips W, Yorkston NJ. Source: Guys Hosp Rep. 1965; 114(3): 239-47. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5837862&dopt=Abstract
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Immunosuppression and immunomodulation of experimental models of systemic lupus erythematosus and antiphospholipid syndrome. Author(s): Shoenfeld Y, Krause I. Source: Transplantation Proceedings. 1996 December; 28(6): 3096-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8962199&dopt=Abstract
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Improved survival in murine lupus as the result of selenium supplementation. Author(s): O'Dell JR, McGivern JP, Kay HD, Klassen LW.
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Source: Clinical and Experimental Immunology. 1988 August; 73(2): 322-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3263235&dopt=Abstract •
Improvement in lupus nephritis following treatment with a Chinese herbal preparation. Author(s): Yap HK, Ang SG, Lai YH, Ramgolam V, Jordan SC. Source: Archives of Pediatrics & Adolescent Medicine. 1999 August; 153(8): 850-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437759&dopt=Abstract
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Improving lupus knowledge. Author(s): Rossiter R. Source: Australian Nursing Journal (July 1993). 2001 September; 9(3): 39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908120&dopt=Abstract
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Influence of dietary fatty acids on the composition of plasma fatty acids in the tundra wolf (Canis lupus tundrarum). Author(s): Shultz TD, Ferguson JH. Source: Comp Biochem Physiol A. 1974 November 1; 49(3A): 575-81. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4154062&dopt=Abstract
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Inhibition of intracellular peroxides and apoptosis of lymphocytes in lupus-prone B/W mice by dietary n-6 and n-3 lipids with calorie restriction. Author(s): Reddy Avula CP, Lawrence RA, Zaman K, Fernandes G. Source: Journal of Clinical Immunology. 2002 July; 22(4): 206-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12148595&dopt=Abstract
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Insecticide-induced lupus erythematosus. Author(s): Curtis CF. Source: International Journal of Dermatology. 1996 January; 35(1): 74-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8838938&dopt=Abstract
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Intestinal permeability test in systemic lupus erythematosus. Author(s): Wang SJ, Kao CH, Chen DU, Lan JL. Source: Zhonghua Yi Xue Za Zhi (Taipei). 1992 January; 49(1): 29-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1312382&dopt=Abstract
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Living with Lupus. Author(s): Hubscher O. Source: The Journal of Rheumatology. 2002 July; 29(7): 1574; Author Reply 1574. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136924&dopt=Abstract
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Lupus clients assisting one another: a model for supportive services. Author(s): Kroll CJ. Source: Rehabilitation Nursing : the Official Journal of the Association of Rehabilitation Nurses. 1987 September-October; 12(5): 239-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3671868&dopt=Abstract
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Lupus erythematosus and nutrition: a review of the literature. Author(s): Brown AC. Source: Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation. 2000 October; 10(4): 170-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11070144&dopt=Abstract
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Lupus support and awareness in the Republic of Ireland. Author(s): Corcoran D, Wall JG. Source: Ir Med J. 2000 March-April; 93(2): 54-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11037252&dopt=Abstract
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Lupus-erythematosus-like eruption induced by Trichophyton mentagrophytes infection. Author(s): Boralevi F, Leaute-Labreze C, Roul S, Couprie B, Taieb A. Source: Dermatology (Basel, Switzerland). 2003; 206(4): 303-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771470&dopt=Abstract
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Measurement of deoxyribonuclease I (DNase) in the serum and urine of systemic lupus erythematosus (SLE)-prone NZB/NZW mice by a new radial enzyme diffusion assay. Author(s): Macanovic M, Lachmann PJ. Source: Clinical and Experimental Immunology. 1997 May; 108(2): 220-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9158089&dopt=Abstract
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Natural medicine and nutritional therapy as an alternative treatment in systemic lupus erythematosus. Author(s): Patavino T, Brady DM. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2001 October; 6(5): 460-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11703166&dopt=Abstract
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Neuropsychiatric systemic lupus erythematosus before and after immunosuppressive treatment: a FDG PET study. Author(s): Otte A, Weiner SM, Hoegerle S, Wolf R, Juengling FD, Peter HH, Nitzsche EU.
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Source: Lupus. 1998; 7(1): 57-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9493152&dopt=Abstract •
Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow. Author(s): Waterloo K, Omdal R, Sjoholm H, Koldingsnes W, Jacobsen EA, Sundsfjord JA, Husby G, Mellgren SI. Source: Journal of Neurology. 2001 July; 248(7): 595-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518002&dopt=Abstract
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New environmental agents associated with lupus-like disorders. Author(s): Love LA. Source: Lupus. 1994 December; 3(6): 467-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7704003&dopt=Abstract
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Omega-3 fatty acid dietary supplementation in systemic lupus erythematosus. Author(s): Clark WF, Parbtani A, Huff MW, Reid B, Holub BJ, Falardeau P. Source: Kidney International. 1989 October; 36(4): 653-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2811063&dopt=Abstract
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Omega-3 fatty acid supplementation in clinical and experimental lupus nephritis. Author(s): Clark WF, Parbtani A. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1994 May; 23(5): 644-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8172205&dopt=Abstract
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Outcome in African-American children of neuropsychiatric lupus and lupus nephritis. Author(s): Vyas S, Hidalgo G, Baqi N, Von Gizyki H, Singh A. Source: Pediatric Nephrology (Berlin, Germany). 2002 January; 17(1): 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11793134&dopt=Abstract
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Oxidant stress, anti-oxidants and essential fatty acids in systemic lupus erythematosus. Author(s): Mohan IK, Das UN. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 1997 March; 56(3): 1938. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9089797&dopt=Abstract
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Paclitaxel reduces anti-dsDNA antibody titer and BUN, prolonging survival in murine lupus. Author(s): Song YW, Kim HA, Baek HJ, Lee EB, Chung ES, Hong KM.
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Source: International Journal of Immunopharmacology. 1998 November; 20(11): 669-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9848398&dopt=Abstract •
Paraneoplastic subacute cutaneous lupus erythematosus: report of a case associated with cancer of the lung. Author(s): Brenner S, Golan H, Gat A, Bialy-Golan A. Source: Dermatology (Basel, Switzerland). 1997; 194(2): 172-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9094469&dopt=Abstract
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Parkinsonian syndrome complicating systemic lupus erythematosus. Author(s): Shahar E, Goshen E, Tauber Z, Lahat E. Source: Pediatric Neurology. 1998 May; 18(5): 456-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9650692&dopt=Abstract
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Patient management of systemic lupus erythematosus. Author(s): White JF, Ziegler GL. Source: Crit Care Update. 1980 August; 7(8): 5-15. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6901660&dopt=Abstract
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Patterns of change over time in learned response to chronic illness among participants in a systemic lupus erythematosus self-help course. Author(s): Braden CJ. Source: Arthritis Care and Research : the Official Journal of the Arthritis Health Professions Association. 1991 December; 4(4): 158-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11188603&dopt=Abstract
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Periorbital heliotrope oedema as the only initial clinical manifestation of systemic lupus erythematosus in a primigravida. Author(s): Dai YS, Chiu HC. Source: The British Journal of Dermatology. 2000 September; 143(3): 679-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10971372&dopt=Abstract
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Plasma concentration of IL-6 in systemic lupus erythematosus; an indicator of disease activity? Author(s): Spronk PE, ter Borg EJ, Limburg PC, Kallenberg CG. Source: Clinical and Experimental Immunology. 1992 October; 90(1): 106-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1395090&dopt=Abstract
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Prednisolone non-compliance and its related factors in patients with systemic lupus erythematosus. Author(s): Lin WS, Yang WS, Lin HY.
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Source: Zhonghua Yi Xue Za Zhi (Taipei). 1995 October; 56(4): 244-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8548666&dopt=Abstract •
Preparation of DNA-immobilized immunoadsorbent for treatment of systemic lupus erythematosus. Author(s): Zhu B, Iwata H, Kong D, Yu Y, Kato K, Ikada Y. Source: Journal of Biomaterials Science. Polymer Edition. 1999; 10(3): 341-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10189102&dopt=Abstract
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Progressive thrombosis after treatment of diffuse large cell non-Hodgkin's lymphoma and concomitant lupus anticoagulant. Author(s): Keung YK, Cobos E, Meyerrose GE, Roberson GH. Source: Leukemia & Lymphoma. 1996 January; 20(3-4): 341-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8624478&dopt=Abstract
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Pycnogenol efficacy in the treatment of systemic lupus erythematosus patients. Author(s): Stefanescu M, Matache C, Onu A, Tanaseanu S, Dragomir C, Constantinescu I, Schonlau F, Rohdewald P, Szegli G. Source: Phytotherapy Research : Ptr. 2001 December; 15(8): 698-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746863&dopt=Abstract
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Quality of life in systemic lupus erythematosus. Author(s): Lash AA. Source: Applied Nursing Research : Anr. 1998 August; 11(3): 130-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9757613&dopt=Abstract
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Quantitative cerebral perfusion SPECT in systemic lupus erythematosus with severe central nervous involvement--before and after methylprednisolone pulse therapy. Author(s): You DL, Tzen KY, Kao PF, Tsai MF. Source: Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging. 1998 January; 8(1): 55-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9442596&dopt=Abstract
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Rasmussen's encephalitis followed by lupus erythematosus. Author(s): Lascelles K, Dean AF, Robinson RO. Source: Developmental Medicine and Child Neurology. 2002 August; 44(8): 572-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206625&dopt=Abstract
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Reflex seizures as initial manifestations of systemic lupus erythematosus in childhood. Author(s): Brinciotti M, Ferrucci G, Trasatti G, Priori R, Squilloni E, Valesini G.
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Source: Lupus. 1993 August; 2(4): 281-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8268979&dopt=Abstract •
Resolution of severe lupus nephritis associated with Tripterygium wilfordii hook F ingestion. Author(s): Kao NL, Richmond GW, Moy JN. Source: Arthritis and Rheumatism. 1993 December; 36(12): 1751-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8250996&dopt=Abstract
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Reversal of brain dysfunction with UV-A1 irradiation in a patient with systemic lupus. Author(s): Menon Y, McCarthy K, McGrath H Jr. Source: Lupus. 2003; 12(6): 479-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873051&dopt=Abstract
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Scabies mimicking systemic lupus erythematosus. Author(s): Bastian HM, Lindgren AM, Alarcon GS. Source: The American Journal of Medicine. 1997 March; 102(3): 305-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9217603&dopt=Abstract
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Serial estimation of anti-RNP antibody titers in systemic lupus erythematosus, mixed connective tissue disease and rheumatoid arthritis. Author(s): Nishikai M, Okano Y, Mukohda Y, Sato A, Ito M. Source: J Clin Lab Immunol. 1984 January; 13(1): 15-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6609234&dopt=Abstract
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Serial single photon emission computed tomography imaging in patients with cerebral lupus during acute exacerbation and after treatment. Author(s): Huang JL, Yeh KW, You DL, Hsieh KH. Source: Pediatric Neurology. 1997 July; 17(1): 44-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9308975&dopt=Abstract
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Severe arthralgia and myalgia due to high-dose methylprednisolone pulse therapy cured by potassium infusion in a patient with diffuse proliferative lupus nephritis. Author(s): Odabas AR, Cetinkaya R, Selcuk Y, Kaya H. Source: Nephron. 2001 January; 87(1): 95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11174035&dopt=Abstract
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Single photon emission computed tomography dual isotope myocardial perfusion imaging in women with systemic lupus erythematosus. II. Predictive factors for perfusion abnormalities. Author(s): Bruce IN, Gladman DD, Ibanez D, Urowitz MB.
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Source: The Journal of Rheumatology. 2003 February; 30(2): 288-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563682&dopt=Abstract •
Single-photon-emission computed tomography analysis of cerebral blood flow in the evaluation of central nervous system involvement in patients with systemic lupus erythematosus. Author(s): Rubbert A, Marienhagen J, Pirner K, Manger B, Grebmeier J, Engelhardt A, Wolf F, Kalden JR. Source: Arthritis and Rheumatism. 1993 September; 36(9): 1253-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8216419&dopt=Abstract
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Specific psychosocial and behavioral outcomes from the systemic lupus erythematosus self-help course. Author(s): Braden CJ, McGlone K, Pennington F. Source: Health Educ Q. 1993 Spring; 20(1): 29-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8444623&dopt=Abstract
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Stabilization of the classical pathway C3 convertase C42, by a factor F-42, isolated from serum of patients with systemic lupus erythematosus. Author(s): Daha MR, Hazevoet HM, Vanes LA, Cats A. Source: Immunology. 1980 July; 40(3): 417-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6903557&dopt=Abstract
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Suppression of experimental systemic lupus erythematosus (SLE) with specific antiidiotypic antibody-saporin conjugate. Author(s): Blank M, Manosroi J, Tomer Y, Manosroi A, Kopolovic J, Charcon-Polak S, Shoenfeld Y. Source: Clinical and Experimental Immunology. 1994 December; 98(3): 434-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7994908&dopt=Abstract
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Sustained normalization of cerebral blood-flow after iloprost therapy in a patient with neuropsychiatric systemic lupus erythematosus. Author(s): Mathieu A, Sanna G, Mameli A, Pinna C, Vacca A, Cauli A, Passiu G, Piga M. Source: Lupus. 2002; 11(1): 52-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898921&dopt=Abstract
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Systemic lupus erythematosus six years following chemotherapy for malignant lymphoma. Author(s): Berliner S, Sidi Y, Mor C, Galili N, Weinberger A, Pinkhas J. Source: Scandinavian Journal of Rheumatology. 1985; 14(3): 276-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4048875&dopt=Abstract
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The bite of a wolf: systemic lupus erythematosus. Author(s): Bertino LS, Lu LC. Source: Rehabilitation Nursing : the Official Journal of the Association of Rehabilitation Nurses. 1993 May-June; 18(3): 173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8502843&dopt=Abstract
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The effects of Chinese herbs on improving survival and inhibiting anti-ds DNA antibody production in lupus mice. Author(s): Chen JR, Yen JH, Lin CC, Tsai WJ, Liu WJ, Tsai JJ, Lin SF, Liu HW. Source: The American Journal of Chinese Medicine. 1993; 21(3-4): 257-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8135170&dopt=Abstract
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The nature of lupus erythematosus in mice. Author(s): Gabrielsen AE. Source: Cutis; Cutaneous Medicine for the Practitioner. 1979 April; 23(4): 401-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=428247&dopt=Abstract
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The need for lupus support groups. Author(s): Marx J. Source: Health Values. 1985 March-April; 9(2): 35-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10270140&dopt=Abstract
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The neuropsychiatric manifestations of systemic lupus erythematosus: an overview. Author(s): Adelman DC, Saltiel E, Klinenberg JR. Source: Seminars in Arthritis and Rheumatism. 1986 February; 15(3): 185-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3515561&dopt=Abstract
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The occurrence of psychiatric illness in systemic lupus erythematosus. Author(s): Guze SB. Source: The American Journal of Psychiatry. 1967 June; 123(12): 1562-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6025190&dopt=Abstract
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The prognosis of biopsy-proven lupus nephritis in chinese patients: long term follow-up of 86 cases. Author(s): Shen K, Yu Y, Tang Z, Liu Z, Li L. Source: Chin Med J (Engl). 1997 July; 110(7): 502-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9594205&dopt=Abstract
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The protective effect of dietary fish oil on murine lupus. Author(s): Robinson DR, Prickett JD, Polisson R, Steinberg AD, Levine L.
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Source: Prostaglandins. 1985 July; 30(1): 51-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4048478&dopt=Abstract •
The role of diet in animal models of systemic lupus erythematosus: possible implications for human lupus. Author(s): Corman LC. Source: Seminars in Arthritis and Rheumatism. 1985 August; 15(1): 61-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3898377&dopt=Abstract
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The use of alternative medical therapies in patients with systemic lupus erythematosus. Trination Study Group. Author(s): Moore AD, Petri MA, Manzi S, Isenberg DA, Gordon C, Senecal JL, St Pierre Y, Joseph L, Penrod J, Fortin PR, Sutcliffe N, Goulet JR, Choquette D, Grodzicky T, Esdaile JM, Clarke AE. Source: Arthritis and Rheumatism. 2000 June; 43(6): 1410-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10857802&dopt=Abstract
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Therapy of systemic lupus erythematosus: a look into the future. Author(s): Smolen JS. Source: Arthritis Research. 2002; 4 Suppl 3: S25-30. Epub 2002 May 09. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110120&dopt=Abstract
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Thermal feedback in Raynaud's phenomenon secondary to systemic lupus erythematosus: long-term remission of target symptoms. Author(s): Sappington JT, Fiorito EM. Source: Biofeedback Self Regul. 1985 December; 10(4): 335-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3915700&dopt=Abstract
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Thymosin-induced reduction of “null cells” in peripheral-blood lymphocytes of patients with systemic lupus erythematosus. Author(s): Scheinberg MA, Cathcart ES, Goldstein AL. Source: Lancet. 1975 February 22; 1(7904): 424-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=48612&dopt=Abstract
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Treatment of chronic discoid lupus erythematosus with large doses of vitamin B12. Author(s): MARCUS MD, CONRAD AH Jr, WEISS RS. Source: The Journal of Investigative Dermatology. 1953 August; 21(2): 75-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13084968&dopt=Abstract
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Treatment of systemic lupus erythematosus by acupuncture. A preliminary report of 25 cases. Author(s): Feng SF, Fang L, Bao GQ, Wei W, Yang GL, Xiang ZS, Shi SY.
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Source: Chin Med J (Engl). 1985 March; 98(3): 171-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3924508&dopt=Abstract •
Understanding lupus. Author(s): Barwick AR. Source: Nursing Standard : Official Newspaper of the Royal College of Nursing. 2000 August 2-8; 14(46): 47-51; Quiz 53-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11974135&dopt=Abstract
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Urtica dioica agglutinin, a V beta 8.3-specific superantigen, prevents the development of the systemic lupus erythematosus-like pathology of MRL lpr/lpr mice. Author(s): Musette P, Galelli A, Chabre H, Callard P, Peumans W, Truffa-Bachi P, Kourilsky P, Gachelin G. Source: European Journal of Immunology. 1996 August; 26(8): 1707-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8765010&dopt=Abstract
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Use of alternative medicine in a consecutive sample of patients with systemic lupus erythematosus. Author(s): Ramos-Remus C, Gamez-Nava JI, Gonzalez-Lopez L, Suarez-Almazor ME. Source: The Journal of Rheumatology. 1997 December; 24(12): 2490-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415671&dopt=Abstract
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Visual scotomata resulting from lupus anticoagulant in a patient with lymphoma in remission. Author(s): Gruber ML, Hochberg FH. Source: Journal of Neuro-Oncology. 1991 December; 11(3): 255-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1726657&dopt=Abstract
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Vitamin D levels in women with systemic lupus erythematosus and fibromyalgia. Author(s): Huisman AM, White KP, Algra A, Harth M, Vieth R, Jacobs JW, Bijlsma JW, Bell DA. Source: The Journal of Rheumatology. 2001 November; 28(11): 2535-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708429&dopt=Abstract
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Why lupus patients use alternative medicine. Author(s): Leong KP, Pong LY, Chan SP. Source: Lupus. 2003; 12(9): 659-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514127&dopt=Abstract
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Witchcraft and lupus erythematosus. Author(s): Kirkpatrick RA.
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Source: Jama : the Journal of the American Medical Association. 1981 May 15; 245(19): 1937. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7230386&dopt=Abstract •
Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupuslike syndrome. Author(s): Sandler B, Aronson P. Source: Urology. 1993 April; 41(4): 343-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8470320&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to lupus; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Angioedema Source: Integrative Medicine Communications; www.drkoop.com Cholesterol, High Source: Integrative Medicine Communications; www.drkoop.com
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Colds and Flus Source: Prima Communications, Inc.www.personalhealthzone.com Depression Source: Integrative Medicine Communications; www.drkoop.com Erythema Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Indigestion, Heartburn, and Low Stomach Acidity Source: Healthnotes, Inc. www.healthnotes.com Lupus Source: Integrative Medicine Communications; www.drkoop.com Pancreatic Insufficiency Source: Healthnotes, Inc. www.healthnotes.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Photosensitivity Source: Healthnotes, Inc. www.healthnotes.com Raynaud's Phenomenon Source: Integrative Medicine Communications; www.drkoop.com Rheumatoid Arthritis Source: Prima Communications, Inc.www.personalhealthzone.com Scleroderma Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Healthnotes, Inc. www.healthnotes.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com
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Alternative Therapy Chelation Therapy Source: Healthnotes, Inc. www.healthnotes.com Myotherapy Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,931,00.html
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Herbs and Supplements Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org ALA Source: Integrative Medicine Communications; www.drkoop.com Alfalfa Alternative names: Medicago sativa Source: Healthnotes, Inc. www.healthnotes.com Alpha-Linolenic Acid (ALA) Source: Integrative Medicine Communications; www.drkoop.com Androstenedione Source: Healthnotes, Inc. www.healthnotes.com Astragalus Alternative names: Astragalus membranaceus Source: Healthnotes, Inc. www.healthnotes.com Astragalus mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Beta-carotene Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10103,00.html Bromelain Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,760,00.html Corticosteroids Source: Prima Communications, Inc.www.personalhealthzone.com Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc. www.healthnotes.com
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Dehydroepiandrosterone (DHEA) Source: Integrative Medicine Communications; www.drkoop.com DHEA Source: Integrative Medicine Communications; www.drkoop.com DHEA Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10022,00.html DHEA (Dehydroepiandrosterone) Source: Prima Communications, Inc.www.personalhealthzone.com Docosahexaenoic Acid Source: Healthnotes, Inc. www.healthnotes.com Echinacea Alternative names: Echinacea purpurea, Echinacea angustifolia, Echinacea pallida Source: Healthnotes, Inc. www.healthnotes.com Echinacea Source: Prima Communications, Inc.www.personalhealthzone.com Echinacea Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,775,00.html EDTA Source: Integrative Medicine Communications; www.drkoop.com Ethylenediaminetetraacetic Acid (EDTA) Source: Integrative Medicine Communications; www.drkoop.com Flaxseed Alternative names: Linum usitatissimum, Linseed Source: Integrative Medicine Communications; www.drkoop.com Grape seed extract Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,793,00.html Hydroxychloroquine Source: Healthnotes, Inc. www.healthnotes.com Linseed Source: Integrative Medicine Communications; www.drkoop.com
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Linum usitatissimum Source: Integrative Medicine Communications; www.drkoop.com Melatonin Source: Healthnotes, Inc. www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com MSM Source: WholeHealthMD.com, LLC. www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,807,00.html Oral Corticosteroids Source: Healthnotes, Inc. www.healthnotes.com PABA Source: Healthnotes, Inc. www.healthnotes.com Pau D’arco Alternative names: Tabebuia avellanedae, Tabebuia impestiginosa Source: Healthnotes, Inc. www.healthnotes.com Pregnenolone Source: Healthnotes, Inc. www.healthnotes.com Uncaria CatClaw Alternative names: Cat's Claw, Uno de Gato; Uncaria tomentosa (Willd.) D.C. Source: Alternative Medicine Foundation, Inc. www.amfoundation.org
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON LUPUS Overview In this chapter, we will give you a bibliography on recent dissertations relating to lupus. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “lupus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lupus, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Lupus ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to lupus. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
A Pilot Study of a Translated, Culturally Sensitive Systemic Lupus Erythematosus Self-help Course for Latino Lupus Patients (spanish Text) by Robbins, Laura, Dsn from City University of New York, 1994, 380 pages http://wwwlib.umi.com/dissertations/fullcit/9432374
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A Study of Lifelong Transitions, Experiential Learnings, and Coping Responses of Six Female Systemic Lupus Erythematosus Patients between the Ages of 20 and 51 Years (chronic Illness) by Scott, James Joseph, Phd from Michigan State University, 1991, 213 pages http://wwwlib.umi.com/dissertations/fullcit/9216359
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Aspects of the Early Social Development of Timber Wolves (canis Lupus) by Mcleod, Peter John; Phd from Dalhousie University (canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL40164
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Assessing the Potential, Actual, and Perceived Risk That Gray Wolves, Canis Lupus, Pose to Livestock in Northwestern Minnesota by Chavez, Andreas Shintaro; Ms from Utah State University, 2002, 118 pages http://wwwlib.umi.com/dissertations/fullcit/1409337
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Autoantibodies and the Type I Interferon System in the Etiopathogenesis of Systemic Lupus Erythematosus by Blomberg, Stina; Phd from Uppsala Universitet (sweden), 2003, 50 pages http://wwwlib.umi.com/dissertations/fullcit/f118833
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Behavioral Ecology of Sympatric Wolves, Canis Lupus, and Coyotes, C. Latrans, in Riding Mountain National Park, Manitoba by Paquet, Paul C; Phd from University of Alberta (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL52928
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Characterization of the Reactivities of Sle and Normal-derived Human Hybridoma Lupus Anticoagulant, Anti-phospholipid and Anti-ddna Autoantibodies with Platelets and Endothelial Cells by Meng, Qiang-hua; Phd from Mcgill University (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL57155
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Childhood Neuropsychiatric Systemic Lupus Erythematosus: an Analysis of Neuropsychological Performance by Romain, Jonathan Edward; Phd from Alliant International University, Fresno, 2002, 96 pages http://wwwlib.umi.com/dissertations/fullcit/3062686
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Conjugated Linoleic Acid (cla) Prolongs the Survival and Reduces Cachexia of the Autoimmune Nzb/w F1 Mouse: Role of Cytokine Regulation by Cla in Body Weight Wasting and Murine Systemic Lupus Erythematosus by Yang, Ming-der; Phd from The University of Wisconsin - Madison, 2002, 183 pages http://wwwlib.umi.com/dissertations/fullcit/3049400
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Cryopreservation of Mexican and Gray Wolf Spermatazoa and Reproductive Characteristics of the Mexican Wolf Population (canis Lupus) by Musson, Annabel Jane; Msc from University of Guelph (canada), 2002, 110 pages http://wwwlib.umi.com/dissertations/fullcit/MQ71205
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Exploring the Lived Experiences of Rural Women with Systemic Lupus Erythematosus by Rennegarbe, Richelle Annette; Phd from Southern Illinois University at Carbondale, 2002, 210 pages http://wwwlib.umi.com/dissertations/fullcit/3065381
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Form and Strategy of Combative Interactions between Wolf Pups (canis Lupus) by Havkin, Zvika; Phd from Dalhousie University (canada), 1981 http://wwwlib.umi.com/dissertations/fullcit/NK53693
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Genetic Mapping of Susceptibility Genes for Systemic Lupus Erythematosus by Johanneson, Bo; Phd from Uppsala Universitet (sweden), 2002, 44 pages http://wwwlib.umi.com/dissertations/fullcit/f680209
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Genetic Studies of Systemic Lupus Erythematosus: a Fine Mapping and Candidate Gene Approach by Magnusson, Veronica; Phd from Uppsala Universitet (sweden), 2002, 54 pages http://wwwlib.umi.com/dissertations/fullcit/f680225
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Health Status and Coping Behavior in Lupus Patients by Overman, Lynn B. Phd from The University of Alabama at Birmingham, 2002, 91 pages http://wwwlib.umi.com/dissertations/fullcit/3078545
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Humoral Autoimmunity As a Link to the Origins and Development of Systemic Lupus Erythematosus by Mcclain, Micah Thomas; Phd from The University of Oklahoma Health Sciences Center, 2002, 166 pages http://wwwlib.umi.com/dissertations/fullcit/3053940
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Localization and Finemapping of Human Systemic Lupus Erythematosus Susceptibility Loci at Chromosome 6p21.3 (the Human Leukocyte Antigen Region) and Chromosome 1q41 by Graham, Robert Royal; Phd from University of Minnesota, 2002, 132 pages http://wwwlib.umi.com/dissertations/fullcit/3069193
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Lupus in Fabula : the Wolf in Medieval German Fables by Wooller, Susan; Phd from Mcgill University (canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK29484
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Lupus in Fabula: the Wolf in Medieval German Fables. by Wooller, Susan Jacqueline, Phd from Mcgill University (canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/f3452422
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Lupus of Ferrieres and the Classics by Gariepy, Robert Joseph, Jr, Phd from University of Washington, 1965, 156 pages http://wwwlib.umi.com/dissertations/fullcit/6605836
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Lupus of Ferrieres: Scholar, Humanist, Monk. by Nusbaum, Daniel Charles, Phd from Fordham University, 1977, 200 pages http://wwwlib.umi.com/dissertations/fullcit/7714903
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Lupus: Managing a Complex Chronic Disability by Labrie, Vida Yvonne, Phd from University of California, San Francisco, 1987, 185 pages http://wwwlib.umi.com/dissertations/fullcit/8708450
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Mechanisms for Interferon-alpha Induction in Systemic Lupus Erythematosus by Bave, Ullvi; Phd from Uppsala Universitet (sweden), 2003, 70 pages http://wwwlib.umi.com/dissertations/fullcit/f113937
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Patient-physician Discordance in Systemic Lupus Erythematosus and Its Impact on Medication Adherence and Alternative Medicine Use by Yen, Jim C. Phd from Mcgill University (canada), 2002, 315 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78803
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Prognosis in Systemic Lupus Erythematosus the Contribution of Renal Biopsy and Variables That Change Through Time by Mclaughlin, John Ross; Phd from University of Toronto (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL54638
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Relationship Adjustment, Partner Support, and Psychosocial Outcomes for Women with Systemic Lupus Erythematosus by Lewis, Traci Lyn; Phd from The Ohio State University, 2002, 91 pages http://wwwlib.umi.com/dissertations/fullcit/3081939
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Relationship of Locus-of-control, Disease Status and Coping Perceptions of Systemic Lupus Erythematosus Patients (patient Education, Lupus Erythematosus) by Reichenberger, Patricia Viola, Phd from University of Kansas, 1992, 91 pages http://wwwlib.umi.com/dissertations/fullcit/9313158
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Social Networks and Self-reported Symptomatology of Women with Systemic Lupus Erythematosus by Montes, Nivia; Ms from The University of Texas Graduate Sch. of Biomedical Sci. at Galveston, 2002, 85 pages http://wwwlib.umi.com/dissertations/fullcit/1407983
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Social Support and Psychological Distress in Women with Systemic Lupus Erythematosus by Keller, Shirley M., Phd from Case Western Reserve University, 1999, 167 pages http://wwwlib.umi.com/dissertations/fullcit/9927315
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Study of a Peptide-induced Lupus Model by Wang, Chuansheng; Phd from Yeshiva University, 2003, 234 pages http://wwwlib.umi.com/dissertations/fullcit/3080982
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The Contribution of Social Role Adjustment, Employment Status and Health Locusof-control to Psychological Distress in Women with Systemic Lupus Erythematosus by Persse, Linda Jo, Phd from Case Western Reserve University, 1993, 142 pages http://wwwlib.umi.com/dissertations/fullcit/9406289
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The Ecology of Gray Wolf (canis Lupus) Habitat Use, Survival, and Persistence in the Central Rocky Mountains, Canada by Callaghan, Carolyn Joann; Phd from University of Guelph (canada), 2002, 211 pages http://wwwlib.umi.com/dissertations/fullcit/NQ67227
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The Effects of Lupus on Flannery O'connor and Some of Her Works (systemic Lupus Erythematosus) by Davis, Elizabeth Deidre, Edd from West Virginia University, 1995, 305 pages http://wwwlib.umi.com/dissertations/fullcit/9543836
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The Patient Communication Model: Application to Systemic Lupus Erythematosus Patients by Austin, Janet S., Phd from University of Alabama at Birmingham, 1995, 159 pages http://wwwlib.umi.com/dissertations/fullcit/9615413
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The Role of the Alternative Pathway of Complement in Lupus Nephritis by Elliott, Margaret Kathryn; Phd from Medical University of South Carolina, 2002, 151 pages http://wwwlib.umi.com/dissertations/fullcit/3070110
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The Socioendocrinology of Aggression-mediated Stress in Timber Wolves (canis Lupus) by Gadbois, Simon; Phd from Dalhousie University (canada), 2002, 283 pages http://wwwlib.umi.com/dissertations/fullcit/NQ75700
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Utility of Pender's Model in Describing Health-promoting Behaviors in Thai Women with Systemic Lupus Erythematosus by Sriyuktasuth, Aurawamon; Dsn from The University of Alabama at Birmingham, 2002, 122 pages http://wwwlib.umi.com/dissertations/fullcit/3066344
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND LUPUS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning lupus.
Recent Trials on Lupus The following is a list of recent trials dedicated to lupus.8 Further information on a trial is available at the Web site indicated. •
Anti-CD20 in Systemic Lupus Erythematosus Condition(s): Lupus Erythematosus, Systemic Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to determine the safety and effectiveness of rituximab (anti-CD20) in treating systemic lupus erythematosus (SLE). White blood cells in the body called B cells give off substances that are active in promoting SLE disease. Researchers have found that anti-CD20 can block production of these substances in another disease. This study explores whether anti-CD20 will also be safe in people with SLE and whether it may be effective in treating SLE. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00036491
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Dexamethasone in Lupus Congenital Heart Block of Newborns Condition(s): Congenital heart block; Neonatal lupus; Atrioventricular nodal dysfunction; Myocardial injury Study Status: This study is currently recruiting patients.
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These are listed at www.ClinicalTrials.gov.
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Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study has two parts. The goal of the first part is to find out the usefulness of giving medications known as fluorinated steroids to pregnant women whose unborn children have a heart condition called congenital heart block (CHB). CHB occurs in some babies with neonatal lupus, a form of lupus that affects newborns but usually disappears by the time the infant is 3-6 months old. We will look at whether giving a steroid drug, such as dexamethasone, to pregnant women improves the heart function and general health of newborns who have autoantibody-associated CHB. This form of CHB is linked to the presence of certain blood proteins (antibodies) in the mother. Women enrolled must have antibodies to SSA/Ro and/or SSB/La and must be carrying a fetus with first, second, or third degree CHB diagnosed during gestation. It will be the decision of the physician and the mother as to whether a medication such as dexamethasone will be administered. The second part of the study will examine pregnant women who are at high risk for having babies with CHB to identify the earliest signs of heart problems in the unborn child that can be detected using ultrasound testing. We will follow 100 mothers considered at high risk for having a child with CHB by doing weekly echocardiograms (a noninvasive method that uses ultrasound to produce images of the heart) of the fetus from the 16th week of pregnancy. From week 28 to 34, echocardiograms will be performed every other week. Phase(s): Phase II Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007358 •
Genetic Studies of Lupus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: The Lupus Genetic Linkage Study and Lupus Multiplex Registry & Repository are working to find the genes that cause systemic lupus erythematosus (SLE, or lupus). The study is enrolling families of all ethnic backgrounds from the United States, Canada, Puerto Rico, and the Virgin Islands that have two or more living members diagnosed with SLE. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071175
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Immune System Related Kidney Disease Condition(s): Glomerulonephritis; Lupus Nephritis; Membranous Glomerulonephritis; Nephritis; Nephrotic Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Purpose - Excerpt: Kidney diseases related to the immune system include, nephrotic syndrome, glomerulonephritis, membranous nephropathy, lupus nephritis, and nephritis associated with connective tissue disorders. This study will allow researchers to admit and follow patients suffering from autoimmune diseases of the kidney. It will attempt to provide information about the causes and specific abnormalities associated with autoimmune kidney disease. Patients with kidney disease as a result of their immune system, and patients with diseases of the immune system who may later develop kidney disease, will be potential subjects for this study. Patients will undergo a history and physical examination, and standard laboratory test to more closely understand the causes, signs, symptoms, and responses to medication of these diseases. Based on these evaluations the patients may qualify as candidates for other experimental studies. At any time these patients may be asked to submit blood or urine samples for further research. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001979 •
Monoclonal Antibody Treatment for Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will examine the safety and effects of the monoclonal antibody MRA in patients with systemic lupus erythematosus (SLE). Antibodies normally fight invading organisms. In autoimmune diseases, such as lupus, however, antibodies attack the body's own tissues. MRA is an antibody manufactured in the laboratory that blocks the action of interleukin-6 (IL-6), a substance that increases antibody production and is involved in inflammation that may cause organ damage in SLE. Patients 18 years of age and older with moderately active systemic lupus erythematosus may be eligible for this 6-month study. Candidates will be screened with blood and urine tests, chest X-ray, electrocardiogram (EKG), and screening tests for certain cancers. Participants will receive a total of up to seven infusions of MRA given every 2 weeks in the clinic. The MRA is infused over a period of about 1 hour through a catheter (thin plastic tube) inserted into an arm vein. Patients will be observed for 1 to 2 hours after each infusion for drug side effects. For the first and last infusions, patients will return to the clinic for blood tests 24 to 48 hours after the infusion. Additional tests may be done if medically indicated. Three different doses of MRA will be used in three groups of patients. The first group (4 patients) will receive the lowest dose. If this dose is well tolerated, a second group (6 patients) will receive a higher dose. If this dose is also well tolerated, a third group (6 patients) will receive the highest study dose. Patients will be evaluated at various intervals for up to 3 months after the last dose of MRA. The follow-up visits will include a review of the patient's medical history, a physical examination, blood and urine tests, and an EKG. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046774
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Phase I Study of Immune Ablation and CD34+ Peripheral Blood Stem Cell Support in Patients With Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): Northwestern Memorial Hospital Purpose - Excerpt: Objectives: I. Determine the safety of immune ablation with highdose cyclophosphamide and anti-thymocyte globulin followed by peripheral blood stem cell support in patients with systemic lupus erythematosus. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00017641
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Phase II Study of Ultraviolet A-1 Light Therapy for Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Louisiana State University Purpose - Excerpt: Objectives: I. Evaluate the mechanisms of ultraviolet A-1 light therapy in patients with systemic lupus erythematosus and normal controls. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004375
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Pilot Study of Cyclophosphamide in Patients With Life-Threatening Systemic Lupus Erythematosus or Antiphospholipid Antibody Syndrome Condition(s): Systemic Lupus Erythematosus; Antiphospholipid Antibody Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): Johns Hopkins Oncology Center Purpose - Excerpt: Objectives: I. Determine the induction of durable remission in patients with life-threatening systemic lupus erythematosus or antiphospholipid antibody syndrome treated with cyclophosphamide. II. Determine the toxicity of this drug in these patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010400
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Pilot Study of Total Body Irradiation in Combination With Cyclophosphamide, Antithymocyte Globulin, and Autologous CD34-Selected Peripheral Blood Stem Cell Transplantation in Children With Refractory Autoimmune Disorders Condition(s): Systemic Sclerosis; Systemic Lupus Erythematosus; Dermatomyositis; Juvenile Rheumatoid Arthritis; Autoimmune Diseases
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Study Status: This study is currently recruiting patients. Sponsor(s): Fred Hutchinson Cancer Research Center Purpose - Excerpt: Objectives: I. Determine the safety and long term complications of total body irradiation in combination with cyclophosphamide, anti-thymocyte globulin, and autologous CD34-selected peripheral blood stem cell (PBSC) transplantation in children with refractory autoimmune disorders. II. Determine the efficacy of this treatment regimen in these patients. III. Determine the reconstitution of immunity after autologous CD34-selected PBSC transplantation in these patients. IV. Determine engraftment of autologous CD34-selected PBSC in these patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010335 •
Prevention of Atherosclerosis and Heart Disease in Patients with Systemic Lupus Erythematosis (SLE) Condition(s): Systemic Lupus Erythematosus; Lupus Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: The purpose of this study is to find the best way to prevent heart disease and stroke in people with lupus (systemic lupus erythematosis, or SLE). The study will evaluate the effectiveness of medication and a phone-based education program in controlling four risk factors for heart disease: smoking, obesity, high blood pressure, and inactivity. The study will also test the safety of commonly used heart medications in people with lupus. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054938
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Randomized Study of Oral Contraceptives or Hormone Replacement Therapy in Women With Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); UAB Comprehensive Cancer Center Purpose - Excerpt: Objectives: I. Determine the effect of oral contraceptives containing low-dose synthetic estrogens and progestins on disease activity in premenopausal women with inactive, stable, or moderate systemic lupus erythematosus (SLE). II. Determine the effect of hormone replacement therapy with conjugated estrogens and progestins on disease activity in postmenopausal women with inactive, stable, or moderate SLE. Study Type: Interventional Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00006133 •
Role of altered CD40-Ligand gene transcription in systemic lupus erythematosus Condition(s): Lupus Erythematosus, Systemic Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); Arthritis Foundation Purpose - Excerpt: Systemic lupus erythematosus is an often devastating autoimmune disease which affects 1 in 2,000 women in the United States. Recently, several research laboratories have reported that a protein, named CD40-ligand (CD154), is overexpressed by a subset of white blood cells, called lymphocytes, in patients with lupus. Expression of CD154 appears critical to the generation of antibodies that cause disease in lupus. Blocking CD154 interactions in the immune system has been shown to decrease disease activity in animal models of lupus. We propose to study the regulation of CD154 in patients with lupus in hopes of inhibiting its abnormal and deleterious expression. Study Type: Observational Contact(s): Randy Q Cron, MD, Ph.D. 215-590-1844 Web Site: http://clinicaltrials.gov/ct/show/NCT00008749
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Role of Antibodies in Cognitive Dysfunction in Patients with Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will examine the possible relationship between certain antibodies found in patients with systemic lupus erythematosus (SLE) and cognitive (thought processing) impairment in these patients. Antibodies are proteins produced by cells of the immune system to fight foreign invaders such as bacteria and viruses. In autoimmune diseases like SLE, however, the immune system produces antibodies against the body's own healthy tissues. Antibodies targeting the brain may cause cognitive dysfunction. Many patients with SLE have mild to severe cognitive impairment involving, for example, short- or long-term memory, thought processing and relating objects in time and space. Patients 18 years of age and older with SLE may be eligible for this study. Participants will undergo the following tests and procedures: Medical history and physical examination, including blood and urine tests - Psychiatric interview and questionnaire to assess depression - Neuropsychological tests - answering questions given by an examiner or filling out a test form or questionnaire - Tests of cognitive function - answering questions given by an automated computer program or performing tasks using a computer mouse - Magnetic resonance imaging (MRI) of the brain - a test that uses strong magnetic fields and radio waves to generate images of the brain. The patient lies still on a stretcher inside a cylinder containing a magnetic field. The patient's head is stabilized with a plastic strap and foam pads. During the imaging, a substance called gadolinium-DTPA is injected into an arm vein through a catheter (thin plastic tube). This substance is used to enhance the images. Patients may also be asked to undergo an optional procedure called a lumbar puncture (spinal tap) to examine the relationship between cognitive impairment and the amount of antibodies in the cerebrospinal fluid (CSF)- fluid that circulates around the brain and spinal cord. For
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this procedure a small area of skin on the lower back is numbed with a local anesthetic. A needle is then inserted in the space between the bones in the lower back, and about 2 tablespoons of CSF is withdrawn through the needle. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042523 •
Sirolimus Therapy for Idiopathic and Lupus Membranous Nephropathy Condition(s): Membranous Glomerulonephritis Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: This study will evaluate the safety and effectiveness of a new immunosuppressive drug, sirolimus, in reducing the amount of protein in the urine in patients with membranous nephropathy. This condition involves damage to the walls of tiny blood vessel filters in the kidneys called glomeruli, which allows blood proteins to leak into the urine. Patients have low blood protein levels and high blood cholesterol. Some patients may have leg swelling, impaired kidney function, blood vessel and heart disease, and a risk of emboli (blood clots that travel to the lungs). Drugs currently used to treat membranous nephropathy vary in their effectiveness among patients and can cause severe side effects. The Food and Drug Administration has approved sirolimus for suppressing the immune system of patients who have had a kidney transplant to reduce the risk of organ rejection. The drug does not have certain side effects that have caused problems for patients treated with other immunosuppressants, such as: prednisone (weight gain, round face, diabetes, weak and fractured bones, and cataracts); cyclophosphamide (fertility problems, bladder injury and bladder cancer, and other cancers); chlorambucil (fertility problems, seizures, acute leukemia, and other cancers); and cyclosporine (kidney toxicity, increased facial hair, and seizures). Patients 13 years of age or older with idiopathic membranous nephropathy or lupus membranous nephropathy may be eligible for this study. Candidates must have completed at least one month of treatment with a stable dose of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). They will be screened with a medical history, physical examination, blood tests, skin test for exposure to tuberculosis, and an examination for infection, cancers, and other conditions that can cause membranous nephropathy. Participants will take sirolimus once a day for 1 year, except for the first day of treatment, when they will take three doses to quickly bring their blood levels of the drug up to a therapeutic level. They will undergo evaluations at the NIH in Bethesda, Maryland, at baseline (before starting treatment) and again at 1- to 4-month intervals during the study. In addition, they will have blood tests every week for the first month and every 2 weeks for the second month; then blood and urine tests once a month for the next 10 months of treatment and then every 4 months for a 12-month period after treatment stops. These tests will evaluate drug side effects and the response to therapy, and will determine if the therapeutic benefits persist long-term when treatment stops. Patients will also be asked to have optional kidney function tests during the baseline evaluation and at the end of the follow-up period to measure kidney filtration and blood flow rates. Those who participate will be given fluids and other substances by vein to accurately measure kidney function. They will then have blood and urine samples collected about four times over a 1-hour period after drinking fluids to increase urine output. Patients who experience a substantial increase in proteinuria or
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substantial decrease in kidney function during the course of treatment will stop taking sirolimus and be taken off the study. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050713 •
Six month clinical research study for patients with moderate or severe dry eye syndrome Condition(s): Keratoconjunctivitis Sicca; Sjogren's Syndrome; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid; Scleroderma, Systemic Study Status: This study is currently recruiting patients. Sponsor(s): Allergan Purpose - Excerpt: A six-month clinical research trial to evaluate the effectiveness of an investigational medication for the treatment of dry eye syndrome in patients that have been diagnosed with moderate to severe dry eye syndrome, an autoimmune disorder AND/OR females 65 years of age or older. Phase(s): Phase III Study Type: Interventional Contact(s): Rheumatology Research International 1-888-297-4247
[email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00025818
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Study of Families with Twins or Siblings Discordant for Rheumatic Disorders Condition(s): Rheumatic Diseases; Rheumatoid Arthritis; Erythematosus; Scleroderma; Dermatomyositis; Myositis
Systemic
Lupus
Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Environmental Health Sciences (NIEHS) Purpose - Excerpt: This study will examine families in which one sibling of a sibling pair, or twin pair, has developed a systemic rheumatic disease and one has not, to see if and how the two differ in the following: - Blood cell metabolism; - Types of cells in the blood; - Environmental exposures or genetic factors that might explain why one developed disease and the other did not. Families in which one sibling has developed a systemic rheumatic disease, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, dermatomyositis, or myositis, and the other has not, are eligible for this study. The siblings may or may not be twins, but must be of the same gender and be within a 3-year age difference. Biological parents, or, in some cases, children, will also be included in the study. Normal, healthy volunteers will serve as control subjects. Participants will undergo some or all of the following tests and procedures: - Medical history and physical examination. Participants will also be asked permission to obtain medical records for review. - Questionnaires about environmental exposures at work, at home, and elsewhere. Probands (participants with rheumatic disease) and their healthy siblings will also answer questions about infections, vaccinations, medications or dietary supplements, sun exposure, and stressful events during the year before disease diagnosis in the affected sibling. - Blood and urine collection for the following tests: Routine blood chemistries and other studies to rule out certain diseases or medical
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problems; - Evidence of past toxic exposures and certain infections; - Presence of cells from the mother in the child's blood and vice versa. (Recent studies suggest that during pregnancy or delivery, cells from the mother and baby may be exchanged and circulate in the body for many years, possibly causing problems); - In twin or sibling pairs, presence of certain genes that may be more common in patients with systematic rheumatic diseases as compared with their unaffected siblings and normal volunteers; In identical twins, comparison of their blood cell metabolism to see if and how the metabolism differs in people with rheumatic disease. Participants may be asked for permission to have some of their blood and urine samples stored and to obtain previously collected blood or tissue biopsy specimens that are no longer needed for clinical care, for research purposes. They may also be asked to give additional blood or urine samples. Participants will be followed every year for 5 years (either in person or by questionnaire) to evaluate any changes in their condition. The final 5-year evaluation will repeat some of the questionnaires and procedures described above. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055055 •
Study of GL701 in Men with Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): Genelabs Technologies Purpose - Excerpt: Lupus flares and other symptoms associated with systemic lupus erythematosus (SLE) may be caused by a deficiency of dehydroepiandrosterone (DHEA). GL701 is an investigational new drug meant to enhance DHEA levels. This study is designed to evaluate both the safety and efficacy of GL701 in male lupus patients. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037128
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Study of Systemic Lupus Erythematosus Condition(s): Lupus Nephritis; Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This protocol will evaluate patients with systemic lupus erythematosus (SLE) and their relatives to learn more about how the disease develops and changes over time. It will also study genetic factors that make a person susceptible to SLE. Patients 10 years of age and older with known or suspected SLE and their relatives may be eligible for this study. Patients will be evaluated with a medical history and physical examination, blood and urine tests. Other procedures may include: 1. Electrocardiogram 2. 24-hour urine collection 3. Imaging studies, such as chest and joint X-rays, magnetic resonance imaging (MRI) scans, bone scans, and bone densitometry. 4. Questionnaire about the degree of disease activity, and survey of risk factors for disease
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complications. 5. Apheresis-Collection of plasma (fluid portion of blood) or blood cells for analysis. Whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The required component (plasma or cells) is removed and the rest of the blood is returned to the body through the same needle or through a second needle in the other arm. 6. Skin biopsyRemoval of a small skin sample for microscopic analysis. An area of skin is numbed with an anesthetic and a small circular portion (about 1/4 inch in diameter) is removed, using a sharp cookie cutter-type instrument. 7. Kidney, bone marrow or other organ biopsy-Removal of a small sample of organ tissue. These biopsies are done only if they can provide information useful in better understanding the disease or making treatment decisions. 8. Genetic studies-Collection of a blood sample for gene testing. Patients will be followed at least once a year with a brief history and physical examination and routine blood and urine tests. Some patients may be seen more often. Treatment recommendations will be offered to patients' physicians, and patients who are eligible for other research treatment studies will be invited to enroll. Participating relatives of patients will fill out a brief medical history questionnaire and provide a DNA sample (either a blood sample or tissue swab from the inside of the cheek) for genetic testing. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001372 •
Study of the Predictors of the Course and Early Outcome of Patients With Systemic Lupus Erythematosus: Nature Versus Nurture Condition(s): Systemic Lupus Erythematosus Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Research Resources (NCRR); UAB Comprehensive Cancer Center Purpose - Excerpt: Objectives: I. Continue yearly ascertainment visits of all patients of the established Lupus in Minority Populations: Nature vs Nurture (LUMINA) study cohort. II. Recruit into the LUMINA cohort newly diagnosed patients with systemic lupus erythematosus (SLE). III. Determine the impact of additional major histocompatibility complex (MHC) and non-MHC genetic factors not previously examined, specifically tumor necrosis factor, mannose binding protein, interleukin-1 receptor antagonist, and bcl-2, on the course and outcome of SLE. IV. Refine the assessment of those clinical and behavioral-cultural factors found to be important predictors of disease activity, damage, and functioning, thus far in these patients. V. Determine the relationships among disease activity, disease damage, and physical and mental functioning in these patients as the SLE progresses and the factors that predict them. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006134
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To assess prevention of bone loss in women with lupus receiving treatment with glucocorticoids Condition(s): Lupus Study Status: This study is currently recruiting patients.
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Sponsor(s): Genelabs Technologies Purpose - Excerpt: The purpose of this clinical trial is to study the effects of GL701 (which contains DHEA, a mild androgenic hormone, as its active ingredient) on bone mineral density in women with active systemic lupus erythematosus (SLE) who are also receiving treatment with glucocorticoids (e.g., prednisone). Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053560 •
Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases Condition(s): Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis Study Status: This study is no longer recruiting patients. Sponsor(s): Fairview University Medical Center Purpose - Excerpt: Objectives: I. Determine whether there is prompt engraftment after autologous peripheral blood stem cell transplantation using filgrastim (G-CSF) mobilization in patients with life threatening autoimmune diseases. II. Determine the kinetics of T- and B-cell immune reconstitution after a combination of timed plasmapheresis, high dose cyclophosphamide and total lymphoid irradiation, and posttransplant immunosuppression with cyclosporine in these patients. III. Determine whether this treatment regimen beneficially influences the clinical course of these patients. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006055
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Drug Therapy in Lupus Nephropathy Condition(s): Nephrotic Syndrome; Systemic Lupus Erythematosus Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Purpose - Excerpt: Studies have shown that up to 26% of patients with systemic lupus erythematoses nephritis may suffer from membranous lupus nephropathy. The disease is characterized by high levels of protein in the urine and may eventually lead to kidney failure. This study will evaluate the effectiveness and toxic effects of immunosuppressive drug therapy in patients with membranous lupus nephropathy over a 12 month period. The major goal of this therapy is to decrease protein losses and ultimately prevent kidney failure. Patients enrolled in the study will undergo a routine history and physical examination. In addition, several diagnostic tests will be conducted including; chest x-ray ECG, blood and urine laboratory tests. Patients will be divided and grouped according to the severity of their disease as shown by kidney function.
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Each group will then randomly be subcategorized by different treatment plans. Each treatment plan will made up of immunosuppressive medications including prednisone, cyclophosphamide, cyclosporin A, and combinations of these drugs. Patients will receive the medications as directed by the study. The study will last 12 months and require patients to be admitted for two to five days before the study begins and once the study is completed. Patients will be followed as outpatients throughout the 12 month study. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001212 •
Safety of Estrogens in Lupus: Birth Control Pills Condition(s): Systemic Lupus Erythematosus Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Office of Research on Women's Health (ORWH) Purpose - Excerpt: Safety of Estrogens in Lupus Erythematosus - National Assessment (SELENA) is a study to test whether women with systemic lupus erythematosus (SLE or lupus) can safely use estrogen. We will determine this by looking at the effects of oral contraceptives (birth control pills, also known as "the pill") on disease activity and severity in women with SLE. The results of the study will show whether it is safe for women with SLE to use the pill. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000420
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Serologically Active, Clinically Stable Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: The first part of this study will use the database of a large, ongoing NIH-sponsored lupus study, Safety of Estrogen in Lupus Erythematosus National Assessment. We will examine the levels of a blood protein known as C3a in a series of patient blood samples to see if C3a levels predict lupus flares or are better than other blood tests, and therefore should be used more widely in managing lupus. In the second part of the study we will add or increase prednisone treatment on the basis of abnormalities in blood tests for C3a and dsDNA antibodies. Early treatment based on increases in C3a and dsDNA antibodies, before the patient develops physical signs of disease, may reduce lupus flares and, ultimately, the patient's total steroid exposure. We will follow study participants for 1 year on a monthly basis and do full physical examinations and laboratory evaluations. If C3a and dsDNA antibody levels are increased significantly above baseline levels while a patient is clinically stable, we will
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give the patient either prednisone or an inactive pill (placebo) for 1 month. We will follow these patients monthly to compare how often lupus flares occur in the two groups. This approach could provide a novel method of preventing lupus flares, using C3a as a sensitive predictor of flare. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000421 •
A Pilot Trial of Topical Thalidomide for the Management of Chronic Discoid Lupus Erythematosus Condition(s): Discoid Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: The purpose of this double-masked, pilot trial is to determine whether 20 percent thalidomide ointment is safe and effective for the treatment of chronic discoid lupus erythematosus (CDLE) when used under an occlusive dressing. Seventeen patients with two similar lesions will have lesions randomized to receive either intervention or placebo therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001680
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Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Condition(s): Lupus Erythematosus, Systemic Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: High cholesterol levels are common in people with Systemic Lupus Erythematosus (SLE). Atorvastatin is a drug that reduces cholesterol levels. This study will test whether atorvastatin can reduce cholesterol levels in children with SLE. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065806
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BG9588 (Anti-CD40L Antibody) to Treat Lupus Nephritis Condition(s): Glomerulonephritis, Membranoproliferative; Lupus Nephritis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
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Purpose - Excerpt: The purpose of this study is to investigate whether the experimental drug BG9588 can be used to treat lupus nephritis more effectively and with less toxicity than standard treatments, including cyclophosphamide (Cytoxan), azothioprine (Imuran) and prednisone. The body's immune system naturally produces antibodies to fight foreign substances like bacteria and viruses. In autoimmune diseases like lupus, however, the body makes antibodies that attack its own tissues, causing inflammation and organ damage. Lupus antibodies attack and damage kidney cells. BG9588 can interfere with the production of these antibodies, and therefore, may lessen kidney damage in people with lupus nephritis. This study will look at: how BG9588 enters and leaves the blood and body tissue over time; adverse effects of the drug; and whether treatment with BG9588 can result in less kidney damage than other therapies. Study patients will be receive a 30-minute infusion of BG9588 into a vein every two weeks for three doses and then once every 28 days for four doses. Patients' steroid dosage may be tapered; individual adjustments will be made as required. Patients screened for the study will undergo a physical examination, medical history, various blood and urine tests, as well as complete a quality of life questionnaire. Results of a previous kidney biopsy and chest X ray are also required. Many of these tests will be repeated throughout the study. In a previous animal study, BG9588 treatment of mice with lupus nephritis improved their disease and survival. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001789 •
Cyclophosphamide and Fludarabine to Treat Lupus Nephritis Condition(s): Glomerulonephritis; Lupus Nephritis; Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will test the safety and effectiveness of combination therapy with cyclophosphamide (Cytoxan) and fludarabine in treating lupus nephritis (kidney inflammation). This condition, common in patients with systemic lupus erythematosus, is caused by abnormal action of immune cells called lymphocytes against the kidneys. Left untreated, severe cases can result in loss of kidney function. The current treatment of choice-intermittent high doses (pulses) of cyclophosphamidedoes not work in all patients and causes infertility in many women. The rate of infertility in men is not known. This study will examine whether fludarabine can safely be given with significantly lower doses of cyclophosphamide, and if this combination controls kidney inflammation. Patients 18 years of age and older with severe lupus nephritis (called proliferative lupus nephritis) may be eligible for this study. Candidates will have a history and physical examination; blood and urine tests; chest X-ray; electrocardiogram; cancer screening that may include a Pap smear, mammogram, rectal examination, PSA testing, and sigmoidoscopy. Participants will be divided into one of the following treatment groups: Group 1-Patients undergo three treatment cycles of cyclophosphamide, taken by mouth, and fludarabine, injected subcutaneously (under the skin). Patients receive both drugs on day 1 of the cycle, and fludarabine alone on days 2 and 3. This regimen is repeated once every 5 weeks for three cycles. Group 2Same as for Group 1, except fludarabine injections are given intravenously (through a
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vein) for the second treatment cycle. Patients in this group have frequent blood sampling during the first and second treatment cycles to monitor blood levels of the drug. Samples are collected before the first injection is given and at 0.5, 1, 1.5, 2, 4, 8, 24 and 48 hours after the third injection. A total 12 tablespoons of blood is drawn over a 2month period. All patients will have blood drawn once or twice a week during the first two cycles and then less frequently to monitor blood counts. Some patients will have the following additional procedures to test the effects of treatment on lymphocytes: 1. Blood sample collection 2. Bone marrow aspiration-The skin over the hip bone is cleaned and a local anesthetic is injected into the outer covering of the bone. Bone marrow is suctioned through the needle into an attached syringe. The procedure is done before treatment begins, at the end of treatment, and 6 months after treatment. 3. Tonsillar biopsy-The tonsils are numbed with a local anesthetic and 1 to 4 pieces of tissue are removed using special forceps. The procedure is done before treatment begins, at the end of treatment, and 6 months after treatment. 4. Magnetic resonance imaging (MRI) of the abdomen-The patients lies on a table in a narrow cylinder (the MRI scanner) containing a strong magnetic field, which is used to create images of parts of the body in small section views. Patients will be followed for at least 24 months to monitor late side effects and the response to treatment. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001676 •
Epidemiologic Study of Reproductive Outcome in Women with Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Northwestern University Purpose - Excerpt: Objectives: I. Evaluate whether pregnancy is an independent risk factor that affects disease activity in women with systemic lupus erythematosus. II. Evaluate whether maternal disease activity is a risk factor for adverse pregnancy outcome. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004663
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High-Dose Intravenous Cyclophosphamide
(IV)
Cyclophosphamide
Versus
Monthly
IV
Condition(s): Lupus Erythematosus, Systemic Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study compares the effectiveness of high-dose cyclophosphamide treatment with the "gold standard" treatment, monthly intravenous (IV) cyclophosphamide, in people with moderate to severe lupus that does not respond
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to high-dose corticosteroid therapy. We will give patients either IV cyclophosphamide (750 milligrams per square meter of body surface area) monthly for 6 months, followed by quarterly maintenance therapy, or high-dose IV cyclophosphamide (50 milligrams per kilogram body weight per day) for the first four days of the study. Patients will be followed for 24 months after therapy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005778 •
Humanized LL2IGG to Treat Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will examine the safety of a new genetically engineered antibody called hLL2 (epratuzumab) in patients with systemic lupus erythematosus (SLE). It will also evaluate whether hLL2 can lessen overall disease activity in SLE or kidney damage in patients with lupus nephritis. Patients 18 years of age and older with mild to moderately active SLE may be eligible for this study. Candidates will be screened with blood and urine tests, a chest X-ray, electrocardiogram (EKG), tuberculin skin test, and screening tests for certain cancers. All participants will receive weekly infusions of hLL2 for 4 weeks. The drug is given through a catheter (small plastic tube) placed through a needle in an arm vein. Each infusion takes about 2 hours, after which the patient is observed in the clinic for 1 to 2 hours before being discharged from the clinic. The first 3 patients in the study will receive the lowest of three different doses used in the study. If this dose is well tolerated, the next 5 patients will receive a higher dose. If the second dose is tolerated, the last 5 patients will be given the highest dose. If any serious problems are encountered at a dose, patients in the next group will receive either the same or lower dose before being advanced to the next level. Patients in the first group will continue taking prednisone at their regular dose. All other patients will have their prednisone tapered gradually, if their condition permits. Patients who have a disease flare may have their prednisone increased for up to 2 weeks, followed by a gradual taper. If the flare is severe or does not respond to the increased prednisone, the patient will be taken off the study and treated to control the disease. Patients will be evaluated at various intervals for up to 8 weeks after the last dose. Several of the screening tests will be repeated throughout the study. No more than 500 ml of blood-the equivalent of a single blood donation-will be collected during a 2-month period. Participants may also be asked to undergo the following optional procedures before starting treatment, 1 week after the last dose and 8 weeks after the last treatment dose: Bone marrow aspiration - to collect cells from the bone marrow. The hip area is anesthetized and a special needle is used to draw bone marrow from the hipbone. Tonsil biopsy - The area to be biopsied is numbed with a local anesthetic and small pieces of tissue will be removed with a special type of forceps. (The procedure may be done under general anesthetic.) - Magnetic resonance imaging (MRI) of the abdomen The patient lies on a table within a metal cylinder (the MRI scanner) for about 30 to 40 minutes while images are obtained with the use of a strong magnetic field and radio waves.
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Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011908 •
Improving Quality of Life for African American Female Adolescents With Lupus Condition(s): Lupus Study Status: This study is not yet open for patient recruitment. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will evaluate a program designed to help African American adolescents with lupus (systemic lupus erythematosus or SLE) cope with the disease. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00068874
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Lupus Cohort--Thrombotic Events and Coronary Artery Disease Condition(s): Cardiovascular Diseases; Coronary Disease; Thrombosis; Heart Diseases; Lupus Erythematosus, Systemic Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To study longitudinally the incidence, pathogenesis, and risk factors for thrombotic events and coronary artery disease in a cohort of patients with systemic lupus erythematosus (SLE). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005436
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Phase II Pilot Study of Cytarabine for Refractory Systemic Lupus Erythematosus Condition(s): Lupus Erythematosus, Systemic Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); University of Michigan Purpose - Excerpt: Objectives: I. Evaluate the toxicity of cytarabine in patients with refractory systemic lupus erythematosus. II. Evaluate objective disease parameters, including serum complement levels, anti-DNA antibody titers, sedimentation rate, and the systemic lupus activity measure in these patients. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004643
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Phase II Study of Long-Term Dehydroepiandrosterone for Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Northwestern University Purpose - Excerpt: Objectives: I. Evaluate the long-term safety and tolerance of a synthetic formulation of dehydroepiandrosterone, GL701, in patients with systemic lupus erythematosus who have completed a prior GL701 protocol. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004665
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Phase II/III Randomized, Double-Blind, Placebo-Controlled Study of Dehydroepiandrosterone in Women with Mild to Moderate Systemic Lupus Erythematosus Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Northwestern University Purpose - Excerpt: Objectives: I. Evaluate the safety and efficacy of synthetic dehydroepiandrosterone (GL701) in women with prednisone-dependent systemic lupus erythematosus. II. Describe the pharmacokinetics of GL701. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004795
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Phase III Randomized, Double-Blind, Placebo-Controlled Study Dehydroepiandrosterone in Women with Active Systemic Lupus Erythematosus
of
Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Northwestern University Purpose - Excerpt: Objectives: I. Evaluate the safety and efficacy of synthetic dehydroepiandrosterone, GL701, in women with active systemic lupus erythematosus. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004662 •
Positron Emission Tomography (PET) to Locate Areas of White Blood Cell Activity Condition(s): Lupus Erythematosus; Systemic Study Status: This study is completed.
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Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: This study will examine whether PET imaging can reveal what is happening in lymph nodes of patients with systemic lupus erythematosus, or lupus, during periods of active disease. Patients may have periods of active disease when they may feel sick with fever, fatigue, and aching or swollen joints. Their blood tests are abnormal and their kidney, lungs or heart may be affected. At other times, the disease is inactive, and patients feel well, their blood is normal, and there is no evidence of organ disease. In lupus, like other autoimmune diseases, the body's immune system attacks it own healthy tissues. Activated lymphocytes (a type of immune cell) lead to the production of antibodies and chemical signals that contribute to the disease process. In animals with lupus, these cells are activated in the lymphoid organs, such as the lymph nodes or spleen. It is not known exactly where these cells are activated in humans. Because some lymph nodes are located deep inside the chest and abdomen; surgery is currently the only way to examining them. PET imaging may provide an alternative, non-invasive, means of obtaining information on lymph node activity in humans. This test uses a radioactive sugar molecule called F18-FDG to find areas of increased cellular activity in the body. (Cells use sugar for fuel, so active cells, such as active lymphocytes, uses more FDG than other body tissues.) This study will determine whether PET can detect these areas of increased activity in lupus during active disease. Patients with active or inactive lupus may be eligible for this study. Candidates are screened with a history, physical examination, and routine blood and urine tests. Women who are pregnant or breastfeeding may not participate. Participants will undergo PET scanning. On the day of the scan they have a brief medical history and physical examination and a blood sample is drawn to check blood count and look for markers of lymphocyte activation. Then, a small plastic tube (catheter) is placed into a vein in the patient's arm, the FDG is injected through the catheter, and the patient rests for an hour. For the scan, the patient lies flat in a cradle that is moved into the central hole of the doughnutshaped PET camera, and pictures are taken over the next 2 hours, with the patient lies quietly, without moving the head or arms. After the scan is finished, the patient empties the bladder approximately every hour for 6 hours to excrete the radioactive sugar. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029926 •
Prevention of Arthritis-Related Work Disability Condition(s): Rheumatoid Arthritis; Systemic Lupus Erythematosus; Osteoarthritis, Knee; Ankylosing Spondylitis Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: People with rheumatic disorders (arthritis) often have trouble keeping their jobs. This study will look at whether vocational rehabilitation (VR) will improve the ability of employed people with arthritis to keep their jobs. Job retention VR services target key factors that increase the risk of job loss. They aim to modify jobs to reduce barriers caused by functional limitations and disease symptoms, future career planning, and establish a partnership with a VR counselor for ongoing help. We will conduct the study among patients with rheumatic disorders recruited in eastern
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Massachusetts. We will give 120 study participants job retention services provided by VR counselors. We will give another 120 participants literature about employmentrelated resources. We will compare the outcomes of the two groups to evaluate the usefulness of job retention services in preventing job loss in people with rheumatic disorders. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000416 •
Psychoeducational Approach to Improve Health in Lupus Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: We will study the relationships among patient/partner communication, social support, and self-efficacy (a person's belief in the ability to manage his or her disease) as they affect the health of people with systemic lupus erythematosus (SLE, or lupus) over time. We are assigning 150 people with lupus and their partners to either (1) receive counseling to improve self-efficacy, partner support, and patient/partner problem solving or (2) see an informational film about lupus. We will follow study participants for 12 months to find out about their physical and mental health, disease activity, beliefs that they can take steps that help them feel better, coping, social support, and couples communication. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000417
•
Safety and Efficacy Study of LJP 394 (abetimus sodium) to treat lupus kidney disease Condition(s): Immunologic Diseases; Autoimmune Diseases; Erythematosus; Lupus Nephritis; Lupus Glomerulonephritis
Systemic
Lupus
Study Status: This study is completed. Sponsor(s): La Jolla Pharmaceutical Company Purpose - Excerpt: The purpose of this study is to determine whether LJP 394 (abetimus sodium) is safe and effective in delaying and reducing renal flares in patients with lupus nephritis. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035308
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•
Safety of Estrogens in Lupus: Hormone Replacement Therapy Condition(s): Systemic Lupus Erythematosus Study Status: This study is terminated. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Office of Research on Women's Health (ORWH) Purpose - Excerpt: Safety of Estrogens in Lupus Erythematosus - National Assessment (SELENA) is a study to test whether postmenopausal women with systemic lupus erythematosus (SLE, or lupus) can safely use the hormone estrogen. In this part of the study, we will look at the effects of estrogen replacement therapy on the activity and severity of disease in women with SLE. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000419
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Study of Individualized Erythematosus
Instruction
versus
Pamphlet
in
Systemic
Lupus
Condition(s): Systemic Lupus Erythematosus Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Virginia Commonwealth University Purpose - Excerpt: Objectives: I. Evaluate an educational program that has been pretested for cultural appropriateness and literacy requirements in patients with systemic lupus erythematosus (SLE). II. Assess the impact of this educational program on patients with SLE, with an emphasis on recognizing cardinal symptoms, coping with fatigue, regulating medications, and communicating with the physician. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004756
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “lupus” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical
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trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON LUPUS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “lupus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lupus, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Lupus By performing a patent search focusing on lupus, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We
9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on lupus: •
Conjugates of biologically stable polyfunctional molecules and polynucleotides for treating systemic lupus erythematosus Inventor(s): Coutts; Stephen (San Diego, CA), Conrad; Michael J. (San Diego, CA) Assignee(s): La Jolla Pharmaceutical Company (San Diego, CA) Patent Number: 5,276,013 Date filed: July 15, 1992 Abstract: Chemically defined conjugates of biologically stable valency platform molecules, such as copolymers of D-glutamic acid and D-lysine or polyethylene glycol, and polynucleotide duplexes of at least 20 base pairs that have significant binding activity for human lupus anti-dsDNA autoantibodies. The duplexes are preferably homogeneous in length structure and are bound to the valency platform molecule via reaction between a functional group located at or proximate a terminus of each duplex and functional groups on the valency platform molecule. These conjugates are tolerogens for human systemic lupus erythematosus. Excerpt(s): A preferable approach to SLE treatment would be to administer a drug that is capable of reestablishing immune tolerance to the autoantigens involved in SLE without affecting the normal functions of the immune system. Unfortunately, there is no current way of treating SLE, or for that matter any autoimmune disorder, that is benign and specific to the disease-associated autoantigens. The conjugates of the invention are a means for providing such treatment for SLE. Benacerraf, Katz, and their colleagues investigated and described the use of conjugates of D-glutamic/D-lysine, referred to as D-GL in earlier literature, (herinafter "D-EK"); with haptens and various antigens to induce specific immune tolerance. Their initial studies involved conjugates of the synthetic hapten 2,4-dinitrophenyl (DNP) in guinea pigs and mice and showed that the conjugates could induce tolerance to DNP. These initial studies were extended to other haptens/antigens such as ragweed antigen E and benzylpenicilloyl (BPO). See U.S. Pat. Nos. 4,191,668 and 4,220,565. U.S. Pat. No. 4,191,668 (Example IV) describes the preparation of conjugates of D-EK and oligonucleotides isolated from DNAse 1-digested calf thymus DNA. The oligonucleotides were characterized as being composed of "fewer than 10 nucleotides." Although column 11 of U.S. Pat. No. 4,191,668 indicates that its invention has therapeutic value for treatment of autoimmune disease and mentions SLE, no data are presented on the immunological effects of the mentioned D-EKoligonucleotide conjugates. Web site: http://www.delphion.com/details?pn=US05276013__
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Conserved anti-DNA antibody idiotype associated with nephritis in murine and human lupus Inventor(s): Weisbart; Richard (Los Angeles, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,232,444 Date filed: April 8, 1996
Patents 317
Abstract: Methods and antibody compositions are provided for the diagnosis and treatment of lupus nephritis. By employing B-cells of a lupus nephritis host with a fusion partner, antibodies can be obtained, which may serve as immunogens for the production of antiidiotypic antibodies, which may then be used for diagnosis and therapy of lupus nephritis. Excerpt(s): The field of this invention is the diagnosis and treatment of nephritis associated with systemic lupus erythematosus. Antibodies to deoxyribose nucleic acid (DNA) are the hallmark of systemic lupus erythenotesus (SLE) and are associated with the development of kidney disease (nephritis). However, anti-DNA antibodies are heterogeneous and the structural basis for pathogenic anti-DNA antibodies has remained elusive. Idiotypes are structural determinants on or near antibody binding sites recognized by a second (antiidiotype) antibody. Antiidiotype antibodies can be used to identify unique structural features of potentially pathogenic anti-DNA antibodies. Although several anti-DNA antibody antiidiotypes have been produced, an anti-idiotype has not been produced that characterizes unique structural features of antiDNA antibodies that are conserved in both murine and human lupus associated with nephritis. Because of the substantial interest in being able to diagnose and treat lupus associated with nephritis, various efforts have been made to determine the causative agent of nephritis associated lupus and to find therapeutic techniques. It is therefore of interest to be able to develop antibodies which are capable of recognizing disease related anti-DNA antibodies. Web site: http://www.delphion.com/details?pn=US06232444__ •
Diagnostic method for detection of systemic lupus erythematosus Inventor(s): Kallick; Charles A. (181 W. 135 St., Lemont, IL 60439) Assignee(s): none reported Patent Number: 4,329,331 Date filed: March 13, 1980 Abstract: Systemic lupus erythematosus is diagnosed by contacting the blood serum of a patient with anaplasma antigen derived from a vertebrate infected by an organism of the genus Anaplasmataceae and thereafter contacting the antigen with an indicator for human immunoglobulin components. Excerpt(s): This invention relates to disease detection, and particularly to a method for diagnosis and detection of systemic lupus erythematosus. Lupus erythematosus is a disease which is more prevalent than is generally recognized. Discoid lupus erythematosus, which affects the skin, is generally recognized by its particular type of skin rash, although mild cases are frequently unrecognized. Systemic lupus erythematosus (hereinafter SLE), which may or may not be associated with skin lesions, may be associated with joint pains resembling those of arthritis, or may be associated with other symptoms or conditions, such as pleurisy, anemia or kidney involvement. With symptoms so varied, it is understandable that SLE is frequently misdiagnosed and unrecognized. Web site: http://www.delphion.com/details?pn=US04329331__
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•
Genetic marker test for lupus Inventor(s): Tsao; Betty P. (Los Angeles, CA), Cantor; Rita M. (Rolling Hills Estates, CA), Rotter; Jerome I. (Los Angeles, CA) Assignee(s): Cedars-Sinai Medical Center (Los Angeles, CA), The Regents of the University of California (Oakland, CA) Patent Number: 6,280,941 Date filed: March 29, 1999 Abstract: Disclosed is a genetic testing method for diagnosing systemic lupus erythematosus (SLE) in a human subject. The method is related to amplifying nucleic acids from human tissue samples and analyzing for a variant allele of a gene encoding poly(ADP-ribosyl)transferase expression (PARP), which is diagnostic of SLE or indicates a genetic predisposition for developing SLE. Also disclosed are useful oligonucleotide primers, primer sets and genetic testing kits for detecting a genetic predisposition for developing SLE. Excerpt(s): Throughout this application various publications are referenced within parentheses. The disclosures of these publications in their entireties are hereby incorporated by reference in this application in order to more fully describe the state of the art to which this invention pertains. This invention relates to the medical arts. In particular, it relates to a method of detecting a genetic predisposition to systemic lupus erythematosus. Systemic lupus erythematosus (SLE), commonly known as lupus, is an autoimmune rheumatic disease characterized by deposition in tissues of autoantibodies and immune complexes leading to tissue injury (B. L. Kotzin, Systemic lupus erythematosus, Cell 85:303-06 [1996]). In contrast to autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus, SLE potentially involves multiple organ systems directly, and its clinical manifestations are diverse and variable. (Reviewed by B. L. Kotzin and J. R. O'Dell, Systemic lupus erythematosus, In: Samler's Immunologic Diseases, 5th ed., M. M. Frank et al., eds., Little Brown & Co., Boston, pp. 667-97 [1995]). Web site: http://www.delphion.com/details?pn=US06280941__
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Identification of an exogenous intra-erythrocytic bacterium in patients having systemic lupus erythematosus, and treatment Inventor(s): Kallick; Charles A. (16411--135th St., Lemont, IL 60439) Assignee(s): none reported Patent Number: 5,972,309 Date filed: August 11, 1998 Abstract: Intra-erythrocytic exogenous bacterial structures or parasites seen by giemsa and phase contrast microscopy in several patients with systemic lupus erythematosus (SLE) and not in controls were identified as bacteria. Treatment of an SLE patient is contemplated with an antibacterial amount of a rifamycin in conjunction with an antibacterial amount of either a macrolide such as clarithromycin or a third generation cephalosporin such as cefpodoxime that is itself more preferably used in conjunction with an adjuvant amount of probenecid. Excerpt(s): The present invention relates to identification of the presence of an exogenous structure within human erythrocytes or bone marrow cells and treatment thereof, and more particularly to an assay for the presence of an exogenous bacterial
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structure or parasite within the erythrocytes of patients having systemic lupus erythematosus (SLE) and treatment of such patients to lessen or eliminate the erythrocytic or bone marrow load of those bacterial structures. Systemic lupus erythematosus (SLE) is a protean disease of unknown etiology which affects multiple organs. Lahita, R. G. Systemic Lupus Erythematosus, Churchill, Livingston, N.Y. (1987) page XXIX. Although there is a marked similarity to an infectious entity, an exhaustive search for an etiologic agent has not yielded any proven candidates that fulfill the criteria for causation of this disease. Crow et al., "Etiologic Hypothesis for Systemic Lupus Erythematosus," in Lahita Systemic Lupus Erythematosus, Churchill, Livingston, N.Y. (1987) page 51 ff. There is general agreement that tissue and organ injury in SLE is mediated by immune phenomena. Unexplained at this time is the predilection of SLE for females. Taurog et al., Intern. J. Derm., 20:149-158 (1981). Early descriptions of SLE before the advent of suppressive therapy suggested sepsis, and included fever, striking constitutional symptoms and high mortality. Crow et al., "Etiologic Hypothesis for Systemic Lupus Erythematosus," in Lahita Systemic Lupus Erythematosus, Churchill, Livingston, N.Y. (1987) page 54. Recently, many viral etiologic agents have been sought; none have been convincingly demonstrated. Pincus, Arthr & Rheum, 20:149-158 (1982). More recently the characterization of soluble products of bacteria and mycoplasmas with unique capacities to perturb immune systems have led to new considerations in regard to the infectious trigger of SLE. Web site: http://www.delphion.com/details?pn=US05972309__ •
Kidney extract for treatment of systematic lupus erythematosus Inventor(s): Ofosu-Appiah; William (New Hartford, NY) Assignee(s): Masonic Medical Research Laboratory (Utica, NY) Patent Number: 5,695,785 Date filed: June 27, 1996 Abstract: The invention is directed to a method of treating systematic lupus erythematosus (SLE) in animals, including humans, by the oral administration of kidney extracts to decrease anti-DNA antibody production. The method of the invention includes both prophylactic and therapeutic measures. Excerpt(s): The present invention relates to a method of treating systematic lupus erythematosus (SLE) in mammals. Specifically, the present invention provides the oral administration of kidney extracts for the prophylactic and therapeutic treatment of SLE. Systemic lupus erythematosus is an autoimmune disease which is not specific to any organ. This disease affects a large number of organs and has a chronic course with acute episodes. The external manifestations of SLE are lesions on the facial skin. In most cases, other areas of skin and the mucosa are affected. Also observed are nephritis, endocarditis, hemolytic anemia, leukopenia and involvement of the central nervous system. Many immunological phenomena have been observed with SLE. For example, the formation of antibodies against certain endogenous antigens has been seen. These antibodies are directed against, for example, the basement membrane of the skin, and against lymphocytes, erythrocytes and nuclear antigens. Antibodies which are directed against double-stranded DNA (ds-DNA) form with the latter complexes. These antibodies, together with complement, are deposited on small blood vessels and frequently result in vasculitis. These deposits are especially dangerous when they occur in the renal glomeruli because they result in glomerulonephritis and kidney failure. The
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incidence of clinically detectable kidney involvement is reported in the literature to be between 50 and 80%. Web site: http://www.delphion.com/details?pn=US05695785__ •
Localization of major peptide autoepitopes for nucleosome specific T cells of systemic lupus erythematosus Inventor(s): Kaliyaperumal; Arunan (Skokie, IL), Datta; Syamal K. (Winnetka, IL) Assignee(s): The Board of Trustees of Northwestern University (Evanston, IL) Patent Number: 6,468,537 Date filed: April 28, 2000 Abstract: The present invention includes peptides derived from nucleosomal histone proteins which are useful for delaying the onset and progression of systemic lupus erythematosus (i.e. lupus or SLE). The peptides of the invention span the histone proteins (i.e. H1, H2A, H2B, H3, and H4). The invention additionally encompasses isolated nucleic acids which encode these histone peptides as well as pharmaceutical compositions which comprise one or more of a histone peptide. Further, the invention provides kits which comprise one or more histone peptides or isolated nucleic acids encoding histone peptides and an instructional material. The invention also provides methods of using these compositions and analogs of histone peptides to inhibit an immune response and associated inflammation in an animal and to treat disorders in an animal which are related to the production of autoantibodies and complications thereof, such as inflammatory diseases, autoimmune disorders, and nephritis. Excerpt(s): Nucleosome-specific T helper cells (Th cells) initiate and sustain the production of pathogenic, anti-nuclear autoantibodies during the onset and progression of systemic lupus erythematosus (SLE) through cognate interaction with autoimmune B cells (Mohan et al., 1993, J. Exp. Med. 177:1367; Desai-Mehta et al., 1995, J. Clin. Invest. 95:53; Kaliyaperumal et al., 1996, J. Exp. Med. 183:2459; Shi et al., 1998, J. Exp. Med. 187:367; Voll et al., 1997, Arthritis Rheum. 40:2162; Kretz-Rommel, et al., 1997, J. Clin. Invest. 99:1888). These SLE-associated Th cells are primarily responsible for driving the pathogenic autoimmune response. Without the help provided by these Th cells, autoimmune B cells are unable to produce the disease-causing (pathogenic) autoantibodies associated with SLE. Some of the critical epitopes (i.e. autoantigenic determinants) to which these Th cells are directed have been localized to the histone proteins of nucleosomes (i.e. DNA-protein complexes in the nuclei of animal cells). For example, in lupus prone mice, SLE-associated autoepitopes have been identified at amino acid positions 10-33 of the H2B histone protein, at amino acid positions 85-102 of the H3 histone protein, and at amino acid positions 16-39 and 71-94 of the H4 histone protein (Kaliyaperumal et al., 1996, J. Exp. Med. 183:2459). Autoimmune T cells of lupusprone mice are spontaneously primed to SLE-associated autoepitopes early in life before overt autoantibody production or any clinical manifestations of the disease are present (Kaliyaperumal et al., 1996, J. Exp. Med. 183:2459). Moreover, immunization of preautoimmune mice with peptides corresponding to SLE-associated nucleosomal autoepitopes precipitates SLE-associated nephritis by triggering autoimmune T helper cells of subtype 1 (i.e. Th 1 cells) which, in turn, initiate anti-nuclear autoantibody production (Kaliyaperumal et al., 1996, J. Exp. Med. 183:2459). The T helper cell subtypes 2 and 0 (i.e., Th2 and Th0 cells, respectively) are also involved in the progression of SLE, as these T helper cell subtypes maintain autoantibody production (Mohan et al., 1993, J. Exp. Med. 177:1367; Nakajima et al., 1997, J. Immunol. 158:1466).
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Unlike organ-specific autoimmune diseases in which the autoimmune response targets a restricted set of autoepitoes and is mediated by a single population of T cells, the autoimmune response in SLE involves a complex web of polyclonal T cell and B cell hyperactivity and appears to be directed by multiple susceptibility genes (Datta et al., 1982, J. Immunol. 129:1539; Klinman and Steinberg, 1987, J. Exp. Med. 165:1755; Cohen and Eisenberg, 1991, Ann. Rev. Immunol. 9:243; Chan and Shlomchik, 1998, J. Immunol. 160:51; Jongstra-Bilen, 1997, J. Immunol. 159:5810; Mohan et al., 1995, J. Immunol. 154:1470; Desai-Mehta, 1996, J. Clin. Invest. 97:2063; Koshy et al., 1996, J. Clin. Invest. 98:826; Liossis, et al., 1996, J. Clin. Invest. 98:2549; Wakeland et al., 1997, J. Clin. Immunol. 17:272; Vyse and Kotzin 1996, Opin. Immunol. 8:843; Kono and Theofilopoulos, 1996, J. Autoimmunity 9:437). Web site: http://www.delphion.com/details?pn=US06468537__ •
Lupus disease immunoassay methods Inventor(s): Naparstek; Yaakov (Jerusalem, IL) Assignee(s): Hadasit Medical Research Services & Development Co., Ltd. (Jerusalem, IL) Patent Number: 5,789,260 Date filed: September 17, 1996 Abstract: The invention provides an immunoassay reagent for the binding and detection of antibodies found in the urine of lupus disease patients, comprising extracellular matrix. Excerpt(s): The present invention relates to immunoassay reagents, kits and methods. More particularly, the present invention relates to a novel reagent for binding and detection of antibodies found in the urine of lupus disease patients, and to kits and methods incorporating the same. Systemic lupus erythematosus (SLE) is a disease of unknown etiology, in which tissues and cells are damaged by deposition of pathogenic autoantibodies and immune complexes. Ninety percent of cases are in women, usually of childbearing age, but children, men, and the elderly can be affected. In the United States, the prevalence of SLE in urban areas varies from 15 to 50 per 100,000; it is more common and more severe in blacks than in whites. Hispanic and Asian populations are also susceptible. Web site: http://www.delphion.com/details?pn=US05789260__
•
Method for the determination of lupus anticoagulant antibodies that cause thrombosis Inventor(s): Seelig; Christoph (Asslar, DE), Muller-Berghaus; Gert (Giessen, DE), Potzsch; Bernd (Giessen, DE) Assignee(s): Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.V. (Gottingen, DE) Patent Number: 5,610,024 Date filed: March 29, 1995 Abstract: In order to determine lupus anticoagulant (LA) antibodies in blood, plasma or tissue samples by means of the inhibitory effect of these antibodies on the neutralizing effect of protein C on the blood coagulation system, a defined amount of activated
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protein C is added to the sample, after incubation the remaining amount of a physiological substrate of protein C or protein S activity in the sample is determined according to known methods and the amount of LA antibodies present is calculated by comparison with a standard containing no LA antibodies. The method according to the present invention can be used to diagnose a predisposition to thrombotic events or disease-dependent risk of thrombosis as well as to monitor a therapy. Excerpt(s): The invention concerns a method for the determination of LA antibodies (lupus anticoagulant) in blood, plasma, plasma fractions and tissue extracts by their influence on the phospholipid-dependent anticoagulant activity (anticoagulant activity, anticoagulatory activity) of activated protein C (APC). The method according to the present invention can be used to diagnose certain predispositions or diseases, to monitor the course of a disease or to monitor a therapy. Antiphospholipid antibodies (aPL) are autoantibodies which occur in persons in association with arterial and/or venous occlusions, thrombocytopenia and/or stontaneous abortions (reference: Lechner, K., Pabinger-Fasching, I., Haemostasis 15 (1985), 254-262; Branch, D. W. et al., N. Engl. J. Med. 313 (1985), 1322-1326; Exner, T., Thromb. Haemostas. 53 (1985), 15-18). aPLs can be detected by various tests e.g. by an ELISA using various phospholipids as the antigen or by conventional flocculation tests. Those aPLs which can be detected by coagulation tests are denoted LA antibodies (lupus anticoagulant). LA antibodies interfere with the phospholipid-dependent clotting steps and therefore prolong the coagulation times of various tests without inhibiting the activity of individual coagulation factors. But they do not represent a uniform group of autoantibodies against a sufficiently defined antigen. Malia et al., British Journal of Haematology 76 (1990), 101-107, mention a possible connection between antiphospholipid antibodies and thrombotic risk. The investigations which led to this finding were carried out on IgG fractions isolated from patient plasma with addition of purified activated protein C as well as of protein S and phosphatidylserine and phosphatidylcholine. This led to the conclusion that antiphospholipid antibodies have an inhibitory effect on complexes of activated protein C and protein S. However, it is not possible using the tests available up to now to predict with sufficient certainty and rapidity for clinical application if a patient with detected aPL really also has a thrombotic risk (reviews: Triplett, D. A., Sem. Thromb. Hemostas. 16 (1990), 182-192; Jouhikainen, T. et al., Blood Coagul. Fibrinol. 3 (1992) 407414). Web site: http://www.delphion.com/details?pn=US05610024__ •
Method for the treatment of systemic lupus erythematosus and primary glomerulonephritis and agent therefor Inventor(s): Sugisaki; Tetsuzo (Urawa, JP), Morisue; Shinichi (Tokyo, JP) Assignee(s): Dainippon Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 4,465,670 Date filed: July 23, 1982 Abstract: A method for the treatment of diseases such as systemic lupus erythematosus and primary glomerulonephritis by administering a.gamma.-globulin having Fc fragment to patients suffering from such diseases in parenteral route (particularly intravenously) and a preparation useful for the treatment. The.gamma.-globulin having Fc fragment is usually used in the form of a preparation thereof in admixture with a conventional liquid carrier on diluent for injection, including a plasmin-treated
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human.gamma.-globulin preparation, a sulfonated human.gamma.-globulin preparation and a polyethylene glycol-treated human.gamma.-globulin preparation. Excerpt(s): The present invention relates to a method for the treatment of diseases such as systemic lupus erythematosus and primary glomerulonephritis by administering a.gamma.-globulin having Fc fragment to patients suffering from such diseases by parenteral route, particularly by intravenous route, and also an agent useful for the treatment. It is well known that.gamma.-globulin preparations are useful as an agent in supplementary therapy of primary immune disorder and in passive immunotherapy for the prevention of viral infections and for the treatment of severe infections wherein they are used together with antibiotics, and such preparations are commercially available. Such diseases as systemic lupus erythematosus and primary glomerulonephritis are usually treated by using cortico-steroids or cytotoxic agents. However, these drugs are not effective for fundamental therapy of such diseases and occasionally give serious side effects when they are continuously used for a long period of time. Thus, it has been desired to develop a fundamental therapeutic method effective for such diseases. Web site: http://www.delphion.com/details?pn=US04465670__ •
Method for treatment of Lupus nephritis Inventor(s): Clark; William F. (1132 Richmond Street, London, Ontario, CA), Parbtani; Anwar (418 Rippleton Rd., London, Ontario, CA) Assignee(s): none reported Patent Number: 5,837,256 Date filed: December 19, 1996 Abstract: It has been found that by administering secoisolariciresinol ›2,3-bis(3-methyl4-hydroxybenzyl)butane-1,4-diol! from flaxseed in substantially pure form to a human or non-human animal, lupus nephritis can be controlled. The secoisolariciresinol (Seco) may be used per se or in the form of secoisolariciresinol diglucoside (SDG). Both compounds may be extracted from flaxseed and the SDG converts to Seco in the gut of a human or animal. Excerpt(s): This invention relates to a method for the treatment of lupus nephritis. Lupus nephritis is considered in medical circles to be the "classical" auto-immune disease in which the patient's immune system attacks his/her own organs. It has been estimated that 45-75% of lupus patient's eventually suffer from some form or other of kidney damage. Lupus varies greatly in severity from mild cases requiring minimal intervention to those in which significant damage occurs to vital organs such as lungs, kidneys, heart and brain, and which ultimately can be fatal. Lupus is predominantly a female disease, an approximate female to male ratio being 9:1. In North America, it is estimated to affect 1 in 500 female mainly between the age of 20 to 40 years. Treatment is directed at controlling the symptoms with the hope of putting the disease into remission. There are several chemotherapeutic agents in commercial use and available for remedial purposes. Most of these agents are not without side effects, some of which are severe and debilitating to the patient. Some non-steroidal anti-inflammatory agents may cause stomach upsets and changes in kidney function which can mimic some lupus symptoms themselves. Some anti-malarial drugs, when required at high dosage levels over prolonged time frame, may accumulate in the retina and cause loss of vision. Certain steroidal preparations are used for their anti-inflammatory activity. These can exhibit side effects such as pronounced swelling of the face and abdomen, weight gain,
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excessive growth of body hair, cataracts, osteoporosis and heart attacks. Use of immunosuppressants can have serious side effects such as changes in bone marrow, increased risk of infection to which the body normally shows resistance and a slight increase in the risk of developing certain types of cancer. There is no known cure for lupus. Several reports have appeared in the scientific and medical literature concerning the ability of ground flaxseed to act as a mediator in the partial control of Lupus nephritis. At a level of intake of up to 30 grams per day, ground flaxseed has been shown to reduce the total cholesterol and LDL cholesterol levels by 12% and improve renal function in patients with lupus nephritis ›(Clark, Parbtani et al., (1995) Flaxseed: A potential treatment for lupus nephritis, Kidney International 48: 475-480!. Beyond this intake level, side effects are evident such as Taxation probably due to increased fibre/mucilage intake. Web site: http://www.delphion.com/details?pn=US05837256__ •
Method of detecting ribosomal protein antibodies in systemic lupus erythematosus Inventor(s): Weissbach; Herbert (Cedar Grove, NJ), Skelly; Susan M. (Nutley, NJ), Elkon; Keith (New York, NY), Brot; Nathan (Orange, NJ) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ), Cornell Research Foundation, Inc. (Ithaca, NY) Patent Number: 4,865,970 Date filed: February 28, 1986 Abstract: This invention provides methods for the diagnosis of systemic lupus erythematosus in patients, the sera of which contain antibodies reactive against ribosomal proteins P0, P1 and P2. A peptide containing an amino acid sequence corresponding to the carboxyl termini of the ribosomal proteins, which peptide is bound to a solid carrier, is also provided for use in such methods. Excerpt(s): Systemic lupus erythematosus (SLE) is an autoimmne disease that is characterized primarily by the presence of antibodies against nuclear components. However, about 10-20% of the patients with SLE synthesize antibodies against three ribosomal proteins called P0, P1, and P2. It has been shown that these three proteins contain a common epitope that is recognized by the SLE patients' antibodies. proteins P1 and P2 are thought to be highly conserved in nature and sequencing studies of those proteins isolated from Artemia salina show that the carboxyl terminal 22 amino acids of both proteins are identical. There is no homology, however between the amino terminal residues of these proteins. There is, thus, a need for a reliable and sensitive method of detecting those SLE patients who do not produce antibodies against nuclear components. The present invention is directed to a method of detecting those SLE patients who produce antibodies against ribosomal proteins rather than nuclear components. The method of the invention is, thus, complimentary to existing assays and enables clinicians to detect SLE patients who would not heretofor been detected by existing diagnostic assays. The method of the invention is an immunometric assay wherein an antibody to the ribosomal proteins P0, P1 and P2 present in the biological fluid of an SLE patient will bind to a peptide attached to the solid carrier. A labelled antibody binds to the complex formed when the ribosomal protein antibody binds to the immobilized peptide. The amount of labelled antibody associated with the complex is directly proportional to the amount of antibody substance in the fluid sample. Web site: http://www.delphion.com/details?pn=US04865970__
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Method of treating systemic lupus erythematosus Inventor(s): Warner; Linda M. (North Brunswick, NJ), Adams; Laurel M. (Durham, NC) Assignee(s): American Home Products Corporation (New York, NY) Patent Number: 5,078,999 Date filed: February 22, 1991 Abstract: This invention provides a method of treating systemic lupus erythematosus in a mammal in need thereof which comprises administering an effective amount of rapamycin orally, parenterally, intranasally, intrabronchially, or rectally. Excerpt(s): Systemic lupus erythematosus (SLE), an autoimmune disease primarily affecting young females, is characterized by hyperproliferation of T-lymphocytes; development of autoantibodies directed against nuclear antigens, particularly doublestranded DNA; and immune complex mediated pathology [R. Bartlett, Scand. J. Rheum., 75:290 (1988 Supp.)]. Complexation of the nuclear autoantibodies with their respective antigens, which are subsequently deposited in the small blood vessels, is a direct cause of many of the clinical manifestations of SLE. Clinical manifestations of SLE are observed in almost all organ systems [see, I. McKay, Autoimmune Diseases, Charles C. Thomas, pub., p.70]. These typically include a facial erythematous rash with a "butterfly" distribution over the nose and cheeks. Arthritis and arthralgia most commonly affecting the phalangeal and carpal joints are observed in a majority of SLE patients. Renal involvement is observed in approximately 70% of SLE patients, and is considered to be one of the major causes of mortality from SLE. Glomerulonephritis secondary to the deposition of autoantibody-antigen complex in the kidney, often leads to renal impairment, as observed by proteinuria, or ultimately renal failure. Clinical manifestations of SLE also are observed in the lymphatic, pulmonary, gastrointestinal, hemic, vascular, and central nervous systems. Current treatment of SLE depends on the location and severity of the disease; with the method of treatment often dictated by the organ system affected. Arthritis or arthralgias can often be controlled with aspirin or other non-steroidal anti-inflammatory drugs. More severe manifestations of SLE such as hemolytic anemia, thrombocytopenic purpura, and severe polyserositis have been treated with prednisone. Currently recommended treatment for renal impairment utilizes combinations of prednisone with immunosuppressive agents such as azathioprine or cyclophosphamide. Web site: http://www.delphion.com/details?pn=US05078999__
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Methylated, SMD homologous peptides, reactive with the antibodies from sera of living beings affected with systemic lupus erythematosus Inventor(s): Union; Ann (Aalter, BE), Luhrmann; Reinhard Georg (Marburg, DE), Meheus; Lydie (Merelbeke, BE), Raymackers; Joseph (Eke, BE) Assignee(s): Innogenetics N.V. (Ghent, BE) Patent Number: 6,362,007 Date filed: May 10, 1999 Abstract: The present invention relates to a method of producing certain peptides containing methylated arginines that are followed by a glycine residue and that constitute immunogenic determinants of antibodies present in sera from patients with
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systemic lupus erythematosus, or Epstein-Barr virus and wherein the methylation is a prerequisite for reacting with said antibodies. The invention also relates to the use of said peptides for diagnosis and treatment of systemic lupus erythematosus and related diseases, and diseases in which Epstein-Barr virus has been implicated. Excerpt(s): The present invention relates to a method of producing certain peptides containing methylated arginines that are followed by a glycine residue and that constitute immunogenic determinants of antibodies present in sera from patients with systemic lupus erythematosus, or Epstein-Barr virus and wherein the methylation is a prerequisite for reacting with said antibodies. The invention also relates to the use of said peptides for diagnosis and treatment of systemic lupus erythematosus and related diseases, diseases in which Epstein-Barr virus has been implicated. Systemic lupus erythematosus is an autoimmune disease, in which the patient develops antibodies that react with many tissues of his own body. Dominant antibodies are directed against components of the cell nucleus, with epitopes that may be found in DNA, and in proteins that constitute small ribonucleoprotein particles (snRNPs). The first laboratory test ever devised for this disease was the LE (lupus erythematosus) cell test. This test has to be repeated many times, before it results in a positive reaction in about 90% of the people with systemic lupus erythematosus. Also, the LE cell test is not specific for lupus, and can be positive in up to 20% of the people with rheumatoid arthritis, in some patients with other rheumatic conditions like Sjogren's syndrome or scleroderma, in patients with liver disease, and in persons taking drugs such as hydralazine and procainamide. The ANA test, which detects antibodies against nuclear antigens, is more specific for lupus than the LE test, and is positive in many patients that suffer from systemic lupus erythematosus. As with the LE test, a positive ANA is not diagnostic for lupus since the test may also be positive in people with scieroderma, dermatomyositis, rheumatoid arthritis, Sjogren's syndrome, in patients treated with certain drugs, or in patients suffering from infectious mononucleosis, liver disease, malaria etc. For these reasons and because the summed tests are expensive, new tests have been developed which are very helpful in the diagnosis of SLE. These include the anti-DNA antibody test, the anti-Sm antibody test, the anti-RNP antibody test, the anti-Ro antibody test, and tests which measure serum complement levels. Often, correct diagnosis will depend on the interpretation of many separate tests and symptoms. Web site: http://www.delphion.com/details?pn=US06362007__ •
Monoclonal antibodies reactive with shared idiotypes on human antibodies to native DNA from patients with systemic lupus erythematosus Inventor(s): Diamond; Betty A. (New York, NY) Assignee(s): Yeshiva University (Bronx, NY) Patent Number: 4,692,416 Date filed: November 16, 1983 Abstract: The invention relates to monoclonal anti-idiotypic antibodies to human antiDNA antibodies. Monoclonal, anti-idiotypic antibodies are produced using hybridoma technology. The antibodies are used as diagnostic reagents in methods to determine the presence of anti-native DNA antibodies in serum from patients suspected of having systemic lupus erythematosus. Excerpt(s): The present invention relates to monoclonal antibodies capable of reacting with shared idiotypes on human anti-native DNA antibodies. The invention also relates
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to diagnostic test methods to detect the presence of anti-native DNA antibodies in patients suspected of having systemic lupus erythematosus. The term "antibody" as used in immunology is a generic term and is used to cover numerous immunoglobulin molecules which may be alike in some respects and different in other respects. Antibodies sharing a common effector function are referred to as isotypes and include the major immunoglobulin classes IgA, IgD, IgE, IgG and IgM, each of which is constructed from a heavy polypeptide chain characteristic of the particular class and a light polypeptide chain (either kappa or lambda), the heavy and light chains being joined by disulfide bridges. Heterologous antibodies, i.e. those raised in one species against the antibodies of another species, are useful in recognizing isotypes. Antibodies of a given isotype, e.g., IgG, can be subdivided further on the basis of the particular type of heavy chain from which they are composed, e.g.gamma.1,.gamma.2,.gamma.3, etc. Antibodies having the same general type of heavy chain can still show some heterogeneity in the heavy chain. Within a given animal species, certain regions on the heavy chain of a given isotype may be the same or different. Those antibodies showing similarity within these regions are referred to as allotypes. The similarity is believed to be of genetic origin. Web site: http://www.delphion.com/details?pn=US04692416__ •
Nucleolus autoantigenic marker for systemic lupus erthyematosus Inventor(s): Rattner; Jerome Bernard (35 Point McKay Court, Calgary, Alberta, CA), Whitehead; Clark (1894 20thSt. NW., Rochester, MN 55901) Assignee(s): none reported Patent Number: 6,177,254 Date filed: December 15, 1998 Abstract: A novel nucleolus protein has been identified and cloned using human autoimmune serum. Its cDNA and amino acid sequences have been determined and are disclosed. This antigenic protein, termed ASE-1, has an approximate molecular mass of 55 kDa. Immunoblot analysis indicates that both the native protein and the in vitro translation products of the cDNA migrate on SDS-PAGE at an apparent molecular mass of 90 kDa. Indirect immunofluorescence analysis using antibodies generated to cloned regions of ASE-1 indicates that this protein occurs at the fibrillar centers of the nucleolus in the putative sites of rDNA transcription. During cell division ASE-1 localizes to the nucleolus organizer regions of the chromosomes, where it is closely associated with RNA polymerase 1. As an autoantigenic nucleolar protein, ASE-1 has been found to be a reliable serum marker for systemic lupus erthyematosus (SLE). This finding makes ASE1 useful in the clinical detection and characterization of the disease. To identify the presence of SLE in an individual patient, a serum samples is taken and screened against the cloned ASE-1 protein to identify sera with anti-ASE-1 autoantibodies. This screening can be done using an ELISA assay, western blot techniques, or by binding the antigen to microspheres and identifying reactive sera by flow cytometry. Excerpt(s): The invention pertains to the discovery of a novel human autoantigen. More particularly, the autoantigen discovered has been sequenced and is useful in the identification of individuals with systemic lupus erthyematosus. Systemic lupus erythematosus (SLE), commonly known as Lupus, is an autoimmune disease characterized by dysregulation of the immune system resulting in the production of antinuclear antibodies, the generation of circulating immune complexes, and the activation of the complement system. The immune complexes build up in the tissues
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and joints causing inflammation, and degradation to both joints and tissues. While the word "systemic" correctly suggests that the disease effects the entire body and most organ systems, the disease most often involves inflammation and consequent injury to the joints, skin, kidney, brain, the membranes in body cavities, lung, heart, and gastrointestinal tract. An individual with SLE often experiences unpredictable acute episodes or "outbreaks" and equally unexpected remissions. The pathologic hallmark of the disease is recurrent, widespread, and diverse vascular lesions resembling a rash or changes on the surface of the skin. Physicians have known Lupus since 1828 when it was first described by the French dermatologist, Biett. Early studies were simply descriptions of the disease, with emphasis on the skin rashes typically present in those afflicted with the disease as well as other easily visible symptoms. Forty-five years later a dermatologist named Kaposi noted that some patients with lupus erythematosus (LE) skin lesions showed signs of affected internal organs. In the 1890s, Sir William Osler, a Canadian physician, observed that SLE could affect internal organs without the occurrence of skin changes. In 1948, Dr. Malcolm Hargraves of the Mayo Clinic isolated and described the particular morphology of the LE cell. This cell was found in the blood of patients with SLE. Hargraves' discovery has enabled physicians to identify many more cases of SLE by using a simple blood test. As a result, the number of SLE cases diagnosed has steadily risen. Web site: http://www.delphion.com/details?pn=US06177254__ •
Peptides for the production of preparations for the diagnosis and therapy of systemic lupus Inventor(s): Zeppezauer; Michael (Scheidt, DE), Schonberger; Arno (Hamburg, DE), Cebecauer; Ladislav (Piestany, CS) Assignee(s): Symbiotec Gesellschaft zur Erforschung und Entwicklung auf dem Gebiet der (Herborn, DE) Patent Number: 6,369,203 Date filed: September 16, 1992 Abstract: Peptides are proposed with antigenic or immunogenic determinants, which result from autoantibodies in the body fluids of patients, who are suffering from systemic lupus erythematosus (SLE). In the case of the peptides it is preferably a question of the C terminus of H1 with the sequence section 187-211 and the N termini of H2B with the sequence sections 1-35 and 36-76, which are capable of cross reactions with the autoantibodies (anti-histone-antibodies). The invention furthermore provides ways of forming monoclonal antibodies and antiidiotypical antibodies, which are directed against autoantibodies. The diagnosis of SLE is possible in accordance with the invention with a high degree of certainty and the monoclonal antibodies directed against the autoantibodies are suitable for the production of medicaments for the therapy of SLE. Excerpt(s): The present invention relates to peptides with antigenic or immunogenic determinants, which may be recognized by autoantibodies in the body fluids of patients, who are suffering from systemic lupus erythematosus (SLE). Diseases of the "rheumatic group" are characterized by a large number of clinical phenomena and by a wide spectrum of autoantibodies. The latter are directed against various different components of normal cells. The said diseases include systemic lupus erythematosus (SLE) which may occur spontaneously or may be induced by medicaments. In the case of SLE the occurrence of autoantibodies is particularly frequent, which are directed against
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components of the cell nucleus (antinuclear antibodies, ANA's), these including inter alia double strand desoxyribonucleic acid (DS-DNA) and histone proteins, ribonucleic acid (RNA), complexes of DNA and histones as well as enzymes. Histones consist of a number of classes of proteins, the so-called core histones H1A, H2B, H3 and H4, which are found in the nucleosomes, and the linker histones H1 and H5, to which linking functions are attributed in the formation of chromatin. Many attempts have been made to correlate the frequency of autoantibodies, which are directed against special antigens, with certain rheumatic syndromes. It has been discovered that in the case a patient with SLE autoantibodies against histones (AHA's, anti-histone autoantibodies) occur more frequently. Normally the "enzyme linked immuno-sorbent assay" (ELISA) is utilized for determination, in the case of which the sera of patients and of healthy control subjects are tested on purified cell components (i. e. antigens). Pure histone is inter alia employed as an antigen for the testing of SLE sera. Web site: http://www.delphion.com/details?pn=US06369203__ •
Peptides for the treatment of systemic lupus erythematosus Inventor(s): Naparstek; Yaakov (Jerusalem, IL) Assignee(s): Hadasit Medical Research Services & Development Company Ltd. (Jerusalem, IL) Patent Number: 6,228,363 Date filed: September 20, 1999 Abstract: A method is disclosed for treating systemic lupus erythematosus in a mammalian subject, comprising administering to said subject an effective dose of at least one laminin peptide, or an analog or a derivative thereof. In one exemplary embodiment, the laminin peptide is selected from the group consisting of R38, and claimed R38 analogs and derivatives thereof including 5200, 5104, 5105, 5106, 5107, 5108, 5109, and 5110. The laminin peptides of the present invention may be prepared by known chemical synthetic methods or by biotechnological methods. Assays useful for the diagnosis of and following pathological activity course of systemic lupus erythematosus in patients suffering therefrom. Excerpt(s): This invention relates to the use of laminin peptides and laminin derivatives, including R38 peptide and related analogs for the treatment and detection of systemic lupus erythematosus. Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs. Through the involvement of the kidneys in the autoimmune inflammatory process lupus glomerulonephritis is a major cause of morbidity and mortality in this disease (Alarcon-Segovia D. In: Primer on the Rheumatic diseases. Ed. Schumascher H. R. Arthritis Foundation, Atlanta, Ga., (1988) pp. 96-100). Serologically, the disease is characterized by the occurrence of a variety of autoantibodies in the serum, of which the most prominent are the anti-DNA auto antibodies (Naparstek Y et al Annu. Rev. Immunol. (1993) 11 79-104). Although low titers of anti-DNA antibodies may occur in various inflammatory and autoimmune diseases, high levels are found mainly in SLE, and the combination of high anti-DNA antibodies with low complement levels is virtually diagnostic of SLE (Wallace D. J. et al In: Dubois' Lupus erythematosus. Lea and Febiger, Philadelphia, 1993). Web site: http://www.delphion.com/details?pn=US06228363__
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Peptides of the antigen Sm-D and their use, in particular for the diagnostics of systemic lupus erythematosus (SLE) Inventor(s): Marell; Jeannette (Berlin, DE), Burmester; Gerd-Rudiger (Berlin, DE), Riemekasten; Gabriele (Berlin, DE), Hiepe; Falk (Berlin, DE) Assignee(s): Imtec Immundiagnostika GmbH () Patent Number: 5,945,105 Date filed: October 18, 1996 Abstract: Peptides of the antigen Sm-D and their use, in particular for the diagnostics of the SLE. The invention relates to peptides of the antigen Sm-D, comprised of 35 to 45 amino acids, which form a conformation epitope and which are capable of binding autoantibodies, such as they occur in connection with systemic lupus erythematosus (SLE). Particularly preferred is the peptide of 37 amino acids with the structure VEPKVKSKKREAVAGRGRGRGRGRGRGRGRGRGGPRR (SEQ ID NO:3) and its mutants and variants, respectively. Excerpt(s): The invention relates to the peptides of the antigen Sm-D, which are recognized by antibodies in biological fluids, in particular of antibodies which are present in the body fluids of patients which suffer from systemic lupus erythematosus (SLE). Furthermore, the invention relates to the use of these peptides and their sequential products for the diagnostics of SLE in vitro, as well as their use as a vaccine for the generation of tolerance mechanisms and for the preparation of immunogenic and antigenic compositions and of test kits. In addition, the invention concerns antibodies which are induced in vivo by these peptides as well as a method for the determination of anti-Sm-D antibodies in biological fluids. Web site: http://www.delphion.com/details?pn=US05945105__
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Peptides of the SM-D antigen and their use for diagnosis of systemic lupus erythematosus Inventor(s): Barakat; Samira (Strasbourg, FR), Weber; Jean-Christophe (Strasbourg, FR), Muller; Sylviane (Strasbourg, FR), Briand; Jean-Paul (Strasbourg, FR), van Regenmortel; Marc (Strasbourg, FR) Assignee(s): Pasteur Sanofi Diagnostics (Marnes la Coquette, FR) Patent Number: 5,407,833 Date filed: April 3, 1992 Abstract: Peptides comprising between 20 and 39 amino acids capable of reacting with antibodies against the Sm-D polypeptide. These peptides may be used in a diagnostic method to detect of antibodies against the Sm-D polypeptide in a biological sample from a person suffering from systemic lupus erythematosus. Excerpt(s): The present invention concerns peptides capable of being recognized by antibodies present in biological fluids, in particular sera of patients or animals stricken with systemic lupus erythematosus (DLE). The invention also concerns applications of these peptides, and compositions which contain them, to the in vitro diagnosis of systemic lupus erythematosus in humans, as well as their use in the composition of diagnostic kits. The invention further concerns applications of these peptides in the production of immunogenic compositions and vaccination compositions against this disease.
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Snake venom lupus anticoagulant protein Inventor(s): Lian; Eric Chun-Yet (Coral Gables, FL) Assignee(s): Eric Chun-Tet Lian (Coral Gables, FL) Patent Number: 5,763,403 Date filed: October 31, 1995 Abstract: A lupus anticoagulant like protein obtained from Agkistrodon halys brevicaudus venom, methods and tests for detecting the presence of lupus anticoagulant in blood and methods of treating antiphospholipid syndrome and thrombotic disorders using the protein are disclosed. Excerpt(s): This invention relates to a lupus anticoagulant like protein, particularly a lupus anticoagulant like protein from Agkistrodon halys brevicaudus venom, to methods and tests for detecting the presence of lupus anticoagulant and methods of treating antiphospholipid syndrome and thrombosis using the protein. Lupus anticoagulants (LA) are immunoglobulins that interfere with blood coagulation. Lupus anticoagulants are found in the blood of many people. This includes healthy people and those not suffering from lupus erythematosus. They may also be found in people having other immune system disorders such as viral infections including AIDS, tumors such as lymphoma and prostatic carcinoma, rheumatoid arthritis and the like. Such persons having lupus anticoagulants in their blood system may or may not display symptoms. However, they may suffer from disorders such as antiphospholipid syndrome, thrombosis, spontaneous abortion, thrombocytopenia, pulmonary hypertension and the like. Accordingly, there is a great need to accurately determine the presence of lupus anticoagulants in the blood stream and develop methods of treating adverse consequences of the presence of lupus anticoagulants, such as antiphospholipid syndrome, thrombotic disorders such as venous thrombosis, coronary arterial disease such as myocardial infarction (MI), cerebral vascular disease such as stroke, peripheral arterial disease, disseminated intravascular coagulation (DIC) and the like. Not only has it been a longstanding problem in the art to provide a reliable and consistent means for testing for the presence of lupus anticoagulants, it has further been a longstanding problem to provide effective methods of treatment of adverse symptoms exhibited in the presence of lupus anticoagulants, such as antiphospholipid syndrome, thrombosis and the like. These maladies can be highly dangerous to humans and can result in death. It is therefore quite important that treatments overcome such potentially fatal afflictions. Web site: http://www.delphion.com/details?pn=US05763403__
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Synthetic peptides and pharmaceutical compositions comprising them for the treatment of systemic lupus erythematosus Inventor(s): Waisman; Ari (Tel-Aviv, IL), Mozes; Edna (Rehovot, IL) Assignee(s): Yeda Research and Development Co. Ltd. (Rehovot, IL) Patent Number: 6,613,536 Date filed: September 29, 1997
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Abstract: Synthetic peptides based on a complementarity-determining region (CDR) of the heavy or light chain of a pathogenic anti-DNA monoclonal antibody that induces a systemic lupus erythematosus (SLE)-like disease in mice, and analogs, and salts and chemical derivatives thereof; dual peptides comprising two such peptides or analogs covalently linked to one another either directly or through a short linking chain; peptide polymers comprising a plurality of sequences of said peptide or analog thereof; and peptide polymers attached to a macromolecular carrier, are disclosed, and pharmaceutical compositions comprising them for the treatment of SLE in humans. Excerpt(s): This application is a 371 national stage application of PCT/US96/04206, filed Mar. 27, 1996, which claims the benefit of priority to Israel Application No. 113,159, filed Mar. 28, 1995. The present invention relates to synthetic peptides and to pharmaceutical compositions comprising them useful for the treatment of systemic lupus erythematosus (SLE) in humans. Autoimmune diseases are characterized by immune responses that are directed against self antigens. These responses are maintained by the persistent activation of self-reactive T lymphocytes. T lymphocytes are specifically activated upon recognition of foreign and/or self antigens as a complex with self major histocompatibility complex (MHC) gene pro(ducts on the surface of antigen-presenting cells (APC). Web site: http://www.delphion.com/details?pn=US06613536__ •
Test for lupus anticoagulant Inventor(s): Stocker; Kurt (Aesch, CH), Triplett; Douglas A. (South Muncie, IN) Assignee(s): Pentapharm AG (Basel, CH) Patent Number: 5,705,198 Date filed: June 6, 1995 Abstract: It was found that the use of a phospholipid dependent prothrombin activator purified from the venom of snakes belonging to the Elapidae family, especially members of the Oxyaranus and Psuedonaja genera is most useful in tests for the determination of Lupus Anticoagulant. Based on this, several clotting, chromogenic aria immunochromogenic tests have been developped. Excerpt(s): The present invention relates to a phospholipid dependent prothrombin activator, to a method for its purification, and to a test for the detection of Lupus Anticoagulant using the activator. The lupus anticoagulant (LA) is an immunoglobulin (IgG, IgM, or a mixture of both) which interferes with one or more of the in vitro phospholipid dependent tests of coagulation (activated partial thromboplastin time ›APTT!; prothrombin time ›PT!; dilute Russell Viper Venom Time ›dRVVT!). In contrast to specific inhibitors of coagulation proteins, LA has no reactivity with any of the individual Coagulation factors. The name is a misnomer since the vast majority of patients do not have underlying systemic lupus erythematosus (SLE). More commonly, LA is secondary to infections, drugs (e.g. chlorpromazine, quinidine, procainamide) or it may be seen in an autoimmune disease which has recently been described: Primary Antiphospholipid Antibody Syndrome. Paradoxically, LA is not associated with clinical bleeding unless there is some associated hemostatic defect (e.g. thrombocytopenia). Approximately 30 to 40% of patients with LA have a history of venous and arterial thromboembolic events. For a number of years, there has been much discussion as to whether LA was causative, a consequence, or coincident with thrombosis. More recent work in animal models would suggest that indeed LA is a cause of a thrombotic
Patents 333
predisposition. Other clinical-manifestations of LA include recurrent fetal loss, intrauterine fetal growth retardation, and prematurity. Also, LA may be associated with thrombocytopenia or autoimmune hemolytic anemias. Two recent excellent reviews discuss LA and its closely related antibody: anticardiolipin antibodies ›Tripleft D. A., Brandt J. T., Lupus Anticoagulants: Misnomer, Paradox, Riddle Epiphenomenon. Hematol. Pathol. 2, 121-143, 1988; Love P. E., Santoro S. A., Antiphospholipid Antibodies: Anticardiolipin and the Lupus Anticoagulant in Systemic Lupus Erythematosus (SLE) and Non-SLE Disorders. Ann. Int. Med. 112, 682-698, 1990!. Web site: http://www.delphion.com/details?pn=US05705198__ •
Treatment for systemic lupus erythematosus Inventor(s): Richardson; Bruce C. (3400 West Bayshore Rd., Palo Alto, CA 94303) Assignee(s): none reported Patent Number: 5,679,651 Date filed: June 5, 1995 Abstract: Cytarabine (ara-C) is effective in the treatment of systemic lupus erythematosus. Excerpt(s): The present invention relates to the treatment of disease, particularly to systemic lupus erythematosus, and specifically to a new use of the compound ara-C in the treatment thereof. As discussed in the Primer on Rheumatic Diseases, Tenth Edition, ›Schumacher, et al., Eds., (The Arthritis Foundation, Atlanta, Ga.), Chapter 11, pp. 100116 (1993)! systemic lupus erythematosus "SLE") is an idiopathic disease characterized by antibodies (autoantibodies) against a wide range of autoantigens in the nucleus and cytoplasm of cells, and a constellation of pathologic abnormalities involving the kidney, skin, brain, lungs and other organs. Autoantibodies to double-stranded DNA and an RNA-protein complex termed Sm are found essentially only in SLE patients and are included as serologic criteria in the classification of SLE. SLE is primarily a disease of young women, ages 15 to 40; it affects about 1 in 2,000 individuals and shows a strong familial aggregation. While genetically determined immune abnormalities are implicated in the cause of SLE, the triggering event is suggested to include both exogenous and endogenous factors, likely to be mutagenic in origin. The pathologic findings of SLE are manifested by inflammation, blood vessel abnormalities encompassing both bland vasculopathy and vasculitis, and immune complex deposition. Although the cause of SLE remains unknown, certain environmental and pharmacologic agents, including UV light and drugs such as procainamide and hydralazine have been shown to trigger a lupus-like illness in genetically predisposed individuals. Yung, et al., Rheum. Dis. Clin. North Am., 20:61 (1994) and Decker, et al., Ann. Intern. Med., 91:587 (1979). Autoreactivity induction by inhibition of T cell DNA methylation, e.g., using the drug 5-aza-cytidine ("5-aza-C") has also been shown to cause a lupus-like disease in syngenic recipients. Quddus, et al., J. Clin. Invest. 92:38 (1993). This has been extended to a murine model involving the adoptive transfer of CD4.sup.+ T cells treated with the DNA methylation inhibitors. Yung, et al., J. Immunol., 154:30253035 (1995). Web site: http://www.delphion.com/details?pn=US05679651__
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Treatment of human plasma with brown recluse spider toxin to emulate a lupus anticoagulant Inventor(s): McGlasson; David L. (San Antonio, TX), Babcock; James L. (San Antonio, TX) Assignee(s): The United States of America as represented by the Secretary of the Air (Washington, DC) Patent Number: 4,877,741 Date filed: October 24, 1988 Abstract: A new method for improving the accuracy of blood tests for the presence of lupus anticoagulants and for blood factor deficiencies is disclosed. Brown recluse spiders are collected, their venon glands removed by microdissection and the active toxin extracted. The toxin is mixed with normal donor plasma in concentrations of about 3.5.mu.l/ml of toxin to plasma. The treated plasma successfully mimics human plasma having lupus anticoagulants. By using the treated plasma in blood tests and assays as a standardized control to which the results from tests on questioned blood plasma samples may be compared, the equipment and procedures for those tests may be calibrated and test results made more sensitive and reliable. Excerpt(s): The present invention relates generally to medical testing methods, and more specifically to the use of a brown recluse spider (Loxosceles reclusa) toxin treated human plasma as a positive control, or standardized reference, for lupus anticoagulant blood tests. Lupus anticoagulants are antibodies that interfere with blood coagulation, or clotting. Curiously, they are anticoagulants only in vitro, or outside the human body. In vivo, or inside the body, they act to increase the risk of thrombosis, or detrimental blood coagulation inside the heart, arteries, veins or capillaries. Lupus anticoagulants are found in the blood of many persons, and not merely in the blood of persons suffering from systemic lupus erythematosus, an inflammatory autoimmune disorder from which lupus anticoagulants derive their name. While persons having lupus anticoagulants present in their blood often show no adverse symptoms, a significant percentage of such persons will suffer from such complications as thrombosis, seizure disorders and, in women, spontaneous abortions. Unfortunately, testing blood for the presence of lupus anticoagulants is very inexact. Present tests or assays used for detecting lupus anticoagulants, which generally test in vitro for various impaired coagulation indicators, can give misleading results from, for example, the presence of mild blood factor deficiencies. Blood factors are contributors to beneficial blood clotting and a deficiency in any one of many such factors will reduce clotting both in vivo and in in vitro tests so that they can produce, in vitro, the same test results as lupus anticoagulants. Vice versa, a mild blood factor deficiency may be misdiagnosed as the presence of a mild lupus anticoagulant. To most accurately test blood plasma samples for lupus anticoagulants, a standardized positive control is required for calibration and comparison of both testing equipment and technique. Because blood plasma with a lupus anticoagulant is not easily stored, and because patients with a lupus anticoagulant for obtaining blood samples are not always convenient, there is a need for a commercially available control plasma that accurately mimics the effects of a lupus anticoagulant in human plasma for laboratory testing. Without such a positive control, laboratory technicians cannot be certain that their testing for the presence of lupus anticoagulants is indeed performed in a manner consistent with expected results. Web site: http://www.delphion.com/details?pn=US04877741__
Patents 335
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Treatment of lupus erythematosus Inventor(s): Lezdey; Darren (Indian Rocks Beach, FL), Lezdey; Jarett (Indian Rocks Beach, FL) Assignee(s): Alphamed Pharmaceuticals Corp (Clearwater, FL) Patent Number: 6,537,968 Date filed: July 24, 2000 Abstract: The present invention provides for the treatment of an individual suffering from lupus erythematosus utilizing a serine protease inhibitor. The treatment includes the use of a corticosteroid that is administered separately or in combination. The serine proteases preferred are alpha 1-antitrypsin, secretory leucocyte protease inhibitor, alpha 2-macroglobulin or mixtures thereof. Excerpt(s): The present invention relates to the treatment of lupus erythematosus. More specifically, there is provided the treatment of inflammatory conditions, rashes or lesions which occur with patients with systemic lupus erythematosus (SLE) by the administration of protease inhibitors. The common treatment for lupus erythematosus involves the H use of several drugs as well as sunscreens. Hydroxychloroquine alone or in combinations with oral steroids is used. Topical steroids and/or vitamin A are also used for treating skin eruptions. The patients with severe SLE involving several organs have been treated with immunosuppressive agents (corticosteroids and pulse cyclophosphamide therapy). The treatments have not been effective in many cases and have resulted in other problems resulting from an overuse of steroids. In many cases, the presence of the skin lesions results in keloid scarring. The use of steroids not only does not prevent the scarring but can lead to thinning of the skin so as to lead to further lesions. Web site: http://www.delphion.com/details?pn=US06537968__
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Treatment of systemic lupus erythematosus with dehydroepiandrosterone Inventor(s): McGuire, deceased; James L. (late of Stanford, CA), Engleman; Edgar G. (Stanford, CA), Van Vollenhoven; Ronald F. (Stanford, CA), McGuire, administratrix; Linda R. (Westboro, MA) Assignee(s): The Board of Trustees of the Leland Stanford Junior University (Stanford, CA) Patent Number: 5,817,650 Date filed: April 4, 1997 Abstract: Systemic lupus erythematosus (SLE) is treated with dehydroepiandrosterone or its metabolite, sulfate ester, by itself or in combination with other therapies. Substantial improvement in SLE patients is observed during the course of treatment. Excerpt(s): The field of this invention concerns the treatment of systemic lupus erythematosus. Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease. Patients with SLE manifest various immunological abnormalities which probably reflect the immunopathological processes occurring concurrently in this multisystem disease. One consistent finding appears to be defective IL-2 production by peripheral blood T-lymphocytes which is independent of age or overall disease activity (Alcocer-Varela and Alarcon-Segovia, J. Clin. Invest. (1982), 69, 1388; Linker-Israeli, et al., J. Immunol. (1983), 130, 2651; Murakawy, et al., ibid (1985), 134, 187). The precise
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pathological significance of this is unknown. The administration of IL-2 in the murine lupus-like model MRL/lpr attenuated the autoimmune disease (Gutierrez-Ramos, Nature (1990), 346, 27). The sex hormone status of patients with SLE suggests that there is a relative deficiency of androgens (Jungers, et al. Arthritis Rheum. (1982), 25, 454; Lahita, et al. ibid (1983), 26, 1517). The administration of the androgen Danazol to patients with SLE, based on the proposition that there may be a protective effect conferred by androgens, has produced variable benefits with respect to disease activity and autoantibody production (Steinberg, et al., Arthritis Rheum. (1979), 22, 1170; Roubinian, et al., ibid (1979), 22, 1399). Dehydroepiandrosterone (DHEA) is a natural androgen that is an intermediate in the synthetic pathway of cholesterol to testosterone and it is the most abundant secretory product of human adrenal glands (Vande Wiele, et al. Recent Prog. Horm. Res. (1963), 19, 275). About 30 mg/day of DHEA is produced by the adrenal glands in the form of the inactive sulfate ester and DHEA serum levels show a striking age-related decline (Barrett-Connor, et al. New Engl. J. Med. (1986), 315, 1519). DHEA has up-regulatory effects on IL-2 production by stimulating human T-cells in vitro. In the NZB/W mouse DHEA was found to profoundly delay the appearance of anti-DNA antibodies as well as the onset of nephritis and to prolong life (Lucas, et al. J. Clin. Invest. (1985), 75, 2091). There have also been reports that the administration of DHEA to MRL/lpr mice with severe lupus-like disease resulted in dramatic reversal of disease activity. Web site: http://www.delphion.com/details?pn=US05817650__ •
Use of.DELTA.5-androstene-3.beta.ol-7,17-dione erythematosus
in
the
treatment
of
lupus
Inventor(s): Weeks; Charles E. (1235 Jensen Park Dr., New Albany, OH 43054), Lardy; Henry A. (1829 Thorstrand Rd., Madison, WI 53705) Assignee(s): none reported Patent Number: 6,593,316 Date filed: March 22, 2002 Abstract: Lupus erythematosus can be treated by administering therapeutic amounts of.DELTA.5-androstene-3.beta.-ol-7,17-dione and metabolizable precursors thereof, such as.DELTA.5-androstene-3.beta.-acetoxy-7,17-dione, which are readily metabolized in vivo to.DELTA.5-androstene-3.beta.-ol-7,17-dione but are not appreciably metabolizable in vivo to androgens, estrogens or dehydroepiandrosterone. Such treatment can be prophylactic, ameliorative or curative in nature. Excerpt(s): This invention broadly relates to treatment strategies for lupus erythematosus. More specifically, the invention relates to prophylactic, ameliorative and curative drug therapies for lupus erythematosus. Lupus erythematosus is an autoimmune disorder which may, but does not always, affect many different organ systems in an affected individual. Lupus erythematosus (hereinafter "lupus") may affect the heart, lungs, skin, joints, kidneys, nervous system, lymph gland system, blood cells and/or blood vessels. Certain forms of lupus affect only or predominantly the skin. These forms of lupus are the most visible manifestations of the disease. The immune system of the body is a complex and elaborate mechanism of protection from foreign substances. The immune system provides resistance to foreign cells and substances (e.g., bacteria or virus) that may cause injury, as well as searching out abnormal cells (e.g., cancerous cells) within the body for destruction. The invading or abnormal cells are neutralized by the immune system humoral and cellular components, including
Patents 337
lymphocytes, antibodies, mediating (regulating such as Lymphokines) systems, and effector (cytotoxic) cells. As an example. the immune system can recognize the invading or abnormal cells (antigens) within the body and produce antibodies (proteins) which attach to the recognized antigens, leading to their removal. Autoimmunity occurs when the immune system produces antibodies to normal cells in the body. This produces inflammation of normal tissue, resulting in damage and loss of function. In other instances, antibodies attach to antigens within the blood plasma to form immune complexes that may be deposited in normal tissue resulting in inflammation and damage. Web site: http://www.delphion.com/details?pn=US06593316__ •
Use of a peptide compound in the treatment of systemic lupus erythematosus Inventor(s): Fassina; Giorgio (Milan, IT), Rossi; Maria (Portici, IT), Marino; Maria (Caserta, IT) Assignee(s): Tecnogen S.C.p.A. (Piana di Monte Verna, IT) Patent Number: 6,303,577 Date filed: May 4, 1999 Abstract: Use of a peptide compound of formula(H.sub.2 N-X.sub.1 -Thr-X.sub.2 CO).sub.n -R (I)whereinX.sub.1, X.sub.2, n and R have the meanings stated in the description for preparing a pharmaceutical composition useful in the treatment of Systemic Lupus Erythematosus. Excerpt(s): This application is based on European Patent Application No. 98830310.3 filed on May 21, 1998, the content of which is incorporated hereinto by reference. This invention relates to the use of a peptide compound for preparing a pharmaceutical composition useful in the treatment of Systemic Lupus Erythematosus as well as a method of treating a patient suffering from Systemic Lupus Erythematosus. R, when n is 2, 3 or 4 is a group suitable for forming a dimer, trimer or tetramer, while, when n is 1, R is OH, a single amino acid residue, or a peptide chain comprising up to 7 amino acid residues, useful as a ligand of immunoglobulins. Web site: http://www.delphion.com/details?pn=US06303577__
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Use of annexins as a lupus anticoagulant control or standard in clotting tests Inventor(s): Kraus; Michael (Marburg, DE) Assignee(s): Dade Behring Marburg GmbH (Marburg, DE) Patent Number: 6,194,214 Date filed: August 10, 1998 Abstract: The invention relates to a process for the production of plasmas with added annexins for use as a control or standard in all functional clotting tests which are used for the detection of a lupus anticoagulant. Excerpt(s): The invention relates to a process for the production of plasmas for use as a control or standard in all functional clotting tests which are used for the detection of a lupus anticoagulant. Lupus anticoagulants are immunoglobulins and belong to the acquired autoantibodies type. They are directed against phospholipids or
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phospholipid/protein complexes and prolong the clotting time in customary diagnostic clotting tests (see Triplett D., et al. Hematologic Pathology 1988; 2: 121-143). These immunoglobulins are to be differentiated from other autoantibodies likewise against lipids, in particular cardiolipins. Both groups are clinically assigned to the antiphospholipid syndrome (APS) which manifests itself in thromboses and an increase in birth complications (miscarriages). The pathological mechanism of the lupus anticoagulants is still unclarified for several reasons. Firstly, the specificity of the occurring antibodies and thus the mechanism of action is individually different from patient to patient. Secondly, the subclasses of the immunoglobulins (IgM, IgG, IgA) and the antibody titers vary. Thirdly, there is a paradox between the determination of the lupus anticoagulant and clinical manifestation: a prolongation of the clotting time in in vitro tests, as is caused by lupus anticoagulant, points to an increased proneness to bleeding, in vivo, however, it is manifested in an increased proneness to thromboses. The diagnosis of a lupus anticoagulant is therefore restricted to a phenomenological, description of the behavior of a plasma sample in various clotting tests according to the recommendations of international committees (Brandt, J. T. et al., Thrombosis Haemostasis 1995; 74: 1185-1190). These tests are the activated partial thromboplastin time (APTT), the kaolin clotting time (KCT) the dilute thromboplastin time (dPT) and the Russell's viper venom time (RVVT). A prolongation of the clotting time in these tests, however, is also obtained by a factor deficiency, which is why in the so-called plasma exchange test the pathological sample is mixed with normal plasma and as a rule determined in the APTT. A factor deficiency, as a rule, is already compensated for in a substitution of 50% by mixing with the normal plasma, while in the presence of a lupus anticoagulant pathological results are still obtained. Furthermore, the phospholipid dependence is to be checked, which is carried out using the same reagents, but with different concentrations of phospholipids. Furthermore to be differentiated are autoantibodies against individual clotting factors, which are likewise not compensated for by 1+1 mixing with a normal plasma. As a rule, these factor antibodies, however, only act in one of the two pathways of the clotting system (in particular so-called Factor VIII inhibitors) and are recognized by the comparison of the various pathways, i.e. by the comparison of the abovementioned tests (APTT for the intrinsic, PT for the extrinsic pathway). Web site: http://www.delphion.com/details?pn=US06194214__ •
Use of delta5-androstene-3beta-ol-7, 17-dione in the treatment of lupus erythematosus Inventor(s): Lardy; Henry A. (Madison, WI), Weeks; Charles E. (Battle Creek, MI) Assignee(s): Humanetics Corporation (Chanhassen, MN) Patent Number: 6,372,732 Date filed: December 4, 2000 Abstract: Lupus erythematosus can be treated by administering therapeutic amounts of delta-5-androstene-3-beta-ol-7,17-dione and its metabolizable precursors, which are not appreciably metabolized in vivo to androgens, estrogens or dehydroepiandrosterone. Such treatment can be prophylactic, ameliorative or curative in nature. Excerpt(s): This invention broadly relates to treatment strategies for lupus erythematosus. More specifically, the invention relates to prophylactic, ameliorative and curative drug therapies for lupus erythematosus. Lupus erythematosus is an autoimmune disorder which may, but does not always, affect many different organ systems in an affected individual. Lupus erythematosus (hereinafter "lupus") may affect
Patents 339
the heart, lungs, skin, joints, kidneys, nervous system, lymph gland system, blood cells and/or blood vessels. Certain forms of lupus affect only or predominantly the skin. These forms of lupus are the most visible manifestations of the disease. The immune system of the body is a complex and elaborate mechanism of protection from foreign substances. The immune system provides resistance to foreign cells and substances (e.g., bacteria or virus) that may cause injury, as well as searching out abnormal cells (e.g., cancerous cells) within the body for destruction. The invading or abnormal cells are neutralized by the immune system humoral and cellular components including lymphocytes, antibodies, mediating (regulating such as lymphokines) systems, and effector (cytotoxic) cells. As an example. the immune system can recognize the invading or abnormal cells (antigens) within the body and produce antibodies (proteins) which attach to the recognized antigens, leading to their removal. Autoimmunity occurs when the immune system produces antibodies to normal cells in the body. This produces inflammation of normal tissue, resulting in damage and loss of function. In other instances, antibodies attach to antigens within the blood plasma to form immune complexes that may be deposited in normal tissue resulting in inflammation and damage. Web site: http://www.delphion.com/details?pn=US06372732__
Patent Applications on Lupus As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to lupus: •
Antigen to systemic lupus erythematosis and diagnostic assay Inventor(s): Yoo, Tai June; (Memphis, TN) Correspondence: JOHN S. PRATT, ESQ; KILPATRICK STOCKTON, LLP; 1100 PEACHTREE STREET; SUITE 2800; ATLANTA; GA; 30309; US Patent Application Number: 20020192723 Date filed: February 25, 2000 Abstract: A 28 kD antigen present in the intracellular signal transduction oncogene and an immunoassay method for diagnosing Systemic Lupus Erythematosis using the 28 kD antigen as a target substance for detecting target binding substance in biological fluid from an animal or human having symptoms of Systemic Lupus Erythematosis. Excerpt(s): This application claims the benefit of co-pending U.S. provisional patent application Ser. No. 60/121,548, filed Feb. 25, 1999, which is incorporated by reference in its entirety herein. In a prior study on Systemic Lupus Erythematosis and Autoantigen, Yoo et al. found that these patients have auto-antibody to c-raf protein. It was dominantly expressed in the stria vascularis, spiral ligament, spiral limbus and organ of Corti. A subsequent study showed that experimental animals injected with c-raf protein developed lymphadenopathy, skin lesions, abnormal gait, splenomegaly and hyperimmunoglobulinemia almost resembling a full blown autoimmune disease like Lupus Erythematosus. This information stirred interest whether the autoantibodies
10
This has been a common practice outside the United States prior to December 2000.
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detected in the study are present in patients with Systemic Lupus Erythematosus. Raf proteins are serine/threonine specific protein kinases which play a critical role in intracellular signaling downstream from many tyrosine kinase and G-protein-linked receptors. c-Raf binds to Ras in a GTP-dependent manner and signal transduction pathway involving this is frequently activated in tumor cells. This information added more interest in pursuing the study with SLE patients and perhaps other patients population. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Human FcgammaRIIB gene polymorphisms for assessing development of systemic lupus erythematosus and compositions for use thereof Inventor(s): Pricop, Luminita; (New York, NY) Correspondence: DARBY & DARBY P.C. 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030162180 Date filed: February 26, 2002 Abstract: The present invention provides methods for predicting the likelihood of development of systemic lupus erythematosus (SLE) in an individual, which comprise determining the sequence at one or more polymorphic positions within the human genes encoding Fc.gamma.RIIB. The invention also provides isolated nucleic acids encoding Fc.gamma.RIIB polymorphisms, nucleic acid probes that hybridize to polymorphic positions and kits for the prediction of SLE status. Excerpt(s): The present invention relates to genetic polymorphisms and polymorphism patterns useful for assessing development of systemic lupus erythematosus in humans. More particularly, the invention relates to identifying and using polymorphism patterns comprising a polymorphism in the human Fc.gamma.IIB receptor to predict a treatment outcome or likelihood of developing systemic lupus erythematosus, and to assist in diagnosis and in prescription of an effective therapeutic regimen. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that can affect various parts of the body including skin, blood, kidney, and joint. SLE may be a mild disease, however, may also be serious and life-threatening. More than 16,000 cases of SLE are reported in the United States each year, with up to 1.5 million cases diagnosed. Although SLE can occur at any age, and in either sex, it has been found to occur 1-15 times more frequently in women. SLE is a prototypic immune complex disease with defects in both the humoral and efferent pathways of the immune response. Autoreactive lymphocytes initiate the process of autoantibody production and ultimately lead to formation of immune complexes. Binding of immune complexes to specific cellular receptors, called Fc receptors, can potentially modify the development or progression of SLE by altering the response of either B cell or mononuclear phagocytes to immune complex-mediated inflammation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Identification of farnesyl-protein transferase as a target for systemic lupus erythematosus therapies Inventor(s): Liu, Kui; (Plano, TX), Wakeland, Ward; (Dallas, TX) Correspondence: FULBRIGHT & JAWORSKI L.L.P. A REGISTERED LIMITED LIABILITY PARTNERSHIP; SUITE 2400; 600 CONGRESS AVENUE; AUSTIN; TX; 78701-3271; US Patent Application Number: 20020177575 Date filed: May 3, 2002 Abstract: The invention relates to the identification of farnesyl-protein transferase (FPT) as a gene that is upregulated in systemic lupus erythematosus (SLE). Given the widespread availability of inhibitors of FPT, the inventors propose to treat the symptoms of SLE using such inhibitors. Excerpt(s): This application claims benefit of priority to U.S. Provisional Serial No. 60/288,868, filed on May 4, 2001, the entire contents of which are incorporated by reference herein. The federal government owns certain rights in this application by virtue of grant support for the National Institutes of Health (NIH A1-39824). The present invention relates generally to the fields of molecular biology and pathology. More particularly, it concerns the identification of genes involved in the breakdown of immune tolerance leading to the development of systemic autoimmunity, particularly systemic lupus erythematosus (SLE), and methods of treating SLE based thereon. Systemic lupus erythematosus (SLE) is mediated by a complex interaction of genetic and environmental elements. Although the crucial role of genetic predisposition in susceptibility to SLE has been known for decades, only minimal progress has been made towards elucidating the specific genes involved in human disease. Recently, several groups have reported linkage analyses that provide estimates of the number and chromosomal locations of at least some of the susceptibility genes for human SLE. These studies have provided interesting insights into the complexity of the genetic interactions involved in SLE but have not resulted in the identification of specific genes or genetic pathways involved in disease pathogenesis. This reflects the difficulties inherent in the analysis of complex genetic diseases, coupled with the absence of sample repositories of sufficient size to allow definitive genetic analysis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Localization of major peptide autoepitopes for nucleosome specific T cells of systemic lupus erythematosus Inventor(s): Datta, Syamal K. (Winnetka, IL), Kaliyaperumal, Arunan; (Skokie, IL) Correspondence: MORGAN, LEWIS & BOCKIUS LLP; 1701 MARKET STREET; PHILADELPHIA; PA; 19103-2921; US Patent Application Number: 20030021797 Date filed: August 2, 2002 Abstract: The present invention includes peptides derived from nucleosomal histone proteins which are useful for delaying the onset and progression of systemic lupus erythematosus (i.e. lupus or SLE). The peptides of the invention span the histone proteins (i.e. H1, H2A, H2B, H3, and H4). The invention additionally encompasses isolated nucleic acids which encode these histone peptides as well as pharmaceutical
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compositions which comprise one or more of a histone peptide. Further, the invention provides kits which comprise one or more histone peptides or isolated nucleic acids encoding histone peptides and an instructional material. The invention also provides methods of using these compositions and analogs of histone peptides to inhibit an immune response and associated inflammation in an animal and to treat disorders in an animal which are related to the production of autoantibodies and complications thereof, such as inflammatory diseases, autoimmune disorders, and nephritis. In addition, the invention includes methods for developing diagnostic and prognostic reagents using the histone peptides and isolated nucleic acids encoding the instone peptides, for the purpose of tracking autoimmune T helper cells and B cells of SLE are also included. Excerpt(s): This application is entitled to priority pursuant to 35 U.S.C.sctn.119(e) to U.S. Provisional Patent Application No. 60/131,448, which was filed on Apr. 28, 1999. Nucleosome-specific T helper cells (Th cells) initiate and sustain the production of pathogenic, anti-nuclear autoantibodies during the onset and progression of systemic lupus erythematosus (SLE) through cognate interaction with autoimmune B cells (Mohan et al., 1993, J. Exp. Med. 177:1367; Desai-Mehta et al., 1995, J. Clin. Invest. 95:53; Kaliyaperumal et al., 1996, J. Exp. Med. 183:2459; Shi et al., 1998, J. Exp. Med. 187:367; Voll et al., 1997, Arthritis Rheum. 40:2162; Kretz-Rommel, et al., 1997, J. Clin. Invest. 99:1888). These SLE-associated Th cells are primarily responsible for driving the pathogenic autoimmune response. Without the help provided by these Th cells, autoimmune B cells are unable to produce the disease-causing (pathogenic) autoantibodies associated with SLE. Some of the critical epitopes (i.e. autoantigenic determinants) to which these Th cells are directed have been localized to the histone proteins of nucleosomes (i.e. DNA-protein complexes in the nuclei of animal cells). For example, in lupus prone mice, SLE-associated autoepitopes have been identified at amino acid positions 10-33 of the H2B histone protein, at amino acid positions 85-102 of the H3 histone protein, and at amino acid positions 16-39 and 71-94 of the H4 histone protein (Kaliyaperumal et al., 1996, J. Exp. Med. 183:2459). Autoimmune T cells of lupusprone mice are spontaneously primed to SLE-associated autoepitopes early in life before overt autoantibody production or any clinical manifestations of the disease are present (Kaliyaperumal et al., 1996, J. Exp. Med. 183:2459). Moreover, immunization of preautoimmune mice with peptides corresponding to SLE-associated nucleosomal autoepitopes precipitates SLE-associated nephritis by triggering autoimmune T helper cells of subtype 1 (i.e. Th 1 cells) which, in turn, initiate anti-nuclear autoantibody production (Kaliyaperumal et al., 1996, J. Exp. Med. 183:2459). The T helper cell subtypes 2 and 0 (i.e., Th2 and Th0 cells, respectively) are also involved in the progression of SLE, as these T helper cell subtypes maintain autoantibody production (Mohan et al., 1993, J. Exp. Med. 177:1367; Nakajima et al., 1997, J. Immunol. 158:1466). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for diagnosing and treating systemic lupus erythematosus disease and compositions thereof Inventor(s): O''Toole, Margot; (Newton, MA), Legault, Holly; (Woburn, MA) Correspondence: MINTZ, LEVIN, COHN, FERRIS; GLOVSKY and POPEO, P.C. One Financial Center; Boston; MA; 02111; US Patent Application Number: 20030148298 Date filed: April 3, 2002
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Abstract: The present invention is directed to novel methods for diagnosis and prognosis of Systemic lupus erythematosus by identifying differentially expressed genes. Moreover, the present invention is also directed to methods that can be used to screen test compounds and therapies for the ability to inhibit systemic lupus erythematosus. Additionally, methods and molecule targets (genes and their products) for therapeutic intervention in systemic lupus erythematosus are described. Excerpt(s): This application claims priority to U.S. Ser. No. 60/281,515, filed Apr. 3, 2001. The contents of this application are incorporated herein by reference in their entirety. The present invention is directed to novel methods for diagnosis and prognosis of Systemic Lupus Erythematosus by identifying differentially expressed genes. The present invention is further directed to methods and molecular targets (genes and their products) for therapeutic intervention in systemic lupus erythematosus. In particular, the present invention is directed to a method of modulating the expression levels of genes associated with systemic lupus erythematosus by administration of rapamycin or antibodies to B7 molecules. Systemic Lupus Erythematosus (SLE) is a chronic automimmmune disorder in which patients suffer a number immunological abnormalities that is not specific to any one organ. SLE is manifested in various forms, including facial lesions, nephritis, endocarditis, hemolytic anemia and leukopenia. Specifically, SLE has been linked to disruption of complex T-cell mediated pathways, thus presenting a challenge to researchers attempting to elucidate the mechanism of the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for treatment of lupus erythematosus Inventor(s): Thompson, W. Joseph; (Doylestown, PA), Whitehead, Clark M. (Warminster, PA), Alila, Hector W. (North Wales, PA), Earle, Keith A. (North Wales, PA) Correspondence: Robert W. Stevenson; Cell Pathways, Inc. 702 Electronic Drive; Horsham; PA; 19044; US Patent Application Number: 20030073740 Date filed: August 23, 2001 Abstract: Substituted condensation products of N-benzyl-3-indenylacetamides with heterocyclic aldehydes and other such inhibitors are useful for the treatment of lupus erythematosus. Excerpt(s): This invention relates to the treatment of lupus erythematosus. There are three types of lupus: drug-induced, discoid, and systemic. Drug-induced lupus occurs after the use of certain prescribed drugs. The symptoms of drug-induced lupus are similar to those of systemic lupus. The drugs most commonly connected with druginduced lupus are hydralazine (used to treat high blood pressure or hypertension) and procainamide (used to treat irregular heart rhythms). Drug-induced lupus is more common in men who are given these drugs more often. However, not everyone who takes these drugs will develop drug-induced lupus. Only about 4 percent of the people who take these drugs will develop the antibodies suggestive of lupus. Of those 4 percent, only an extremely small number will develop overt drug-induced lupus. The symptoms usually fade when the medications are discontinued. Discoid (cutaneous) lupus is limited to the skin. It is identified by a rash that may appear on the face, neck, and scalp. Discoid lupus is diagnosed by examining a biopsy of the rash. In discoid
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lupus the biopsy will show abnormalities that are not found in normal skin. Discoid lupus does not generally involve the body's internal organs, so it is a generally manageable disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of treating systemic lupus erythematosus in individuals having significantly impaired renal function Inventor(s): Linnik, Matthew D. (Solana Beach, CA), Hepburn, Bonnie; (Escondido, CA) Correspondence: Catherine M. Polizzi; Morrison & Foerster LLP; 755 Page Mill Road; Palo Alto; CA; 94304-1018; US Patent Application Number: 20030114405 Date filed: August 13, 2002 Abstract: The invention provides methods treating lupus nephritis based in individuals with significantly impaired renal function, and methods of selecting individuals for treatment based on significantly impaired renal function. The treatment entails administration of a conjugate comprising a non-immunogenic valency platform molecule and at least two double stranded DNA epitopes, such as DNA molecules, which bind to anti-DNA antibodies from the patient. The invention also provides methods of identifying individuals suitable for treatment for lupus, based on assessing renal function to identify those individuals with significant impairment of renal function. Excerpt(s): This application claims priority under 35 U.S.C.sctn.119(e) to U.S. Provisional Patent Application Serial No. 60/311,858, filed Aug. 13, 2001, and to U.S. Provisional Patent Application Serial No. 60/314,281, filed Aug. 22, 2001, each of which is hereby incorporated by reference in its entirety. This invention relates to the field of antibodymediated pathologies such as lupus. More particularly, the invention relates to methods of treating individuals with systemic lupus erythematosis having significantly impaired renal function. Systemic lupus erythematosis (SLE) is an autoimmune disease characterized by the production of antibodies to a number of nuclear antigens, including double-stranded DNA (dsDNA). Autoantibodies that react with DNA are believed to play a role in the pathology of SLE and are closely associated with lupus nephritis. See, for example, Morimoto et al. (1982) J. Immunol. 139:1960-1965; Foster et al. (1993) Lab. Invest. 69:494-507; ter Borg et al. (1990) Arthritis Rheum. 33:634-643; Bootsma et al. (1995) Lancet 345:1595-1599. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Preventive and/or therapeutic agent for systemic lupus erythematosus comprising anti-IL-6 receptor antibody as an active ingredient Inventor(s): Mihara, Masahiko; (Gotenba-shi, JP), Ohsugi, Yoshiyuki; (Niihari-gun, JP) Correspondence: FOLEY AND LARDNER; SUITE 500; 3000 K STREET NW; WASHINGTON; DC; 20007; US Patent Application Number: 20020187150 Date filed: May 10, 2002
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Abstract: A preventive and/or therapeutic agent for systemic lupus erythematosus comprising an anti-interleukin-6 (IL-6) receptor antibody as an active ingredient. Excerpt(s): The present invention relates to a preventive and/or therapeutic agent for systemic lupus erythematosus comprising an anti-interleukin-6 receptor antibody as an active ingredient. Interleukin-6 (IL-6) is a cytokeine which is also called B cell stimulating factor 2 (BSF2) or interferon.beta.2 (IFN-.beta.2). IL-6 was discovered as a differentiation factor involved in the activation of B lymphocytes (Hirano, T. et al., Nature (1986) 324, 73-76). Thereafter, it was found to be a multifunctional cytokeine that influences various functions of the cells (Akira, S. et al., Adv. in Immunology (1993) 54, 1-78). IL-6 transmits its biological activity through two types of proteins on the cell. One is IL-6 receptor, a ligand-biding protein to which IL-6 binds. IL-6 receptor occurs not only as a membrane-bound IL-6 receptor, molecular weight of about 80 kD, that penetrates through and is expressed on the cell membrane but also as a soluble IL-6 receptor, molecular weight of about 40 to 50 kD, essentially consisting of the extracellular region. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of anti-gp-39 antibodies for treatment and/or reversal of lupus and lupus associated kidney disease Inventor(s): Burns, Christopher M. (Lyme, NH), Noelle, Randolph J. (Cornish, NH) Correspondence: Pillsbury Winthrop LLP; Intellectual Property Group; East Tower, Ninth Floor; 1100 New York Avenue, N.W. Washington; DC; 20005-3918; US Patent Application Number: 20020058037 Date filed: May 16, 2001 Abstract: A method of treating lupus using anti-gp39 antibodies or fragments is provided. Such treatment has been shown to reverse disease, and in particular lupusassociated kidney disease, the major killer of lupus subjects. Excerpt(s): This application is a continuation of U.S. Ser. No. 09/054,488, filed Apr. 3, 1998, which is a continuation-in-part of U.S. Ser. No. 08/742,480, filed Nov. 1, 1996, which, in turn, is a continuation of Ser. No. 08/338,975, filed Nov. 14, 1994, abandoned, in turn, a continuation of Ser. No. 07/835,799, filed Feb. 14, 1992, now abandoned. The present invention relates to a counter-receptor, referred to alternatively in the literature as CD40CR, gp39, or most recently CD154 for the CD40 B-cell antigen, and to soluble ligands for this receptor, including fusion molecules comprising at least a portion of CD40 protein. It is based, at least in part, on the discovery that a soluble CD40/immunoglobulin fusion protein was able to inhibit helper T-cell mediated B-cell activation by binding to a novel 39 kD protein receptor on helper T-cell membranes. The present invention provides for a substantially purified CD40CR receptor; for soluble ligands of CD40CR, including anti-gp39 antibodies and fragments thereof, as well as fusion molecules comprising at least a portion of CD40 protein; and for methods of controlling B-cell activation which may be especially useful in the treatment of allergy or autoimmune disease. More specifically, the present invention relates to the use of antigp39 antibodies for treating systemic lupus erythematosus (SLE) or drug induced lupus. Studies by Mitchison, Benacerraf and Raff first suggested that physical interactions between T.sub.h and B-cells were essential in the development of humoral immune responses. Later studies documented that T.sub.h formed physical conjugates with class II major histocompatibility complex (MHC) compatible, antigen-presenting B-cells
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(Vitetta et al., Immunol. Rev., 99:193-239 (1987)) and that it was the B-cells within these conjugates that responded to T.sub.h (Barrett et al., J. Immunol., 143:1745-1754 (1989)). With the discovery that T.sub.h-derived lymphokines exerted potent growth and differentiative effects on B-cells, it was proposed that soluble factor(s) released in proximity by activated T.sub.h mediated the activation of the interacting B-cell. However, none of the molecularly cloned lymphokines, alone or in combination, manifested the ability to induce B-cell cycle entry. Unlike soluble factors, plasma membrane fractions from activated T.sub.h induced B-cell cycle entry (Hodgkin et al., J Immunol., 145:2025-2034 (1990); Noelle et al., J. Immunol., 146:1118-1124 (1991)). Studies using purified plasma membrane fractions from activated Th suggested that a protein expressed on the membrane of activated Th was responsible for initiating humoral immunity (Noelle et al., J. Immunol., 146:1118-1124 (1991); Bartlett et al., J. Immunol., 145:3956-3962 (1990)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of growth hormone secretagogues to treat systemic lupus erythematosus and inflammatory bowel disease Inventor(s): Pan, Lydia C. (Mystic, CT), Lefker, Bruce A. (Gales Ferry, CT), Busch, Frank Robert; (Gales Ferry, CT) Correspondence: Gregg C. Benson; Pfizer Inc. Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20020013320 Date filed: June 14, 2001 Abstract: This invention is directed to methods for treating systemic lupus erythematosus and/or inflammatory bowel disease such as Crohn's disease or ulcerative colitis in a patient which comprise administering a growth hormone secretagogue (GHS), prodrug thereof or a pharmaceutically acceptable salt of said GHS or said prodrug. More particularly, the present invention provides such methods wherein the GHS is a compound of Formula I: 1or a prodrug thereof or a pharmaceutically acceptable salt of said GHS or said prodrug. This invention is also directed to combinations of a GHS and a second therapeutic agent, where said second therapeutic agent is known to be beneficial in the treatment of systemic lupus erythematosus and/or inflammatory bowel disease such as Crohn's disease or ulcerative colitis, to kits and pharmaceutical compositions comprising such a combination and to methods of treating systemic lupus erythematosus and/or inflammatory bowel disease such as Crohn's disease or ulcerative colitis using such combinations, pharmaceutical compositions and kits. Excerpt(s): This application claims priority from the provisional application U.S. Ser. No. 60/212,521, filed on Jun. 19, 2000, the benefit of which is hereby claimed under 37 C.F.R.sctn.1.78(a)(3). The present invention provides methods of using growth hormone secretagogues, prodrugs thereof and pharmaceutically acceptable salts of said secretagogues and said prodrugs to treat systemic lupus erythematosus, Crohn's disease, inflammatory bowel disease (IBD) and ulcerative colitis. More specifically, the present invention provides such methods wherein the growth hormone secretagogues are certain compounds of Formula I below. This invention also provides combinations comprising a growth hormone secretagogue and a second therapeutic agent selected from methotrexate, dapsone, a glucocorticoid or an antimalarial. The invention also provides pharmaceutical compositions and kits comprising such combinations and
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methods of using such combinations, pharmaceutical compositions and kits in the treatment of systemic lupus erythematosus, Crohn's disease, IBD and ulcerative colitis. The origin of autoantibody production in SLE is unclear but a role has been suggested for an antigen driven process, spontaneous B-cell hyper-responsiveness, or impaired immune regulation. Regardless of the etiology of autoantibody production, SLE is associated with the impaired clearance of circulating immune complexes secondary to decreased CR1 expression, defective Fc receptor function, or deficiencies of early complement components such as C4A. (Belmont, ibid.) It has been suggested that the apoptosis process is atypical in the lupus patient leading to the increased production of autoantibodies including antiphospholipid antibodies. (L. Casciola-Rosen et al., Proc. Natl. Acad. Sci. USA, 93, 1996, 1624-1629. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with lupus, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “lupus” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on lupus. You can also use this procedure to view pending patent applications concerning lupus. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON LUPUS Overview This chapter provides bibliographic book references relating to lupus. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on lupus include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “lupus” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on lupus: •
Lupus: Everything You Need to Know Source: Garden City Park, NY: Avery Publishing Group. 1998. 238 p. Contact: Available from Avery Publishing Group. 120 Old Broadway, Garden City Park, NY 11040. (800) 548-5757. PRICE: $12.95 plus shipping and handling. ISBN 0895298333. Summary: This book for people with lupus and their families uses a question and answer format to provide clear and concise information about this autoimmune disease. Chapter 1 presents an overview of lupus, focusing on the nature of lupus; the features of the three kinds of lupus; the causal factors involved; the progression of the disease; and its triggers. The next chapter answers questions about the diagnosis of lupus, focusing on common tests such as the antinuclear antibody test, the anti-deoxyribonucleic acid test, the anticardiolipin antibody test, and the anti-Smith test. It also identifies important factors in diagnosing lupus, visualization, and other procedures that are helpful in the diagnosis of lupus. The third chapter focuses on the symptoms of lupus, including
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common symptoms; complications of the joints and muscles, skin, kidneys, nervous system, blood, cardiovascular system, lungs, gastrointestinal system, reproductive system, mouth, and eyes; aches and pains; sun sensitivity; infections; and fatigue. Chapter 4 provides answers to questions about the methods of treating lupus, other than medication, focusing on physical therapy, plasmapheresis, alternative medicine, diet, and rest and exercise. The focus of the next chapter is on medications used to treat lupus, including aspirin, nonsteroidal anti-inflammatory drugs, antimalarials, corticosteroids, immunosuppressants, and dehydroepiandrosterone. The final chapter answers questions about the impact of lupus on sexual activity, pregnancy, family life, and work. An appendix lists sources of additional information. •
Coping with Lupus Source: Garden City Park, NY: Avery Publishing Group. 1991. 276 p. Contact: Available from Avery Publishing Group. 120 Old Broadway, Garden City Park, NY 11040. (800) 548-5757 or (516) 741-2155. Fax (516) 742-1892. E-mail:
[email protected]. Website: www.averypublishing.com. PRICE: $12.95 plus shipping and handling. ISBN: 0895294753. Summary: This book offers lupus patients a guide to adapting to life with systemic lupus erythematosus (SLE). The first part of the book presents background information on lupus: what it is, how it is diagnosed, and treatment options. The other main parts deal with different aspects of living with lupus, including coping with emotions, changes in lifestyle, and living with others. Specific chapters are offered on the child and adolescent with lupus. The author stresses that, just as the symptoms of lupus are different in each person, the psychological effects of having lupus also vary with each person who is diagnosed with the illness. Suggestions for strategies and techniques to try are offered in the areas of physical changes, rest and exercise, weight changes and diet, activities, pain, financial problems, traveling, quackery, sexuality, dealing with family members, pregnancy, emotions, dealing with friends and colleagues, and stress management. Throughout the book, the author offers vignettes of lupus patients who have struggled with different issues and explains how they coped with their own situations. The book concludes with an appendix listing a few resources and a subject index.
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Challenges of Lupus: Insights and Hope Source: Garden City Park, NY: Avery Publishing Group. 1999. 255 p. Contact: Available from Penguin-Putnam, Inc. Consumer Sales, 405 Murray Hill Parkway, East Rutherford, NJ 07073. (800) 788-6262. PRICE: $14.95 plus shipping and handling. ISBN 0895298813. Summary: This book provides people who have lupus with information that will help them take better care of themselves by better understanding their disease. The book is a compilation of 40 articles written by experts on the subject of lupus. The book is organized into six parts. Part 1, which serves as an introduction to lupus, provides readers with an overview. Topics include the epidemiology, manifestations, diagnosis, etiology, and management of lupus. Part 2 recounts the author's personal experiences and the experiences of others with lupus. Part 3 discusses the way lupus affects different groups of people at different stages of life, including newborns, children, women, men, the elderly, and pregnant women. Part 4 explains the different manifestations of lupus, such its effects on the lungs, the skeletal system, the central nervous system, the heart and blood vessels, the blood, and the skin. Part 5 details the medications that are used in
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the treatment of lupus, including corticosteroids, nonsteroidal antiinflammatory drugs, antimalarial drugs, and cytotoxic drugs. Other topics include the development of drug induced lupus; the treatment of blood disorders, pain, and psychiatric, neurologic, cardiovascular, renal, cutaneous, and gastrointestinal manifestations; the psychiatric side effects of lupus medications; the use of placebos; and the role of a kidney biopsy. Part 6 examines the importance of the physician patient relationship. The book includes a glossary and a list of local chapters of the Lupus Foundation of America. 41 references. •
Living Well: Despite Lupus! Source: Hicksville, NY: Balance Enterprises, Inc. 1996. 58 p. Contact: Lupus Foundation of America, Inc., Western Pennsylvania Chapter, 1323 Forbes Avenue, Suite 200, Pittsburgh, PA 15219. (412) 261-5886. (800) 800-5776. (412) 472-2722 (fax). Summary: This book teaches individuals with lupus 204 effective techniques for helping themselves to feel better. An introductory section provides an overview of lupus. Subsequent sections offer strategies for preparing for one's lupus self-improvement program; working on the way lupus affects one's physical symptoms; understanding the role and benefit of medication; taking care of one's body by eating a healthy, nutritious diet, getting enough exercise, avoiding inappropriate, addictive-type behaviors, and getting enough sleep; using relaxation and imagery techniques; working on the way lupus affects one's day-to-day living, activities, emotions, self-esteem, and relationships; and taking advantage of resources to live well despite lupus.
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Lupus: A Patient Care Guide for Nurses and Other Health Professionals Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1998. 146 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail:
[email protected]. Website: www.niams.nih.gov. PRICE: 1 to 25 copies free. Order Number: AR-204. Summary: This guide provides health professionals with an overview of lupus and what is involved in caring for patients who have it. Chapter one focuses on the features of discoid lupus erythematosus, systemic lupus erythematosus (SLE), and drug-induced SLE; the symptoms, diagnosis, and treatment of SLE; medications; and psychosocial aspects. The implications of these aspects for the way nurses or other health professionals work with a patient who has lupus are discussed as well. Chapter two highlights some recent research advances in terms of the role of immune system dysfunction, genetics, environmental influences, and hormones in the etiology of Systemic Lupus Erythematosus. It also reviews ongoing research in treatment and health maintenance and discusses the role of the National Institute of Arthritis and Musculoskeletal and Skin Diseases in lupus research. Chapter three describes the major tests used to diagnose and evaluate SLE, including blood tests, autoimmunity measurements, and tests for kidney disease. It also provides information on the rationale for using these tests and their clinical usefulness. Chapter four provides an overview of general and system specific lupus manifestations, as well as potential problems and nursing interventions for each. Among the general manifestations are fatigue, fever, and psychological and emotional effects. Specific manifestations include dermatologic, musculoskeletal, hematologic, cardiopulmonary, renal, central nervous
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system, gastrointestinal, and ophthalmologic abnormalities. Several key issues, including pregnancy, infection, and nutrition, are also discussed. Chapter five reviews the major categories of medications used to treat lupus, including nonsteroidal antiinflammatory drugs, antimalarials, corticosteroids, and immunosuppressives. Chapter six examines the psychosocial aspects of lupus, including helping a patient cope with the emotional needs associated with seeking a diagnosis; handling the reactions of family members and oneself; and gaining control over feelings, emotions, and new physical limitations. Chapter seven presents 16 short fact sheets covering a broad range of issues related to living with lupus and using medications to manage it. The final chapter identifies organizations and written materials that may be useful as sources of further information about lupus and patient care. The guidebook concludes with an index. 54 references. •
Lupus Handbook for Women: Up-to-date Information on understanding and Managing the Disease which Affects 1 in 500 Women Source: New York, NY: Fireside. 1994. 176 p. Contact: Available from Fireside, Rockefeller Center, 1230 Avenue of the Americas, New York, NY 10020. PRICE: $10.00 in the U.S., $13.00 in Canada. Summary: This handbook for women with lupus helps educate them about their illness. Chapters discuss the causes and symptoms of lupus, describe the 11 criteria for diagnosing systemic lupus erythematosus (SLE), examine the role of the physical examination and laboratory tests in the diagnosis of SLE, identify common complications of SLE and discuss their diagnosis and treatment, describe drug and experimental therapies for treating SLE, and offer guidelines for managing and preserving one's health. Chapters also provide suggestions for maintaining a healthy lifestyle, examine the impact of lupus on intimate relationships, identify the factors that women with lupus should consider before becoming pregnant and address issues that they should consider during pregnancy, and offer advice for coping with lupus. A list of resources is also provided. 16 references.
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Lupus Eritematoso: Manual para medicos, pacientes y familiares, 2a. Edicion Source: Washington, DC: La Fundacion Americana para el Lupus. 1998. 66 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 toll-free or (301) 670-9292. Website: www.lupus.org/lupus. PRICE: $3.00 plus shipping and handling. Summary: This illustrated handbook, written in Spanish, provides health professionals and patients who have lupus and their families with information on this chronic immune system disease. The handbook begins by describing the types of lupus, including discoid lupus and systemic lupus erythematosus. This is followed by information on incidence and prevalence and some common symptoms. Other topics include the cause of lupus, diagnosis based on clinical evidence, the role of heredity, pregnancy and lupus, exacerbation and remission, treatment options, and prognosis. In addition, the handbook discusses the importance of a balanced diet, treatments under investigation, and the activities of the American Foundation for Lupus and the National Institutes of Health. The handbook concludes with a list of recommended readings.
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Lupus Book: A Guide for Patients and Their Families, Revised and Expanded Edition Source: New York, NY: Oxford University Press. 2000. 283 p.
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Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 toll-free or (301) 670-9292. Website: www.lupus.org/lupus. PRICE: $21.95 plus shipping and handling; bulk discount available. Summary: This revised and expanded version of a book first published in 1995 provides patients with lupus and their families with reliable, up to date information that will help them manage the disease and live a better life. Part 1 explains how lupus is defined and classified, explores the historical context of the disease, and provides an overview of its epidemiology. Part 2 focuses on how lupus damages body tissue and why it occurs. Topics include the components of the normal inflammatory and immune system and the features unique to lupus and other autoimmune processes that alter this system to cause tissue injury. Part 3 focuses on etiology. Topics include the genetic aspects of lupus; environmental factors that act as inciting agents, such as chemical agents, foods, ultraviolet radiation, and infectious agents; drugs that exacerbate lupus such as antibiotics, nonsteroidal antiinflammatory drugs, and hormones; and drugs that cause drug induced lupus. Part 4 takes the reader through the diagnosis, using an approach that considers symptoms, signs, and conditions affecting the blood, the skin, the musculoskeletal system, the lung, the heart, the nervous system, the head and neck, the gastrointestinal tract, the kidneys, the urinary tract, and the lymphatic system. The differential diagnosis of lupus is also considered. Part 5 focuses on the management of lupus. Topics include the effect of sunlight, diet, exercise, heat, rest, and climatic conditions; the principal psychosocial problems that patients with lupus encounter and ways to deal with them; the use of nonsteroidal antiinflammatory drugs and disease modifying antirheumatic drugs; and the use of other drugs for short periods. Other topics include the management of infections, allergies, and osteoporosis; the impact of lupus on a pregnancy; the prognosis for people who have lupus; and future medical advances. The book includes a glossary and a list of resource materials. •
Successful Living With Lupus: An Action Workbook Source: Hicksville, NY: Balance Enterprises, Inc. 2000. 78 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 toll-free or (301) 670-9292. Website: www.lupus.org/lupus. PRICE: $10.00 plus shipping and handling; bulk discount available. Summary: This workbook provides people who have lupus with worksheets that help them take a positive, empowering approach to improving their emotional and social well being. A general strategies section focuses on learning about lupus, pinpointing areas to improve, setting goals for self improvement, and using relaxation techniques. A section on the body deals with performing a body inventory, determining strengths, improving nutritional status and sleeping habits, and exercising for improved health. A symptoms section offers worksheets on keeping a symptom or discomfort log, handling medical problems more effectively, monitoring pain numerically, minimizing flares, creating mental images to control pain, dealing with secondary gains, understanding treatment recommendations, learning about medications, handling medication problems or side effects, and preparing for hospitalization. Sections on the psychological aspects of lupus focus on using cognitive restructuring, disrupting irrational thoughts, dealing with negative thoughts, using positive affirmations, using comparisons effectively, joining a support group, keeping a feelings journal, sharing feelings, monitoring stress numerically, identifying depression triggers, using positive self directed statements, changing pessimism into optimism, watching mental movies, using
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various techniques to control anger and guilt, and identifying anxiety triggers. Another section on psychological management deals with self esteem. Worksheets focus on analyzing self esteem, identifying good qualities, and complimenting oneself. A section on relationships includes worksheets on establishing a support network, reducing stressful family interactions, improving family communication, benefiting from gripe time, setting ground rules, modifying one's expectations, scripting what one wants to say, trying to understand the other person's point of view, expressing oneself in a letter, handling people who give advice, controlling sabotage, keeping track of questions for professionals, improving the patient physician partnership, and selecting a health professional. A final section provides worksheets on identifying life changes since the lupus diagnosis, conserving energy, selecting high energy or low energy activities, analyzing the impact of difficult situations, and improving illness related experiences.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “lupus” at online booksellers’ Web sites, you may discover nonmedical books that use the generic term “lupus” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “lupus” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
A Decade of Lupus: Selections from Lupus News by Henrietta Aladjem (Contributor), Malcolm P. Rogers (Introduction); ISBN: 0960866094; http://www.amazon.com/exec/obidos/ASIN/0960866094/icongroupinterna
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A Dictionary for Lupus Patients by Linda K. Rohner (Editor); ISBN: 0963824503; http://www.amazon.com/exec/obidos/ASIN/0963824503/icongroupinterna
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ABC of Asthma, Allergies and Lupus: Eradicate Asthma - Now! by F. Batmanghelidj (2000); ISBN: 096299426X; http://www.amazon.com/exec/obidos/ASIN/096299426X/icongroupinterna
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Advances in Systemic Lupus Erthematosus by John P. Hayslett; ISBN: 0808915606; http://www.amazon.com/exec/obidos/ASIN/0808915606/icongroupinterna
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Australian National Meeting on Lupus Anticoagulant (Hematology Reviews and Communications Series) by S. Roath, M. Corn (Editor); ISBN: 3718649357; http://www.amazon.com/exec/obidos/ASIN/3718649357/icongroupinterna
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Bailliere's Clinical Rheumatology: Systemic Lupus Erythematosus (Bailliere's Internationl Practice and Research) by D. Gladman (Editor), M. Hochberg (Editor); ISBN: 0702024074; http://www.amazon.com/exec/obidos/ASIN/0702024074/icongroupinterna
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Bangun dong, Lupus! by Hilman; ISBN: 9794034029; http://www.amazon.com/exec/obidos/ASIN/9794034029/icongroupinterna
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Collagen-vascular diseases; systemic lupus erythematosus, acute dermatomyositispolymyositis, progressive systemic sclerosis, polyarteritis nodosa by John Harold Talbott; ISBN: 0808908480; http://www.amazon.com/exec/obidos/ASIN/0808908480/icongroupinterna
Books 355
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Connective Tissue Diseases: Lupus, Scleroderma and Rheumatoid Arthritis by Susan Brown (Editor), Robert P. Sundel (Editor) (1994); ISBN: 187977206X; http://www.amazon.com/exec/obidos/ASIN/187977206X/icongroupinterna
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Coping With Lupus by Robert H. Phillips; ISBN: 0895292521; http://www.amazon.com/exec/obidos/ASIN/0895292521/icongroupinterna
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Coping With Lupus: A Guide to Living With Lupus for You and Your Family by Robert H. Phillips (1991); ISBN: 0895294753; http://www.amazon.com/exec/obidos/ASIN/0895294753/icongroupinterna
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Coping With Lupus: A Practical Guide to Alleviating the Challenges of Systemic Lupus Erythematosus by Robert H., Ph.D. Phillips, et al (2001); ISBN: 158333095X; http://www.amazon.com/exec/obidos/ASIN/158333095X/icongroupinterna
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Der Wolf : Canis lupus by D. I. Bibikov; ISBN: 3740301554; http://www.amazon.com/exec/obidos/ASIN/3740301554/icongroupinterna
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Double Lupus by Edik Shenderovich; ISBN: 0970735804; http://www.amazon.com/exec/obidos/ASIN/0970735804/icongroupinterna
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Dubois' Lupus Erythematosus by Daniel J. Wallace (Editor), et al; ISBN: 0683086650; http://www.amazon.com/exec/obidos/ASIN/0683086650/icongroupinterna
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Embracing the Wolf: A Lupus Victim and Her Family Learn to Live With Chronic Disease by Robert H. Gifford (Designer), et al (1994); ISBN: 0877971668; http://www.amazon.com/exec/obidos/ASIN/0877971668/icongroupinterna
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Everything You Need to Know About Lupus (Need to Know Library) by Andre Maraux; ISBN: 0823932885; http://www.amazon.com/exec/obidos/ASIN/0823932885/icongroupinterna
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Expolitation: Homo Homini Lupus by Edmund A. Kurth; ISBN: 0840330243; http://www.amazon.com/exec/obidos/ASIN/0840330243/icongroupinterna
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First Cancer Then Lupus: The Courageous Story of One Woman's Journey Through Illness, Chemotherapy, Steroids & Pain Control by Anne O'Connell; ISBN: 0962727423; http://www.amazon.com/exec/obidos/ASIN/0962727423/icongroupinterna
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God's Plan Included Lupus by Doug Rodgers (Preface), O. D. Rodgers; ISBN: 1561674435; http://www.amazon.com/exec/obidos/ASIN/1561674435/icongroupinterna
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Health Journeys for People With Abridged Rheumatoid Arthritis or Lupus by Belleruth Naparstek (Author); ISBN: 1570420114; http://www.amazon.com/exec/obidos/ASIN/1570420114/icongroupinterna
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Health Journeys: A Guided Meditation To Help You With Rheumatoid Arthritis Or Lupus by Belleruth Naparstek, Steven M. Kohn; ISBN: 1881405257; http://www.amazon.com/exec/obidos/ASIN/1881405257/icongroupinterna
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Heartsearch: Toward Healing Lupus by Donna Hamil Talman, William A. Briggs (Photographer) (1991); ISBN: 1556430728; http://www.amazon.com/exec/obidos/ASIN/1556430728/icongroupinterna
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Homo homini lupus : Markus Lüpertz--Krieg by Markus Lüpertz; ISBN: 398035296X; http://www.amazon.com/exec/obidos/ASIN/398035296X/icongroupinterna
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Immune System Disorders Sourcebook: Basic Information About Lupus, Multiple Sclerosis, Guillain-Barre Syndrome, Chronic Granulomatous Disease, and More, Along Statistical and demographic (Health Reference Series, Vol 18) by Allan R. Cook
356 Lupus
(Editor) (1997); ISBN: 0780802098; http://www.amazon.com/exec/obidos/ASIN/0780802098/icongroupinterna •
Immunosuppression Systematic Lupus Erythematosus by J. Rotstein (Editor), Th Bitter (1974); ISBN: 3805515405; http://www.amazon.com/exec/obidos/ASIN/3805515405/icongroupinterna
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In Search of the Sun: A Woman's Courageous Victory over Lupus by Henrietta Aladjem, Peter H. Schur (Contributor); ISBN: 0684187590; http://www.amazon.com/exec/obidos/ASIN/0684187590/icongroupinterna
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Julius Lupus and the Raiders: Join Julius Lupus the Legionary at Hadrian's Wall (Living in the Past) by Margaret Woodhouse (Illustrator); ISBN: 0707801524; http://www.amazon.com/exec/obidos/ASIN/0707801524/icongroupinterna
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Learning About Lupus: A User Friendly Guide by Mary E. Moore (Editor), et al (1997); ISBN: 0965953009; http://www.amazon.com/exec/obidos/ASIN/0965953009/icongroupinterna
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Living With Lupus: A Comprehensive Guide to Understanding and Controlling Lupus While Getting on With Your Life by Mary Horowitz, et al (1994); ISBN: 0452270561; http://www.amazon.com/exec/obidos/ASIN/0452270561/icongroupinterna
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Living With Lupus: All the Knowledge You Need to Help Yourself by Sheldon Paul Blau, Dodi Schultz (Contributor) (1993); ISBN: 020160809X; http://www.amazon.com/exec/obidos/ASIN/020160809X/icongroupinterna
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Lupus; ISBN: 038504562X; http://www.amazon.com/exec/obidos/ASIN/038504562X/icongroupinterna
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Lupus and You by Eric S. Schned MD; ISBN: 1884153143; http://www.amazon.com/exec/obidos/ASIN/1884153143/icongroupinterna
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LUPUS CAPITAL PLC: International Competitive Benchmarks and Financial Gap Analysis (Financial Performance Series) by Ltd. Icon Group; ISBN: 059708307X; http://www.amazon.com/exec/obidos/ASIN/059708307X/icongroupinterna
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LUPUS CAPITAL PLC: Labor Productivity Benchmarks and International Gap Analysis (Labor Productivity Series) by Ltd. Icon Group; ISBN: 0597259607; http://www.amazon.com/exec/obidos/ASIN/0597259607/icongroupinterna
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Lupus Erythematoles by Schneider; ISBN: 3540009620; http://www.amazon.com/exec/obidos/ASIN/3540009620/icongroupinterna
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Lupus Erythematoles: Information Fur Patienten, Angehorige Und Betreuende by M. Schneider (1993); ISBN: 379850962X; http://www.amazon.com/exec/obidos/ASIN/379850962X/icongroupinterna
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Lupus Erythematosus: A Review of the Current Status of Discoidy Systemic Lupus Erythematosus and Their Varants; ISBN: 0884740005; http://www.amazon.com/exec/obidos/ASIN/0884740005/icongroupinterna
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Lupus Erythematosus: Handbook for Physicians, Patients and Their Families by Ronald I. Carr; ISBN: 0960866027; http://www.amazon.com/exec/obidos/ASIN/0960866027/icongroupinterna
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Lupus Nephritis (Oxford Clinical Nephrology Series) by Edmund J. Lewis (Editor), et al; ISBN: 0192627554; http://www.amazon.com/exec/obidos/ASIN/0192627554/icongroupinterna
Books 357
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Lupus Novice: Toward Self-Healing by Laura Chester, Jesse Stoff; ISBN: 1581770200; http://www.amazon.com/exec/obidos/ASIN/1581770200/icongroupinterna
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Lupus What's It All About? by Claudia Pagano, et al; ISBN: 0966103637; http://www.amazon.com/exec/obidos/ASIN/0966103637/icongroupinterna
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Lupus, a Wolf in Sheep's Clothing by Keren Hardy; ISBN: 0859243699; http://www.amazon.com/exec/obidos/ASIN/0859243699/icongroupinterna
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Lupus: A Patient Care Guide for Nurses and Other Health Professionals by Terri Nass, et al (2000); ISBN: 0756700620; http://www.amazon.com/exec/obidos/ASIN/0756700620/icongroupinterna
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Lupus: Alternative Therapies That Work by Sharon Moore (2000); ISBN: 0892818891; http://www.amazon.com/exec/obidos/ASIN/0892818891/icongroupinterna
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Lupus: Everything You Need to Know by Robert G. Lahita, Robert H. Phillips (1998); ISBN: 0895298333; http://www.amazon.com/exec/obidos/ASIN/0895298333/icongroupinterna
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Lupus: Living With It by Suzy Living With It Szasz (1995); ISBN: 1573920231; http://www.amazon.com/exec/obidos/ASIN/1573920231/icongroupinterna
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Lupus: Molecular and Cellular Pathogenesis by Gary M. Kammer (Editor), George C. Tsokos (Editor); ISBN: 0896035565; http://www.amazon.com/exec/obidos/ASIN/0896035565/icongroupinterna
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Lupus: My Search for a Diagnosis by Eileen Radziunas, Jackie Melvin (Editor) (1990); ISBN: 0897930657; http://www.amazon.com/exec/obidos/ASIN/0897930657/icongroupinterna
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Lupus: The Body Against Itself by Sheldon P., Md. Blau, Dodi Schultz; ISBN: 0385188005; http://www.amazon.com/exec/obidos/ASIN/0385188005/icongroupinterna
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Lupus: the Facts by Graham R. V. Hughes; ISBN: 0192631454; http://www.amazon.com/exec/obidos/ASIN/0192631454/icongroupinterna
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Ms. Lupus and Me: And That's Not All by Bess Kossoudji Harvey (1992); ISBN: 0964063506; http://www.amazon.com/exec/obidos/ASIN/0964063506/icongroupinterna
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My Adventure With Lupus: Living With a Chronic Illness by Robert L. Yocum (1995); ISBN: 1882180453; http://www.amazon.com/exec/obidos/ASIN/1882180453/icongroupinterna
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Neuropsychiatric Manifestations of Systemic Lupus Erythematosus (Annals of the Ny Academy of Sciences) by Patricia M. Moore (Editor), Robert G. Lahita (Editor) (1999); ISBN: 0801862167; http://www.amazon.com/exec/obidos/ASIN/0801862167/icongroupinterna
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New Hope for People with Lupus: Your Friendly, Authoritive Guide to the Latest in Traditional and Complementary Solutions by Theresa Foy Digeronimo, et al (2002); ISBN: 076152097X; http://www.amazon.com/exec/obidos/ASIN/076152097X/icongroupinterna
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Nicki the Lupus in Me by Lois'E Hall (2002); ISBN: 140332929X; http://www.amazon.com/exec/obidos/ASIN/140332929X/icongroupinterna
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Pathology of Systemic Lupus by Tatiana T. Antonovych (1995); ISBN: 1881041239; http://www.amazon.com/exec/obidos/ASIN/1881041239/icongroupinterna
358 Lupus
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Patient Education Booklets: What You Should Know About Arthritic Disorders: Osteoarthritis/rheumatoid Arthritus/systemic Lupus Erythematosis (Patient Education Booklets) by Brian Kotzin MD, Herbert Kaplan MD; ISBN: 1563751097; http://www.amazon.com/exec/obidos/ASIN/1563751097/icongroupinterna
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Progress in Allergy: Immunology of Anergy Systemic Lupus Erythematosus by R. Schwartz (Editor) (1985); ISBN: 3805538243; http://www.amazon.com/exec/obidos/ASIN/3805538243/icongroupinterna
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Pumpkin: A Young Woman's Struggle With Lupus by Patricia M. Fagan, Adolfo Caso (Editor) (1994); ISBN: 0828319618; http://www.amazon.com/exec/obidos/ASIN/0828319618/icongroupinterna
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Recent Advances in Systemic Lupus Erythematosus by L. Perrin (Editor), et al (1997); ISBN: 0124346200; http://www.amazon.com/exec/obidos/ASIN/0124346200/icongroupinterna
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Red Butterfly: Lupus Patients Can Survive by Linda R. Bell; ISBN: 0828319405; http://www.amazon.com/exec/obidos/ASIN/0828319405/icongroupinterna
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Status and Conservation Needs of the Wolf (Canis Lupus) in the Council of Europe Member States (Nature and Environment Series) by Miguel Delibes; ISBN: 9287118639; http://www.amazon.com/exec/obidos/ASIN/9287118639/icongroupinterna
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Successful Living with Lupus by Robert H. Phillips; ISBN: 1888614080; http://www.amazon.com/exec/obidos/ASIN/1888614080/icongroupinterna
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Systematic Lupus Erythematosus: Clinical and Theoretical Aspects by J.L. Verbov, et al (1973); ISBN: 084227104X; http://www.amazon.com/exec/obidos/ASIN/084227104X/icongroupinterna
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Systemic Lupus Erythematosus by Robert Lahita (Editor) (2003); ISBN: 0124339018; http://www.amazon.com/exec/obidos/ASIN/0124339018/icongroupinterna
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Systemic Lupus Erythematosus by Marian Wilkins Ropes, Marian N. Ropes; ISBN: 0674862554; http://www.amazon.com/exec/obidos/ASIN/0674862554/icongroupinterna
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Systemic Lupus Erythematosus by Peter A. Miescher (1995); ISBN: 3540590390; http://www.amazon.com/exec/obidos/ASIN/3540590390/icongroupinterna
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Systemic lupus erythematosus : a clinical analysis by James F. Fries; ISBN: 0721639178; http://www.amazon.com/exec/obidos/ASIN/0721639178/icongroupinterna
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Systemic Lupus Erythematosus and Sjogren's Syndrome: Pediatric and Heritable Disorders by Norman Talal, et al; ISBN: 1859220207; http://www.amazon.com/exec/obidos/ASIN/1859220207/icongroupinterna
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Systemic Lupus Erythematosus: Clinical and Experimental Aspects by J.S. Smolen, C.C. Zielinski; ISBN: 0387171541; http://www.amazon.com/exec/obidos/ASIN/0387171541/icongroupinterna
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Systemic Lupus Erythematosus: Pediatric and Heritable Disorders by Daniel J. Wallace (Editor) (1995); ISBN: 1859226469; http://www.amazon.com/exec/obidos/ASIN/1859226469/icongroupinterna
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Systemic Lupus Erythematosus: Proceedings of the International Symposium on Systemic Lupus Erythematosus Held November 24-25, 1978 by International Symposium on Systemic Lupus Erythematosus; ISBN: 0839116330; http://www.amazon.com/exec/obidos/ASIN/0839116330/icongroupinterna
Books 359
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Systemic Lupus Erythematosus: Renal Vasculitis (Contributions to Nephrology, Vol 99) by A. Sessa, et al (1992); ISBN: 3805556039; http://www.amazon.com/exec/obidos/ASIN/3805556039/icongroupinterna
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Systemic Lupus Erythematosus: The Wait For Lupus-Specific Treatments [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B0000AUH5Y; http://www.amazon.com/exec/obidos/ASIN/B0000AUH5Y/icongroupinterna
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Taking Charge of Lupus: How to Manage the Disease and Make the Most of Your Life by Maureen Pratt, et al (2002); ISBN: 0451206991; http://www.amazon.com/exec/obidos/ASIN/0451206991/icongroupinterna
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The 2002 Official Patient's Sourcebook on Lupus: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597833788; http://www.amazon.com/exec/obidos/ASIN/0597833788/icongroupinterna
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The Challenges of Lupus: Insights & Hope by Henrietta Aladjem, Henrietta Aladiem (1999); ISBN: 0895298813; http://www.amazon.com/exec/obidos/ASIN/0895298813/icongroupinterna
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The Clinical Management of Systemic Lupus Erythematosus by Peter H. Schur (Editor) (1996); ISBN: 0397514735; http://www.amazon.com/exec/obidos/ASIN/0397514735/icongroupinterna
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The First Year--Lupus: An Essential Guide for the Newly Diagnosed by Nancy C. Hanger (2003); ISBN: 1569245096; http://www.amazon.com/exec/obidos/ASIN/1569245096/icongroupinterna
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The Genetics of Systemic Lupus Erythematosus: Mapping of Susceptibility Loci for Human Sle (Comprehensive Summaries of Uppsala Dissertations, 878) by Anna-Karin B. Lindqvist (1999); ISBN: 9155445861; http://www.amazon.com/exec/obidos/ASIN/9155445861/icongroupinterna
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The Lupus Book: A Guide for Patients and Their Families by Daniel J. Wallace; ISBN: 0195132815; http://www.amazon.com/exec/obidos/ASIN/0195132815/icongroupinterna
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The Lupus Dog by Dexter Wright; ISBN: 0754113329; http://www.amazon.com/exec/obidos/ASIN/0754113329/icongroupinterna
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The Lupus Handbook for Women: Up-To-Date Information on Understanding and Managing the Disease Which Affects 1 in 500 Women by Carol Colman (Contributor), Robin, M.D. Dibner; ISBN: 0671790315; http://www.amazon.com/exec/obidos/ASIN/0671790315/icongroupinterna
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The Lupus Kid and Other Stories by Robert Wendell (Author) (2002); ISBN: 0595224164; http://www.amazon.com/exec/obidos/ASIN/0595224164/icongroupinterna
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The Official Patient's Sourcebook on Lupus Nephritis by James N. Parker, Icon Health Publications (2002); ISBN: 0597832242; http://www.amazon.com/exec/obidos/ASIN/0597832242/icongroupinterna
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Understanding Lupus/What It Is, How to Treat It and How to Cope With It by Henrietta Aladjem (1986); ISBN: 068418348X; http://www.amazon.com/exec/obidos/ASIN/068418348X/icongroupinterna
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What Your Doctor May Not Tell You About Autoimmune Disorders: The Revolutionary Drug-free Treatments for Thyroid Disease, Lupus, MS, IBD, Chronic Fati [DOWNLOAD: ADOBE READER] by Stephen B. Edelson, Deborah Mitchell
360 Lupus
(2003); ISBN: B00008SCEW; http://www.amazon.com/exec/obidos/ASIN/B00008SCEW/icongroupinterna •
What Your Doctor May Not Tell You About Autoimmune Disorders: The Revolutionary, Drug-Free Treatments for Thyroid Disease, Lupus, MS, IBD, Chronic Fatigue; Rheumatoid Arthritis, and Other Diseases by Stephen B./Mitchell Edelson (Author), et al (2003); ISBN: 0446679240; http://www.amazon.com/exec/obidos/ASIN/0446679240/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “lupus” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
[Beta] 1C-globulin and trypsin inhibitors in systemic lupus erythematosus and rheumatoid arthritis. Author: Lundh, Bengt.; Year: 1965; Lund, Gleerup, 1965
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Clinical and experimental studies on the hydralazine syndrome and its relationship to systemic lupus erythematosus. Author: Alarcón-Segovia, Donato.; Year: 1967; [Minneapolis] 1965
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Epidemiology and natural history of lupus vulgaris in Denmark, 1895-1954. Author: Horwitz, Ole.; Year: 1968; Copenhagen, Danish Tuberculosis Index, 1966
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Family studies in systemic lupus erythematosus. Author: Larsen, Rolf A.; Year: 2001; Oslo [distributed by Almqvist; Wiksell, Stockholm] 1972
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Immunopathogenesis of rheumatoid arthritis and systemic lupus erythematosus Author: Zvaifler, Nathan J.; Year: 1974; [Kalamazoo, Mich.]: Upjohn, 1974
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Lupus erythematosus: an immunohistochemical and clinical study of 485 patients Author: Faille-Kuyper, Eva Helena Baart de la.; Year: 1972; Utrecht: [s.n.], 1969
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Lupus erythematosus; a review of the current status of discoid and systemic lupus erythematosus and their variants. Author: Dubois, Edmund L.; Year: 1967; New York, McGraw-Hill [c1966]
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Serological profiles in Yersinia arthritis, rheumatoid arthritis and systemic lupus erythematosus defined by enzyme-linked immunosorbent assays Author: Gripenberg, Marianne.; Year: 1972; Helsinki: [s.n.], 1981; ISBN: 9519930035
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Systemic lupus erythematosus Author: Hughes, Graham R. V. (Graham Robert Vivian); Year: 1973; London; Philadelphia: Saunders, 1982
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The Clinical management of systemic lupus erythematosus Author: Schur, Peter H.; Year: 1973; New York: Grune; Stratton, c1983; ISBN: 0808915436
11
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
Books 361
http://www.amazon.com/exec/obidos/ASIN/0808915436/icongroupinterna •
The Gastrointestinal manifestations of systemic lupus erythematosus: a review of the literature Author: Hoffman, Bruce,; Year: 1976; New York: Grune; Stratton, 1980
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The kidney in systemic lupus erythematosus. Author: Rothfield, Naomi F.,; Year: 1972; Denver, National Kidney Foundation, 1972
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The problem of lupus vulgaris. Author: Aitken, Robert,; Year: 1974; Baltimore, Williams and Wilkins, 1946
Chapters on Lupus In order to find chapters that specifically relate to lupus, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and lupus using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “lupus” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on lupus: •
Systemic Lupus Erythematosus Adult Onset Source: in Maddison, P.J. et al., Eds. Oxford Textbook of Rheumatology. Volume 2. New York, NY: Oxford University Press, Inc. 1993. p. 733-755. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals presents an overview of systemic lupus erythematosus (SLE) in adults. Data on the epidemiology and natural history of SLE are provided. The clinical features of SLE are described, focusing on nonspecific features and musculoskeletal, dermatological, cardiovascular, pulmonary, renal, neurological, and hematological manifestations. Diseases complicating lupus are identified. Data on lupus during pregnancy, in males, and in the elderly are presented. The immunopathology of lupus is examined both in lupus-prone mouse strains and humans. This examination focuses on the specificity of autoantibodies in SLE, cellular abnormalities and cytokine dysregulation, and genetic factors with a role in susceptibility to SLE. General measures for treating lupus are outlined. Drug and other therapies used to treat SLE are described. 69 references, 8 figures, and 12 tables.
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Lupus in the Kidney and Urinary Tract Source: in Wallace, D.J. The Lupus Book: A Guide for Patients and Their Families. New York, NY: Oxford University Press. 1995. p. 139-145. Contact: Available from Lupus Foundation of America. 1300 Picard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. PRICE: $21.95 plus shipping. ISBN: 0195084438. Also available from Oxford University Press. Order Department, 2001 Evans Road, Cary, NC 27513. (800) 451-7556. Fax (919) 677-1303. Summary: This chapter on lupus in the kidney and urinary tract is from a handbook for patients and their families. After discussing the functional anatomy of the kidney, the author reviews the signs and symptoms of lupus nephritis. The author also presents a simple classification of kidney disease and an overview of therapeutic options. Lupus primarily affects the kidney glomerulus and produces a condition known as
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glomerulonephritis. Renal biopsy is performed to confirm a diagnosis of lupus nephritis and distinguish it from other diseases; to determine if the kidney tissue is inflamed, scarred, or both; and to evaluate treatment. In addition to glomerulonephritis, some kidney problems are caused by the drugs used to treat lupus, notably nonsteroidal antiinflammatory drugs (NSAIDs). High blood pressure should be managed aggressively, since it accelerates functional kidney impairment. Patients with renal disease should restrict their salt intake to no more than 3 grams a day; when renal function is 50 percent or less, normal protein intake should also be restricted. On the urinary tract side, the ureter is not involved in lupus, and the bladder is a rare target of the disease. But a condition known as lupus cystitis is observed in 1 to 5 percent of those with lupus. Young women are especially prone to developing urinary tract infections, and young women with lupus are particularly vulnerable to infections in general. The author cautions against the use of sulfa antibiotics in patients with lupus. (AA-M). •
Impact of Lupus upon the GI Tract and Liver Source: in Wallace, D.J. The Lupus Book: A Guide for Patients and Their Families. New York, NY: Oxford University Press. 1995. p. 128-138. Contact: Available from Lupus Foundation of America. 1300 Picard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. PRICE: $21.95 plus shipping. ISBN: 0195084438. Also available from Oxford University Press. Order Department, 2001 Evans Road, Cary, NC 27513. (800) 451-7556. Fax (919) 677-1303. PRICE: $25.00. Summary: This chapter on the impact of lupus on the gastrointestinal (GI) tract and the liver is from a guide for lupus patients and their families. The author first describes the basic anatomy and physiology of the GI tract, including the oral cavity, esophagus, stomach, intestines, and related organs including the liver, pancreas, and biliary tree (bile ducts and gallbladder). The author describes the impact of lupus through the use of brief case examples. Topics include reflux esophagitis, hiatal hernia, diagnostic tests, changes in bowel habits (diarrhea and or constipation), problems with nausea and vomiting, drug effects (notably from NSAIDs), peptic ulcer disease, the association of inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE), the problem of ascites (a collection of fluid in the abdominal cavity), malabsorption, and less common complications such as mesenteric vasculitis, infarction, and bowel hemorrhage. A separate section considers SLE-related liver diseases, including autoimmune (lupoid) hepatitis, enlargement of the liver, jaundice, hepatic vasculitis, Budd-Chiari syndrome, and ascites. The author concludes that difficulty in swallowing must be attended to immediately. Heartburn and acid indigestion can be brought on by medication, stress, or active lupus. Nonspecific bowel symptoms are common and can be managed symptomatically unless a fever, localized tenderness, swollen abdomen, or bloody stools are present. The liver can be involved in lupus because of reactions to medication, antiphospholipid antibiotics, or as a complication of infection. 1 figure.
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Lupus Erythematosus Source: in Bork, K., et al. Diseases of the Oral Mucosa and the Lips. Orlando, FL: W.B. Saunders Company. 1993. p. 212-216. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522 (individuals) or (800) 782-4479 (schools); Fax (800) 874-6418 or (407) 352-3445; http://www.wbsaunders.com. PRICE: $99.00 plus shipping and handling. ISBN: 0721640397.
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Summary: This chapter, from a textbook on diseases of the oral mucosa and the lips, discusses lupus erythematosus, a chronic autoimmune disease. Lupus erythematosus (LE) is classically divided into three subcategories: systemic lupus erythematosus (SLE) with multiorgan systemic disease; subacute cutaneous lupus erythematosus (SCLE), which primarily involves the skin; and discoid lupus erythematosus (DLE), in which disease is limited to the skin and mucous membranes. For each type, the authors describe the clinical features, oral features, and diagnosis, and present brief therapeutic recommendations. Full-color photographs illustrate the chapter; references are provided. 9 figures. 13 references. (AA-M). •
Course and Treatment of Lupus Nephritis Source: in Coggins, C.H. Hancock, E.W., Eds. Annual Review of Medicine: Selected Topics in the Clinical Sciences, Volume 45. Palo Alto, CA: Annual Reviews Inc. 1994. p. 525-537. Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax: (415) 855-9815. PRICE: $47. ISBN: 0824305450. Summary: This chapter, from an 'Annual Review of Medicine,' discusses the course and treatment of lupus nephritis. The authors note that renal involvement by systemic lupus is variable; some patients have minimal clinical and histologic involvement, whereas others have fulminant renal failure and severe proliferative renal lesions. The chapter focuses on the World Health Organization (WHO) classification system which defines six major patterns of renal involvement, each with characteristic clinical correlates and a typical course and prognosis. The WHO classification is advantageous because it uses light microscopy, immunofluorescence, and electron microscopy to classify glomerular involvement in systemic lupus erythematosus. The chapter discusses each of the six levels of the classification system and includes reproductions of light microscopy photographs for five of the six levels. 5 figures. 38 references. (AA-M).
Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to lupus have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 •
Asian Language: Sources of Health Materials Source: Washington, DC: Office of Minority Health Resource Center. 199x. [11 p.]. Contact: Available from Office of Minority Health Resource Center. P.O. Box 37337, Washington, DC 20013-7337. (800) 444-6472. Website: www.omhrc.gov. PRICE: Single copy free. Summary: This directory lists sources identified by the Office of Minority Health Resource Center (OMH RC) that produce or distribute health promotion materials in
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You will need to limit your search to “Directory” and “lupus” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “lupus” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.
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various Asian languages. Materials concentrate on minority health priority areas and associated risk factors: cancer, cardiovascular diseases and stroke, chemical dependency, diabetes, infant mortality, homicide, suicide, and unintentional injury. Sources of AIDS information and educational materials are also included. Topics related to kidney and urologic diseases include AIDS, cultural awareness, high blood pressure (hypertension), lupus, men's health, nutrition, sexually transmitted diseases, and women's health. Sources are arranged alphabetically. Organization entries include organization name, address, telephone number, source title, and annotation. The primary languages in which the organization provides materials are noted. Organizations should be contacted directly to determine the cost and availability of bulk quantities or for permission to photocopy.
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CHAPTER 8. MULTIMEDIA ON LUPUS Overview In this chapter, we show you how to keep current on multimedia sources of information on lupus. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on lupus is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “lupus” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “lupus” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on lupus: •
Lupus: When You Have Been Diagnosed Contact: Minnesota Chapter of the Lupus Foundation of America, Inc. Summary: This videorecording for individuals with lupus focuses on living with lupus. The videotape provides basic facts about lupus, identifies the symptoms of lupus, and presents comments from individuals with lupus and physicians who treat lupus patients. Topics discussed by lupus sufferers include their feelings upon being diagnosed with lupus; the types of illnesses they were told they had prior to their lupus diagnosis; the problems caused by not looking sick; factors to consider in finding the right doctor; the effects of treatment, particularly prednisone; the ways they take care of themselves; the effect of the disease on their relationships with others, including spouses, other family members, and friends; the impact of the disease on child bearing and child rearing; the lessons they have learned from having a chronic disease; and the importance of participating in a support group and contacting the Lupus Foundation for information. Participating physicians commented on the diagnosis and treatment of lupus, their interactions with patients, and the activities they suggest to promote the health of lupus patients.
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Stories of Lupus Source: Mosaic Productions, LLC. 1999. (VHS videocassette). Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 toll-free or (301) 670-9292. Website: www.lupus.org/lupus. PRICE: $14.95 plus shipping and handling; bulk discount available. Summary: This videotape for people who have lupus is a documentary in the journalistic style of CBS newsman Charles Kuralt, who died of complications of lupus. Two people newly diagnosed with this complex autoimmune disease interview a diverse group of people living with lupus. These interviews reveal the mysterious nature of the disease and recount the journey toward wellness and acceptance of a life threatening chronic illness. Narrative by Charles Osgood provides information on lupus and serves as an introduction to the interview segments.
Bibliography: Multimedia on Lupus The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in lupus (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on lupus: •
Drug-induced systemic lupus erythematosus [videorecording] Source: Dept. of Medicine, Emory University, School of Medicine; Year: 1978; Format: Videorecording; Atlanta: Georgia Regional Medical Television Network: [for loan and sale by A. W. Calhoun Medical Library], 1978
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Lupas [i.e. lupus] subsets as manifested in dermatologic disease [videorecording] Source: [presented by] the Marshfield Regional Video Network, in cooperation with Marshfield Clinic & St. Joseph's Hospital; Year: 1981; Format: I.e. lupus; Marshfield, WI: The Network, 1981
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Lupus: wolf in disguise [videorecording] Source: Los Angeles County Medical Association; produced by Dave Bell Associates; Year: 1974; Format: Videorecording; Garden Grove, Ca.: Trainex, 1974
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Lupus erythematosus, collagen-vascular diseases, and eczema [videorecording] Source: Dept. of Medicine, Emory University, School of Medicine; Year: 1979; Format: Videorecording; Atlanta: Emory Medical Television Network: [for loan and sale by A. W. Calhoun Medical Library, 1979]
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Lupus-- insights, emotions, encouragements [videorecording] Source: written and produced by William & Estelle Gill, in cooperation with the Lupus Foundation of America, Inc., Marcy Zitron Chapter, Columbus, Ohio; Year: 1993; Format: Videorecording; Columbus, Ohio: Production House; Media, PA: Media Inc., c1993
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Mechanisms of autoimmunity and systemic lupus erythematosus [videorecording] Source: with Bruce N. Cronstein; Year: 1988; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1988
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Systemic lupus [sound recording] Source: produced by Audio Master; Year: 1988; Format: Sound recording; [Atlanta, Ga.]: American Rheumatism Association, [1988]
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Systemic lupus erythematosis [videorecording] Source: presented by the Department of Pediatrics, Emory University, School of Medicine; Year: 1984; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1984
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Systemic lupus erythematosus (SLE) [videorecording]: it means some changes Source: Biomedical Media Production Unit, the University of Michigan Medical Center, Office of Educational Resources & Research; Year: 1981; Format: Videorecording; Ann Arbor, Mich.: University of Michigan, c1981
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Systemic lupus erythematosus [slide] Source: Ellen M. Ginzler; Year: 1979; Format: Slide; [New York]: Medcom, c1979
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The Treatment of lupus [videorecording] Source: presented by the Department of Medicine, Emory University, School of Medicine; Year: 1985; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1985
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Voices of lupus [videorecording] Source: [presented by] Films for the Humanities & Sciences, the Wolf Pack and the Hospital for Special Surgery; a Harriet Fier & Stephen Mantell Production; Year: 1992; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1992
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CHAPTER 9. PERIODICALS AND NEWS ON LUPUS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover lupus.
News Services and Press Releases One of the simplest ways of tracking press releases on lupus is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “lupus” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to lupus. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “lupus” (or synonyms). The following was recently listed in this archive for lupus: •
Autoantibodies precede the clinical onset of systemic lupus erythematosus Source: Reuters Medical News Date: October 16, 2003
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Smoking may exacerbate lupus: study Source: Reuters Health eLine Date: June 24, 2003
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La Jolla to file for U.S. approval of Riquent lupus drug Source: Reuters Industry Breifing Date: May 05, 2003
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Infliximab may induce antinuclear antibodies, but does not increase lupus risk Source: Reuters Medical News Date: April 22, 2003
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FDA fast tracks Human Genome's B-lymphocyte compound for lupus Source: Reuters Industry Breifing Date: April 21, 2003
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Fish oil supplementation appears to reduce lupus activity Source: Reuters Industry Breifing Date: March 11, 2003
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Fish oil may ease symptoms of lupus: study Source: Reuters Health eLine Date: March 11, 2003
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La Jolla stock collapses on failed phase III trial of lupus drug Source: Reuters Industry Breifing Date: February 18, 2003
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La Jolla reports failure of lupus drug in phase III trial Source: Reuters Medical News Date: February 18, 2003
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Chemo without stem cell transplant treats lupus Source: Reuters Health eLine Date: January 10, 2003
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EU begins review of Genelabs lupus drug Source: Reuters Industry Breifing Date: January 09, 2003
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Genelabs submits lupus treatment to EU regulators Source: Reuters Industry Breifing Date: December 23, 2002
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Genelabs submits phase III lupus study protocol to FDA Source: Reuters Industry Breifing Date: November 15, 2002
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Variant of PDCD1 gene associated with susceptibility to lupus Source: Reuters Medical News Date: October 28, 2002
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Gene variant may up lupus risk Source: Reuters Health eLine Date: October 28, 2002
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Low-dose cyclophosphamide regimen shown effective for lupus nephritis Source: Reuters Industry Breifing Date: September 24, 2002
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Genelabs, Patheon in lupus-drug deal Source: Reuters Industry Breifing Date: September 19, 2002
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Genelabs lupus drug approvable pending new trial; firm's shares soar Source: Reuters Industry Breifing Date: August 30, 2002
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FDA okays Fred Hutchinson Center lupus test Source: Reuters Industry Breifing Date: August 28, 2002
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FDA approves Fred Hutchinson Center lupus test Source: Reuters Medical News Date: August 28, 2002
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Genelabs can seek EU-wide approval for lupus drug Source: Reuters Industry Breifing Date: June 20, 2002
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Antibodies identify fetal heart block risk in expectant mothers with lupus Source: Reuters Medical News Date: June 13, 2002
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Genelabs expects FDA decision on Lupus drug by August Source: Reuters Industry Breifing Date: May 29, 2002
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Study finds "unexpected" steroid levels in pregnant lupus patients Source: Reuters Medical News Date: May 17, 2002
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Sharp rise in lupus deaths noted among black women Source: Reuters Health eLine Date: May 02, 2002
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Key proteins linked to pregnancy loss in lupus Source: Reuters Health eLine Date: February 26, 2002
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B-lymphocyte superantigen-based therapy under investigation for lupus Source: Reuters Industry Breifing Date: February 26, 2002
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Interferon-inducible genes a new potential target in lupus Source: Reuters Medical News Date: February 25, 2002
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Etanercept use linked to systemic lupus erythematosus Source: Reuters Industry Breifing Date: February 15, 2002
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Arthritis drug linked to rare lupus side effect Source: Reuters Health eLine Date: February 15, 2002
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Hispanics may be at increased risk of early lupus damage Source: Reuters Medical News Date: January 10, 2002
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Smoking linked to development of systemic lupus erythematosus Source: Reuters Medical News Date: December 31, 2001
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Smoking ups lupus risk: report Source: Reuters Health eLine Date: December 20, 2001
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La Jolla lupus drug receives European orphan drug designation Source: Reuters Industry Breifing Date: November 28, 2001
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Interferon-alpha may play key role in lupus autoimmunity Source: Reuters Medical News Date: November 16, 2001
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Study suggests potential new way to treat lupus Source: Reuters Health eLine Date: November 15, 2001
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Traditional Framingham factors do not explain increased risk of CVD in lupus Source: Reuters Medical News Date: November 14, 2001
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La Jolla presents results of phase II/III trial of lupus drug Source: Reuters Industry Breifing Date: November 14, 2001
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Human Genome Sciences to initiate phase I study for the treatment of lupus Source: Reuters Industry Breifing Date: November 01, 2001
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Scientists learn how lupus destroys nervous system Source: Reuters Health eLine Date: October 31, 2001
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Distinct risk factors identify lupus patients at risk of cardiovascular disease Source: Reuters Medical News Date: October 19, 2001
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Interferon-inducible lfi202 implicated as candidate gene for lupus Source: Reuters Medical News Date: September 26, 2001
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Oral cyclophosphamide may have advantages in severe lupus nephritis Source: Reuters Industry Breifing Date: August 20, 2001
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FDA issues 'not approvable' letter on Genelabs, Watson lupus drug Source: Reuters Industry Breifing Date: June 27, 2001
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Lupus nephritis may be mediated by molecular mimicry Source: Reuters Medical News Date: May 16, 2001
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Aortic stiffness may be early sign of CHD in women with lupus Source: Reuters Medical News Date: May 01, 2001
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Headaches not part of lupus disease spectrum Source: Reuters Medical News Date: April 27, 2001
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Fearing deadlock, FDA panel defers vote on Genelabs' lupus drug Source: Reuters Industry Breifing Date: April 19, 2001
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Lupus patients should be evaluated for migraine Source: Reuters Medical News Date: April 11, 2001
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Anti-C1q antibodies are associated with lupus nephritis activity Source: Reuters Medical News Date: March 30, 2001 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “lupus” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “lupus” (or synonyms). If you know the name of a company that is relevant to lupus, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.
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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “lupus” (or synonyms).
Newsletters on Lupus Find newsletters on lupus using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “lupus.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “lupus” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •
Drug-Induced Rheumatic Syndromes Source: Bulletin on the Rheumatic Diseases. 51(4): 1-4. 2002. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (800) 268-6942 or (404) 872-7100. Fax (404) 872-9559. Website: www.arthritis.org. Summary: This newsletter provides health professionals with information on drug induced rheumatic syndromes. Categories of drug induced rheumatic diseases are drug induced lupus (DIL), drug induced myopathy/myositis (DIM), and drug induced vasculitis (DIV). Although more than 100 drugs have been implicated in DIL, the drugs most studied have been procainamide and hydralazine. However, these drugs are not commonly prescribed today, and the illness they produce is often different from those recently implicated in DIL. Minocycline is a treatment used for acne and rheumatoid arthritis that has caused immune and autoimmune phenomena. Several of the new recombinant biologics have been implicated in DIL, including interferon alpha, interferon gamma, and antitumor necrosis factor therapies. It is not possible to predict who will develop DIL, so patients with idiopathic lupus should be allowed to take potentially lupus inducing drugs but with careful monitoring. Drugs associated with the development of DIV include hematopoietic growth factors such as G-CSF and GMCSF; vaccines for hepatitis B, influenza, and others; and leukotriene inhibitors. The article concludes that the number of drugs that are capable of inducing rheumatic syndromes is growing. Elements in the assessment of a possible association between exposure and the development of a rheumatic disorder include temporal association, lack of likely alternative explanations, rechallenge, and biological plausibility. 1 table and 23 references.
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “lupus” (or synonyms) into
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the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on lupus: •
Sicca Syndrome and Sjogren's Syndrome in Lupus Source: Lupus News. 23(1): 14-18. Spring 2003. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article discusses sicca syndrome and Sjogren's syndrome, two syndromes that cause dryness in the eyes and mouth and are common to patients with lupus. Sicca syndrome is very common in the general population as well as in patients with connective tissue disorders and is often caused by Sjogren's syndrome, a chronic autoimmune disorder in which immune cells attack and destroy the glands that produce tears. Other conditions that may cause sicca syndrome include side effects from medications, low humidity environments, dehydration, and surface irritants. The chronic dry mouth caused by Sjogren's syndrome may cause dental caries, periodontal disease, oral candidiasis, mouth pain, halitosis, and difficulty swallowing. Complications of dry eyes caused by Sjogren's syndrome include a gritty feeling in the eye, blurred vision, infection, corneal abrasions and ulcerations, and vision loss. Other systemic complications may occur in Sjogren's syndrome but not sicca syndrome. Patients may relieve dry mouth symptoms by sipping water, stimulating the salivary glands, using artificial saliva, and maintaining a high level of dental hygiene. Treatments for dry eyes include artificial tears, ophthalmic ointments, and punctal occlusion. Precautions for laser vision correction, which may cause temporary dryness in the eyes, are listed. Other complications of sicca syndrome are dry skin, vaginal dryness, and a dry cough. Prescription medicines are available for patients with severe sicca symptoms. Side effects include sweating, nausea, and diarrhea. Immune suppression therapy is used only in cases of Sjogren's syndrome with severe autoimmune manifestations. 2 tables.
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Herbal Medicine and Lupus Source: Lupus News. 21(4): 1,4-5. Winter 2001. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article discusses the use of herbal medicines by patients with lupus to treat their condition. No herbal medicines have been proven effective in treating lupus. Echinacea, thought to be effective in treating upper respiratory tract ailments, has caused kidney problems and lupus flares in patients with lupus. Thundergod vine, sometimes helpful in improving joint tenderness in patients with rheumatoid arthritis, has caused rashes, gastrointestinal problems, and menstrual irregularities in patients with lupus. Wild yams, containing DHEA, a weak male hormone, is thought to modify immune response. A study in which lupus patients took DHEA in a purified form did result in modest improvement in lupus symptoms. Patients with lupus should discuss using alternative therapies and herbal supplements with their rheumatologist. 14 references.
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Benefits of Exercise in Patients With Lupus Source: Lupus Foundation Network. 2-3; Winter 1997. Contact: Lupus Foundation of Greater Washington, 515 A Braddock Road, Alexandria, VA 22314. (703) 684-2925. Summary: This newsletter article for health professionals discusses the benefits of regular, appropriate exercise in the management of symptoms associated with lupus. Exercise relieves stiffness, maintains or increases joint flexibility, and keeps bones strong. Strength training protects the body against injuries by promoting proper posture and balance. Aerobic exercise improves cardiovascular fitness. In addition, exercise triggers the release of endorphins in the brain, which promotes a feeling of well-being; improves sleep quality; and reduces stress. Individuals with lupus must strike a balance between rest and exercise, however, so the best approach for many patients is to gradually introduce exercise. Recommended exercises for patients with mild lupus are presented, and the need to tailor and modify an exercise program for each patient is discussed.
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Vasculitis and Systemic Lupus Erythematosus Source: SLE Newsletter. 20(4):5; Winter 1997/1998. Contact: Bay Area Lupus Foundation, Inc., 2635 North First Street, Suite 206, San Jose, CA 95134. (408) 954-8600. Summary: This newsletter article for individuals with lupus presents an overview of vasculitis, which is an inflammation of both large and small blood vessels. It describes the clinical features of vasculitis, including raised red or purplish skin lesions on the fingertips, forearms, elbows, and toes; infarcts at the nailfold; urticaria; bluish discoloration of the fingers and toes; pain from poor circulation; an absent pulse in a digit; abdominal pain; or blood in the bowel. In addition, the article discusses the diagnosis and treatment of vasculitis.
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How Systemic Lupus Erythematosus Affects the Blood Source: Lupus Letter. 1(2):3; 1996. Contact: Available from Lupus Foundation of america, National Office, 4 Research Place, Suite 180, Rockville, MD 20850-3226. (301) 670-9292. (800) 558-0121. Summary: This newsletter article for lupus patients uses a question and answer format to explain how systemic lupus erythematosus (SLE) affects the blood. Types of blood cells and their functions are identified. Common blood cell conditions that occur in individuals with SLE are highlighted, including anemia, thrombocytopenia, and leukopenia. In addition, the causes of these conditions are presented.
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An Infamous Battle: The Sun vs. Lupus Source: Lupus News. 16(2):14-15. 1996. Contact: Available from Lupus Foundation of America. 1330 Piccard Drive, Suite 200, Rockville, MD 20850. (800) 558-0121 or (301) 670-9292. Website: www/lupus.org/lupus. Summary: This newsletter article for physicians and dermatologists discusses the ways in which sun exposure can be harmful to lupus patients. It indicates that sun exposure may worsen lupus skin lesions and can cause skin cancer at sites of chronic lupus skin lesions. Both UV-A and UV-B (ultraviolet wavelengths of the sun) can be harmful, but
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complete avoidance and protection against UV-A is particularly difficult. Patients with lupus are advised to avoid sunbathing, wear adequate protective clothing, avoid the outdoors between 10 a.m. and 3 p.m., avoid surfaces that reflect substantial ultraviolet light such as sand and snow, and wear sunscreen on exposed skin everyday. Additionally, those patients with light spots on the skin at sites that have had lupus skin lesions are recommended to use thick cosmetics such as Dermablen or Covermark to provide some sun protection while also camouflaging irregular pigment or scars. •
Systemic Lupus Erythematosus: Women's Health Issues Source: Bulletin on the Rheumatic Diseases. 49(8): 1-3. 2001. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (404) 872-7100. Fax (404) 872-9559. Summary: This newsletter article provides health professionals with information on systemic lupus erythematosus (SLE) in relation to issues specific to women's health, including pregnancy, contraception, fertility, sexuality, management of menopause, osteoporosis, coronary artery disease, and chronic fatigue. Pregnancy is high risk for both the woman with SLE and her fetus. Pregnant women with SLE are at higher risk for both preeclampsia and premature membrane rupture. Fetal problems associated with SLE include preterm birth, intrauterine growth retardation, placental insufficiency, pregnancy loss, and congenital heart block. Although barrier contraception is the safest method in SLE, other options include oral contraceptives, the intrauterine device, and tubal ligation. Fertility is usually not a problem in women with SLE, but some SLE treatment regimens, such as monthly pulse intravenous cyclophosphamide, put fertility at risk. Women with SLE may face sexuality issues because their body image is affected both by the disease and by its treatment. More women with SLE are reaching menopause, and studies have suggested that estrogen replacement therapy does not increase SLE flares. Both premenopausal and postmenopausal women with SLE are at risk for osteoporosis because of the use of prednisone. The major cause of death in women with SLE is cardiovascular disease, so they should be considered as candidates for screening for early atherosclerosis. Chronic fatigue is a major complaint of women with SLE. 4 tables and 18 references.
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Men With Lupus and Antiphospholipid Syndrome Source: Minnesota Lupus News. 22(2): 3-4. April-May 1998. Contact: Available from Minnesota Chapter, Lupus Foundation of America, Inc. International Market Square, 275 Market Street, Suite C19, Minneapolis, MN 55405-1620. (800) 645-1131 or (612) 375-1131. Summary: This newsletter article provides men with lupus and antiphospholipid antibody syndrome with information on these conditions. Men are usually not the focus of such articles because most of what is known about gender differences in lupus or in antiphospholipid antibody syndrome is not very dramatic. Studies have found that men with lupus may have more problems with blood platelets, blood vessel blockage, and lung scarring than women. There has been speculation about the role of male characteristics, and specific measures of hormone levels in men with lupus have given conflicting results. However, in measures that they and their families can make, men with lupus and antiphospholipid antibody syndrome have normal beards, voices, hair patterns, muscles, and other male characteristics, as well as normal sexual drive and performance. The use of hormones to treat these conditions in men has not been significantly researched. The prognosis is about the same for men and women.
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Autoimmune Thyroid Disorders and Systemic Lupus Source: Lupus News. 22(1): 15-18. Spring 2002. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article provides people who have lupus with information on autoimmune thyroid disorders (AITDs) and systemic lupus erythematosus (SLE). AITDs are a group of common medical problems that involve antibody reactions against the thyroid gland. The thyroid may become either underactive or overactive. Although AITD and SLE coexist with more frequency than would be expected by chance, there are no specific guidelines to testing for AITD in patients with SLE or other autoimmune rheumatologic disorders. Test results can be difficult to interpret when a patient is ill from any cause. For example, lupus flare, infections, and fasting will modify the thyroid hormone tests without necessarily meaning that there is true thyroid disease. A test for thyroid stimulating hormone (TSH) levels is a good screening method for minor or early thyroid gland dysfunction. However, in many cases, thyroid treatment should not be initiated unless a complete set of thyroid function tests is conducted. The article describes the symptoms of Graves' disease (overactive thyroid) and Hashimoto's thyroiditis (underactive thyroid) and discusses the overlap of these disorders. The article recommends that physicians consider screening patients with lupus and other autoimmune disorders for AITD every 2 to 3 years using a serum TSH measurement. 1 figure and 5 references.
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Lupus and the Young Adult Source: Minnesota Lupus News. 23(5): 1,4,9. October/November 1999. Contact: Available from Minnesota Chapter, Lupus Foundation of America, Inc. International Market Square, 275 Market Street, Suite C19, Minneapolis, MN 55405-1620. (800) 645-1131 or (612) 375-1131. Summary: This newsletter article provides young adults who have lupus with information on the impact of this disease on areas such as education, dating, marriage, and parenthood. Often young adults are in college or graduate school, or are continuing their studies in some way, and lupus can create difficulties in completing educational plans. Learning to be flexible and communicating with professors will help young adults complete their education. Lupus can also create the need for adjustments and serious compromises in the areas of dating and marriage. Couples must realize that lupus is a lifelong illness and will permanently change the dynamic of their relationship in both positive and negative ways. Being a parent with lupus is made easier by being organized and flexible, having a strong support system, and talking with one's children about lupus in terms they can understand.
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Lupus and Pregnancy: Can They Go Together? Source: Lupus News. 20(5): 8-11. Winter 2000. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article uses a question and answer format to provide women who have lupus with information on managing a pregnancy. Lupus is more common
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among women than men, and it is often diagnosed during the childbearing years. Therefore, women with lupus are faced with the difficult decision of whether or not to become pregnant. Most women who have lupus can have successful pregnancies. One of the most common questions women who have lupus ask is how pregnancy will affect their lupus. Although recent studies show that lupus flares are common in pregnancy, most are mild or moderate and are manageable. Women who have lupus nephritis appear to be at more risk during pregnancy than women without kidney disease, and recent studies support this observation. However, most women with lupus nephritis, particularly women with well controlled lupus nephritis, have a satisfactory pregnancy outcome. Another issue of concern to women with lupus is how it will affect them and their baby during pregnancy. Pregnancy loss is one complication. Women who have antiphospholipid syndrome are at particular risk for pregnancy loss. Preeclampsia is a common complication in all pregnancies, but some patients with lupus are at greater risk for this complication than others, including women using steroids, women with kidney damage, and women with lupus nephritis. Other complications that women or their baby may experience include preterm birth, fetal growth impairment, and neonatal lupus erythematosus. Women with lupus may also be concerned about the effect of the drugs used to treat lupus on their pregnancy. Drugs that may safely be used to treat lupus during pregnancy are glucocorticoids. A final issue of concern to women with lupus is prenatal care. The article offers guidelines for prepregnancy, prenatal, and postnatal care and care during labor and delivery. •
Musculoskeletal Aspects of Systemic Lupus Erythematosus (SLE) -Part 2 Source: Lupus News. 19(4): 10-11. Fall 1999. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article, the second of two parts, provides health professionals with information on the musculoskeletal aspects of systemic lupus erythematosus (SLE). Besides arthritis, osteonecrosis is the other major skeletal problem in SLE. Osteonecrosis involves the death of bone as a result of loss of blood flow, followed by death of all other cellular elements. The condition has four pathological stages. Imaging studies are used to clinically detect osteonecrosis, and five radiologic stages have been established. Although the cause of osteonecrosis in people who have SLE is unknown, the use of high doses of glucocorticosteroids may have a role in its etiology. Other hypothesized but unproven potential factors include an increased tendency for blood clots, fatty emboli, increased pressure inside the joint capsule, increased bone marrow pressure, and swelling inside the bone cavity. Although any joint may be involved, the femoral head is the most common location for osteonecrosis, making the hip the most commonly involved joint. The most commonly recommended procedure to treat osteonecrosis of the femoral head is decompression of the femoral head. Joint replacement is also another option. Fibromyalgia and osteoporosis are two conditions that may co-occur with SLE.
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Complex Genetic Basis of Systemic Lupus Erythematosus-Part 1, The Source: Lupus News. 19(4): 12-13. Fall 1999. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus.
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Summary: This newsletter letter, the first of two parts, provides people who have systemic lupus erythematosus (SLE) with information on the genetic basis of SLE. The inheritance patterns of SLE are complex and the precise genes involved in the genetic susceptibility may vary from population to population. Not only is the prevalence of SLE different in different populations, but the natural history of the disease is different in different populations. This is consistent with the belief that different combinations of genes play a role in the genetic susceptibility in different populations. Studies in which more than one family member is affected with SLE are being conducted to try to directly identify the genes involved in SLE. When many families are studied, specific regions of the chromosomes can be identified as being involved on a population basis. As a result of such family studies, more than 100 genes now are thought to be involved in the genetic susceptibility of SLE. Although specific genes are sometimes identified through family studies, other types of studies are performed to look for the specific gene within an identified region. •
Early Recognition of Systemic Lupus Erythematosus Source: Lupus Journal. p. 1-4. 1995. Contact: Available from Maryland Lupus Foundation. 7400 York Road, Baltimore, MD 21204. (410) 337-9000. Summary: This special publication, prepared by the Maryland Lupus Foundation, presents the latest information on the recognition and diagnosis of systemic lupus erythematosus (SLE). Topics include the importance of early recognition of SLE; guidelines for laboratory testing and criteria for SLE classification; symptoms, including rashes, mucous membrane involvement, Raynaud's syndrome, serositis, heart and lung involvement, and the affect of SLE on the renal and neurologic systems; and the role of laboratory tests to confirm the clinical impression, particularly autoantibody tests. The author notes that glomerulonephritis and nephrotic syndrome are the most common renal disorders seen. The author also reiterates that in this disorder, more than any other, the presenting clinical pattern can be dramatically variable both for a specific individual and the population in general. 1 figure.
Academic Periodicals covering Lupus Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to lupus. In addition to these sources, you can search for articles covering lupus that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for lupus. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with lupus. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The following
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drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to lupus: Azathioprine •
Systemic - U.S. Brands: Imuran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202077.html
Chloroquine •
Systemic - U.S. Brands: Aralen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202133.html
Cyclophosphamide •
Systemic - U.S. Brands: Cytoxan; Neosar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202174.html
Hydroxychloroquine •
Systemic - U.S. Brands: Plaquenil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202288.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
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Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to lupus by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “lupus” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for lupus: •
Abetimus http://www.rarediseases.org/nord/search/nodd_full?code=1051
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Abetimus http://www.rarediseases.org/nord/search/nodd_full?code=1052
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Monoclonal antibody for immunization against lupus http://www.rarediseases.org/nord/search/nodd_full?code=139
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Dehydroepiandrosterone http://www.rarediseases.org/nord/search/nodd_full?code=458
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NAPA of the Bahamas http://www.rarediseases.org/nord/search/nodd_full?code=823
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Bindarit http://www.rarediseases.org/nord/search/nodd_full?code=904
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Recombinant humanized monoclonal antibody 5c8 http://www.rarediseases.org/nord/search/nodd_full?code=906
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Humanized MAb (IDEC-131) to CD40L http://www.rarediseases.org/nord/search/nodd_full?code=966
If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.14 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:15 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
14
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 15 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “lupus” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “lupus” (or synonyms) into the “For these words:” box. The following is a sample result: •
Renal Insufficiency and Failure Associated with Immune Globulin Intravenous Therapy: United States, 1985-1998 Source: MMWR. Morbidity and Mortality Weekly Report. 48(24): 518-521. June 25, 1999. Contact: Available from Superintendent of Documents, U.S. Government Printing Office. Washington, DC 20402. (202) 512-1800. Available for free in electronic format on the World Wide Web at www.cdc.gov or from CDC's file transfer protocol server at ftp.cdc.gov. Summary: Immune globulin intravenous (IGIV) is an immunoglobulin G preparation made from pooled human plasma stabilized with glucose, maltose, glycine, sucrose, sorbitol, or albumin and is used as prophylaxis or therapy for various medical disorders. This article from the Morbidity and Mortality Weekly Report of the CDC reports on renal insufficiency and failure associated with IGIV therapy in the United States between 1985 and 1998. During this time period, the Food and Drug Administration (FDA) received approximately 120 reports worldwide of renal adverse events (RAEs) (i.e., acute kidney failure or insufficiency) following IGIV administration. This report describes the epidemiology of IGIV associated RAEs in the United States and emphasizes the importance of reviewing indications for IGIV use and implementing precautions during its administration. Among the 88 case patients reported in the United States, the media age was 60.5 years and 48 (55 percent) were male. Of the 54 case patients that were reported with conditions associated with acute renal failure, 35 (65 percent) were aged greater than 65 years, 30 (56 percent) had diabetes mellitus, and 14 (26 percent) had prior renal insufficiency. Indications for IGIV use were reported in 85 (97 percent) case patients and included 39 (46 percent) hematologic, 20 (23 percent) immunologic, 17 (20 percent) neurologic, and 9 (11 percent) infectious diseases. Seventy nine (90 percent) case patients received sucrose containing IGIV products, seven received IGIV with maltose or glucose, and two received IGIV in which the stabilizer was undetermined. Approximately 35 (40 percent) patients had severe symptoms requiring dialysis; no significant differences in baseline serum creatinines or other underlying risk factors were found between patients requiring and not requiring dialysis. The mean recovery time of renal function, with or without dialysis, was 10 days after RAE onset; however, 13 (15 percent) of the 88 patients died despite therapy. These patients had severe underlying conditions (i.e., cardiac insufficiency, pneumonia, or
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systemic lupus erythematosis), and the extent to which RAEs contributed to their deaths was undetermined. Appended to the article is a lengthy editorial note in which the editor comments on the report and emphasizes the importance of monitoring patients, particularly high risk patients, on IGIV preparations. 1 table. 6 references.
The NLM Gateway16 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “lupus” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 43217 340 62 63 1 43683
HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.20 Simply search by “lupus” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
16
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
17
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 18 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 19 20
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists21 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.22 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Lupus In the following section, we will discuss databases and references which relate to the Genome Project and lupus. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).24 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 21 Adapted 22
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 23 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 24 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “lupus” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for lupus: •
Lupus Erythematosus, Systemic Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?152700
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Systemic Lupus Erythematosus with Hemolytic Anemia, Susceptibility To, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607279
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Systemic Lupus Erythematosus with Nephritis, Susceptibility To, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607965
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Systemic Lupus Erythematosus with Nephritis, Susceptibility To, 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607966
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Systemic Lupus Erythematosus with Nephritis, Susceptibility To, 3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?607967
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Systemic Lupus Erythematosus, Susceptibility To, 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601744
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Systemic Lupus Erythematosus, Susceptibility To, 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605218
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Systemic Lupus Erythematosus, Susceptibility To, 3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605480
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Systemic Lupus Erythematosus, Vitiligo-related Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?606579 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “lupus” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will 25
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 26 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “lupus” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on lupus can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to lupus. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to lupus. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “lupus”:
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Guides on lupus Lupus http://www.nlm.nih.gov/medlineplus/lupus.html
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Other guides Autoimmune Diseases http://www.nlm.nih.gov/medlineplus/autoimmunediseases.html Kidney Diseases http://www.nlm.nih.gov/medlineplus/kidneydiseases.html Myositis http://www.nlm.nih.gov/medlineplus/myositis.html Sjogren's Syndrome http://www.nlm.nih.gov/medlineplus/sjogrenssyndrome.html
Within the health topic page dedicated to lupus, the following was listed: •
General/Overviews Do I Have Lupus? http://www.niams.nih.gov/hi/topics/lupus/tengo/english.htm Frequently Asked Questions About Lupus Source: Lupus Foundation of America http://www.lupus.org/education/faq.html Lupus http://www.nlm.nih.gov/medlineplus/tutorials/lupusloader.html Lupus Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00115 Lupus/Systemic Lupus Erythematosus (SLE) Source: Arthritis Foundation http://www.arthritis.org/conditions/DiseaseCenter/lupus.asp
•
Diagnosis/Symptoms Antinuclear Antibody Test Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/ana/test.html Laboratory Tests Used in the Diagnosis of Lupus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/labtests.html
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Treatment 2003 Drug Guide Source: Arthritis Foundation http://www.arthritis.org/conditions/DrugGuide/default.asp
Patient Resources 399
Anti-Malarials in the Treatment of Lupus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/antimalarials01.html Azathioprine Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/lupus/lupusguide/chppis15.htm Cyclophosphamide Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/lupus/lupusguide/chppis16.htm Immune Suppressants and Related Drugs Used for Lupus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/immune.html Medications Source: Lupus Foundation of America http://www.lupus.org/education/brochures/medications.html Nonsteroidal Anti-Inflammatory Drugs (NSAIDS) Source: Lupus Foundation of America http://www.lupus.org/education/brochures/nsaid.html Steroids in the Treatment of Lupus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/steroids.html •
Nutrition Nutrition and Lupus Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/lupus/lupusguide/chppis9.htm
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Coping Depression in Lupus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/depress07.html Living with Lupus http://www.niams.nih.gov/hi/topics/lupus/lupusguide/luppdf/livingwl.pdf Sexuality and Lupus http://www.niams.nih.gov/hi/topics/lupus/lupusguide/luppdf/sexualty.pdf
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Specific Conditions/Aspects Antiphospholipid Antibodies: Anticardiolipin Antibodies and the Lupus Anticoagulant in Systemic Lupus Erythematosus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/antiphos02.html Blood Disorders in Lupus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/blood04.html
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Cardiopulmonary Disease and Lupus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/cardio05.html Drug-Induced Lupus Erythematosus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/drug.html Joint and Muscle Pain in Systemic Lupus Erythematosus (SLE) Source: Lupus Foundation of America http://www.lupus.org/education/brochures/jointpain.html Joint Function and Lupus http://www.niams.nih.gov/hi/topics/lupus/lupusguide/luppdf/jointfun.pdf Kidney Disease and Lupus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/kidney.html Lupus and Infections and Immunizations Source: Lupus Foundation of America http://www.lupus.org/education/brochures/infections.html Lupus and Vasculitis Source: Lupus Foundation of America http://www.lupus.org/education/brochures/vasculitis.html Many Shades of Lupus: Information for Multicultural Communities Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/lupus/shades/index.htm Serious Conditions Associated With Lupus Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/lupus/lupusguide/chppis5.htm Skin Care and Lupus http://www.niams.nih.gov/hi/topics/lupus/lupusguide/luppdf/skincare.pdf Skin Disease in Lupus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/skindisease.html Systemic Lupus and the Nervous System Source: Lupus Foundation of America http://www.lupus.org/education/brochures/systemic.html What People with Lupus Need to Know About Osteoporosis Source: Osteoporosis and Related Bone Diseases-National Resource Center http://www.osteo.org/newfile.asp?doc=r801i&doctitle=What%2BPeople%2Bwith %2BLupus%2BNeed%2Bto%2BKnow%2BAbout%2BOsteoporosis&doctype=HTML %2BFact%2BSheet •
Children Childhood Lupus Source: Lupus Foundation of America http://www.lupus.org/education/brochures/child06.html
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Living with Lupus Source: Nemours Foundation http://kidshealth.org/parent/medical/arthritis/lupus.html •
From the National Institutes of Health Systemic Lupus Erythematosus Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/lupus/slehandout/index.htm
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Men Lupus in Men Source: Lupus Foundation of America http://www.lupus.org/education/brochures/lupusmen.html
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Organizations Alliance for Lupus Research http://www.lupusresearch.org/ American Autoimmune Related Diseases Association http://www.aarda.org/ Lupus Foundation of America http://www.lupus.org/ National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/
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Research Delivering on the Promise in Systemic Lupus Erythematosus Source: Arthritis Foundation http://www.arthritis.org/research/research_program/Lupus/default.asp Lupus Brain Damage Pathway Illuminated Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.nih.gov/news/pr/nov2001/niams-19.htm
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Statistics Late Onset Lupus Source: Lupus Foundation of America http://www.lupus.org/education/lateonset.html Lupus Source: National Center for Chronic Disease Prevention and Health Promotion http://www.cdc.gov/od/oc/media/pressrel/fs020503.htm
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Teenagers Life with Lupus Source: Nemours Foundation http://kidshealth.org/teen/diseases_conditions/bones/lupus.html
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Women Pregnancy and Lupus Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/hi/topics/lupus/lupusguide/chppis11.htm
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on lupus. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
What is Systemic Lupus Erythematosus? Source: Baltimore, MD: Maryland Lupus Foundation. 199x. 4 p. Contact: Available from Maryland Lupus Foundation, Inc. 7400 York Road, Baltimore, MD 21204. (410) 337-9000; (800) 777-0934 in Maryland only. PRICE: Single copy free. Summary: Systemic lupus erythematosus (SLE) is a chronic, inflammatory disease in which the body's immune system forms antibodies that attack healthy tissues and organs. This brochure presents an introduction to SLE, including the three different types of lupus, the symptoms of the disease, causes, diagnostic tests used to confirm lupus, and how the disease is treated. Symptoms of lupus include joint involvement and ulcers inside the mouth.
•
Lupus Source: Atlanta, GA: Arthritis Foundation. 1996. 28 p. Contact: Arthritis Foundation, P.O. Box 7669, Atlanta, GA 30357-0669. (800) 283-7800. (800) 207-8633. Summary: This booklet for individuals with systemic lupus erythematosus (SLE) provides an overview of this disease. It describes SLE, discoid lupus, drug-induced lupus, and crossover syndromes. The booklet discusses the role of immune system malfunctioning in lupus and examines the role of hereditary in acquiring the disease. It outlines the primary and other symptoms of lupus; explains how lupus is diagnosed; and discusses the options available for treating lupus, including medications, exercise, and diet. In addition, the booklet addresses special concerns dealing with sun and artificial light exposure, pregnancy and contraception, kidney dialysis and transplantation, infections, and vaginal dryness; offers tips for coping with lupus; and identifies sources of additional information.
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•
Handout on Health: Systemic Lupus Erythematosus Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1997. 35 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail:
[email protected]. Website: www.niams.nih.gov. PRICE: Single copy free. Order Number: AR-96HH (booklet), or AR-96L HH (large print). Summary: This booklet is for people with systemic lupus erythematosus (SLE), family members, friends, and others and focuses on the causes, symptoms, diagnosis, and treatment of SLE. It explains who is more likely to get SLE, what parts of the body it can affect, the characteristic cycles of illness and remission, and the several kinds of lupus. Also discussed are the factors that may influence getting this disease, common symptoms, how a doctor makes a diagnosis, the goals of treatment, and the various medications used to treat lupus. The booklet presents some alternative therapies that may help patients cope with the stress of living with a chronic illness, emphasizing the importance of understanding the disease and its impact, receiving regular health care, developing strategies for maintaining wellness, and establishing a good support system. Also included are issues on the impact of lupus for women considering pregnancy. The booklet also describes current research on the causes and treatments for lupus by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and other components of the National Institutes of Health. It then refers the reader to the network of voluntary health organizations for additional information about lupus. A large print version of this booklet is also available.
•
Lupus Erythematosus: A Patient's Guide Source: Rockville, MD: Lupus Foundation of America. 2000. 40 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 toll-free or (301) 670-9292. Website: www.lupus.org/lupus. PRICE: 3.95 plus shipping and handling. Summary: This booklet provides people who have lupus erythematosus (LE) with information on the types, frequency, cause, diagnosis, symptoms, and treatment of this autoimmune disease. LE involves changes in the immune system so that it attacks the body's own tissues. LE usually appears in one of two forms: cutaneous lupus erythematosus (CLE) or systemic lupus erythematosus (SLE). Other variants include drug induced lupus, neonatal lupus, mixed connective tissue disease, and undifferentiated connective tissue disease. Most patients with CLE and SLE are women. The severity of lupus varies from mild to life threatening. The cause of CLE and SLE is unknown, but genetic and environmental factors are believed to be involved. Although CLE can be diagnosed by the history and appearance of the skin rash, diagnosing SLE is more difficult. A complete medical history, a physical examination, and laboratory tests are important components of the diagnostic workup. A diagnosis of SLE can be made if 4 of 11 diagnostic criteria are met. Special tests for SLE may be performed to confirm the diagnosis. Symptoms are varied, and any part of the body may be involved. The booklet presents the cutaneous, musculoskeletal, cardiovascular, gastrointestinal, urogenital, lymphatic, and neurological symptoms of SLE. Other considerations addressed include flares, employment, pregnancy, contraception, and hormone replacement therapy. The booklet also discusses drugs available to treat SLE, including aspirin and nonsteroidal antiinflammatory drugs, antimalarial drugs, corticosteroids, and immunosuppressives.
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Another topic is self care, focusing on physical measures and preventive coping strategies. The booklet includes a glossary of terms and information on the Lupus Foundation of America. 1 table. •
The Many Shades of Lupus: Information for Multicultural Communities Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 2001. 36 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 toll-free or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail:
[email protected]. Website: www.niams.nih.gov. PRICE: One to 10 copies available free. Order Number: AR-231 (booklet). Summary: This booklet uses a question and answer format to provide people who have lupus with information on this autoimmune disease. Lupus can affect many parts of the body and can affect different people in different ways. The cause of lupus is unknown, but genetic and environmental factors are believed to be involved. The main types are systemic lupus erythematosus, discoid lupus erythematosus, and drug induced lupus. The booklet outlines the signs and symptoms of lupus, explains what a flare is, identifies the population most commonly affected by lupus, and discusses its diagnosis and management. In addition, the booklet highlights research on lupus and presents government and nongovernment organizations that can provide additional information about lupus.
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Kidney Disease and Lupus. [La Enfermedad Renal y Lupus] Source: Rockville, MD: Lupus Foundation of America, Inc. 1996. 2 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Picard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. PRICE: Single copy free; bulk copies available. Summary: This brochure provides information about lupus nephritis or lupus glomerulonephritis, the kidney disease that occurs in systemic lupus erythematosus. Topics include the clinical course of lupus nephritis; studies used to evaluate lupus nephritis, including urinalysis, blood studies, 24-hour urine collection, x-ray studies, and kidney biopsy; treatment options, including the use of corticosteroids and immunosuppressive drugs; and progressive loss of kidney function and renal failure attributable to lupus nephritis. The brochure concludes with a description of the goals and activities of the Lupus Foundation of America. The brochure is available in English or Spanish.
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Lupus Guide Patient Information Handouts Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1998. 28 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail:
[email protected]. Website: www.niams.nih.gov. PRICE: Single copy free. Order Number: AR-205.
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Summary: This compilation of 16 reproducible fact sheets provides information useful for people who have lupus and for the patient care team. Fact sheet topics include living with lupus, preventing fatigue due to lupus, exercising with lupus, preventing a lupus flare, recognizing serious conditions associated with lupus, dealing with joint pain, recognizing and caring for skin conditions, handling a fever, eating nutritious meals, and coping with sexual issues and pregnancy. In addition, the fact sheets provide information on various medications, including nonsteroidal anti-inflammatory drugs, antimalarials, corticosteroids, azathioprine, and cyclophosphamide. The medication fact sheets highlight possible side effects and precautions and provide space to record personal instructions for taking the medication. •
Systemic Lupus Erythematosus Source: American College of Rheumatology. 2000. 2 p. Contact: Available from American College of Rheumatology. Website: www.rheumatology.org. Summary: This fact sheet discusses systemic lupus erythematosus (SLE), a chronic autoimmune disorder. Symptoms are varied but may include skin rashes, mouth and nose sores, arthritis, nervous system disorders, and kidney inflammation. Diagnosis is based on lab studies , particularly the antinuclear antibody test. Although SLE is chronic, it goes through active and inactive phases. Treatment includes NSAIDs and corticosteroids for inflammation, antimalarials such as hydroxychloroquine for reducing SLE activity, and immunosuppressive drugs such as azathioprine and cyclophosphamide for more severe SLE.
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Lupus Fact Sheet Source: Rockville, MD: Lupus Foundation of America, Inc. 199x. 2 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Web Site: www.lupus.org/lupus. PRICE: Sold as part of a set; call for price. Summary: This fact sheet for people with lupus provides an overview of this chronic, autoimmune disease which causes inflammation of various parts of the body, particularly the skin, joints, blood, and kidneys. The fact sheet presents information about the prevalence, cause, and symptoms of the disease. In addition, it provides a selftest for lupus, and it includes the address and telephone number for the Lupus Foundation of America.
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Lupus and Kidney Disease Source: New York, NY: National Kidney Foundation. 1992. 3 p. Contact: Available from National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010. PRICE: Single copy free. Summary: This fact sheet provides basic information about lupus erythematosus and kidney disease. Written in a question and answer format, the fact sheet defines lupus and then covers its causes; symptoms; how lupus can harm the kidneys; diagnosis and treatment; side effects of immunosuppressive drugs used to treat lupus; dietary considerations; diagnosing any kidney problems related to lupus; what happens if the kidneys fail; the long-term prognosis for patients with lupus; and patient self-care and
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management considerations. The fact sheet concludes with a brief description of the National Kidney Foundation (NKF) and its activities. •
Discoid Lupus Erythematosus Source: Kirksville, MO: American Osteopathic College of Dermatology (AOCD). 2001. 2 p. Contact: Available online from American Osteopathic College of Dermatology. 1501 East Illinois Street, P.O. Box 7525, Kirksville, MO 63501. (800) 449-2623 or (660) 665-2184. Fax (660) 627-2623. E-mail:
[email protected]. Website: www.aocd.org/skin/dermatologic_diseases/ index.html. Summary: This fact sheet provides people who have discoid lupus erythematosus (DLE) with information on this chronic skin condition consisting of sores with inflammation and scarring. DLE, which is more prevalent in women than in men, occurs most often on the face, ears, and scalp. A small percentage of people with DLE can develop systemic disease. Although the exact cause is unknown, DLE is thought to be an autoimmune disease in which the body's immune system attacks the skin. Treatment involves application of cortisone ointment to the skin in the involved areas. Cortisone can also be injected into the lesions. This is usually more effective than the ointment form. A drug known as Plaquenil will improve the condition, but people who take this drug need eye examinations once a year to prevent damage to the retina, as well as periodic blood work. Followup is needed every 6 months to once a year to make sure that the disease is not spreading to the internal organs and to minimize scarring. 2 figures.
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Lupus Guide Patient Information Handouts: Pregnancy and Lupus Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1998. 3 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail:
[email protected]. Website: www.niams.nih.gov. PRICE: Available only as part of a package of patient information sheets; single copy of package free. Order Number: AR-205. Summary: This fact sheet provides women who have systemic lupus erythematosus and the patient care team with information about pregnancy and lupus. Although most women with lupus can safely become pregnant, the disease should be under control or in remission before conception takes place. The pregnancy should be monitored by an obstetrician experienced at managing high-risk pregnancies, and delivery should be planned at a hospital that can manage a high-risk patient and provide specialized care for the woman and her baby. Problems that can affect a pregnant woman who has lupus include the development of a lupus flare and pregnancy-induced hypertension. In most cases, babies born to women with lupus have no greater chance of birth defects or mental retardation than babies born to women without lupus. However, about 3 percent of babies born to mothers with lupus will have neonatal lupus. This condition usually disappears by the time the infant is 3 to 6 months old and does not recur. The fact sheet offers tips for planning for a pregnancy and coping with the physical and emotional changes that occur during the postpartum period. Reasons why breastfeeding may not be possible are presented. In addition, the fact sheet offers self-care tips and provides space for making additional notes.
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Patient Notes: Lupus Source: Postgraduate Medicine. 103(3): 277-278. March 1998. Summary: This handout uses a question and answer format to provide people who have lupus with information on the cause, types, symptoms, and diagnosis of this autoimmune disorder, as well as its treatment. The cause is unclear, but some factors that may contribute to lupus include infection, exposure to ultraviolet light, use of certain drugs, and very severe stress. Lupus is more common in women and in various ethnic groups. Types include drug-related lupus, discoid lupus, and systemic lupus erythematosus. Although the symptoms may imitate those of other diseases, some common symptoms are swelling, stiffness, and pain in the same joints on both sides of the body. Other symptoms are mild fever, fatigue, weakness, muscle soreness, photosensitivity, red and raised patches on the skin, hair loss, mouth or nose sores, and white or purple fingers or toes after exposure to stress or cold. There is no single diagnostic test for lupus. Although there is no treatment, lupus symptoms may be alleviated by using nonsteroidal anti-inflammatory drugs, mild analgesics, corticosteroids, antimalarials, and immunosuppressive agents. In addition, the handout offers tips on caring for oneself. 2 figures.
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Managing Lupus Source: San Bruno, CA: StayWell Company. 1997. 6 p. Contact: Available from StayWell Company. 1100 Grundy Lane, San Bruno, CA 940663030. (800) 333-3032. Website: www.staywell.com. PRICE: Call or write for current pricing on single and bulk orders. Summary: This illustrated brochure provides people who have lupus with information on living well with a chronic disease. Systemic lupus causes the body's immune system to attack its own cells and tissues. Various joints and organs can be affected. Diagnosis is based on information obtained through a medical history, a physical examination, and imaging tests. The brochure outlines the symptoms of lupus, offers tips to help maintain health, and provides suggestions on taking medications. In addition, the brochure identifies sources of information.
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What is Lupus? Source: Rockville, MD: Lupus Foundation of America, Inc. 1998. 12 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Website: www.lupus.org/lupus. PRICE: Available as part of a package of 21 different lupusrelated brochures for $3.95 plus shipping and handling. Summary: This pamphlet for people with lupus provides an overview of this chronic inflammatory disease that can affect various parts of the body. It describes the discoid, systemic, and drug-induced forms of lupus and discusses the cause of lupus. Although the cause is unknown, scientists believe that there is a genetic predisposition to the disease and that certain environmental factors may trigger the disease. The pamphlet outlines the symptoms of lupus and discusses its diagnosis. Lupus is diagnosed through information obtained from the medical history, a physical examination, and diagnostic testing. There are 11 symptoms that help physicians distinguish lupus from other diseases, and various laboratory tests may help diagnosis this disease. Tests include the lupus erythematosus cell test, the immunofluorescent antinuclear antibody test, and tests that measure complement levels in the blood and individual antigen antibody
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reactions. Skin and kidney biopsies may also be performed. The pamphlet describes the commonly prescribed medications for lupus, including nonsteroidal anti-inflammatory drugs, acetaminophen, corticosteroids, antimalarials, immunomodulating drugs, and anticoagulants. Other topics discussed include nutrition and diet, pregnancy, and the prognosis for people with lupus. The pamphlet also provides information on the Lupus Foundation of America. 2 tables. •
Childhood Lupus Source: Rockville, MD: Lupus Foundation of America, Inc. 2000. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 toll-free or (301) 670-9292. Website: www.lupus.org/lupus. PRICE: $0.25 each plus shipping and handling; brochures must be ordered in quantities of 100. Summary: This pamphlet provides parents who have a child with lupus with information on some of the medical considerations involved. The first step for every family is to be sure the diagnosis is correct. Next, the family should comply with physician instructions, because compliance has been shown to be one of the most important factors in determining outcome for people with systemic lupus erythematosus. The most important issue for parents of children with lupus is dealing with the side effects of drugs such as corticosteroids. Cytotoxic immunosuppressive drugs are an alternative to high doses of corticosteroids; however, they may increase a child's risk of developing certain forms of cancer. The pamphlet also addresses the social and psychological concerns that can have an impact on the outcome for children who have lupus and their families. These issues include dealing with activities where a child may be away overnight, educating a child about his or her condition and its treatment, educating others about a child's lupus, and coping with a child's anger or depression. The pamphlet also includes a brief discussion on the genetic component of lupus. The pamphlet concludes with information on the Lupus Foundation of America.
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Lupus in Overlap With Other Connective Tissue Diseases Source: Rockville, MD: Lupus Foundation of America, Inc. 2000. 6 p. Contact: Available from Lupus Foundation of America, Inc. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 toll-free or (301) 670-9292. Website: www.lupus.org/lupus. PRICE: $0.25 each plus shipping and handling; brochures must be ordered in quantities of 100. Summary: This pamphlet provides people who have lupus with information on other connective tissue diseases that might overlap with it. The pamphlet lists the common features of these diseases. This is followed by a description of various connective tissue diseases that may coexist with lupus, including rheumatoid arthritis, myositis, scleroderma, mixed connective tissue disease, and Sjogren's syndrome. In addition, the pamphlet presents data on the frequency of overlap syndromes in people with lupus. Other topics include the role of heredity in overlap and the prognosis for people with lupus and overlap syndromes. The pamphlet concludes with information on the Lupus Foundation of America. 1 table.
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Drug-Induced Lupus Erythematosus Source: Rockville, MD: Lupus Foundation of America. 1999. 6 p.
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Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus. PRICE: Available as part of a package of 21 different lupus related brochures for $3.95 plus shipping and handling. Summary: This pamphlet uses a question and answer format to provide people who have lupus with information on drug-induced lupus erythematosus (DILE). This form of lupus is a side-effect of long-term use of certain medications used to treat chronic diseases (especially procainamide, hydralazine, and quinidine). The only well-defined genetic risk factor in DILE is the slow drug acetylation phenotype. Circumstantial evidence suggests that the metabolic change a drug undergoes in the body, rather than the drug itself, makes the drug able to react with the immune system. People with DILE may experience flu-like symptoms. The features are the same regardless of the medication. Tests that can help with diagnosis include the antinuclear antibody test and the antihistone test. The most important aspect of treating DILE is to identify the medication that is likely to be causing the problem and then discontinue it. Although most people recover once they stop using the medication, they may develop the syndrome if they take the medication again. The pamphlet explains the difference between DILE and systemic lupus erythematosus, lists drugs reported to induce lupuslike disease, and provides information on the Lupus Foundation of America. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “lupus” (or synonyms). The following was recently posted: •
Systemic lupus erythematosus (SLE) Source: Finnish Medical Society Duodecim - Professional Association; 2001 April 30; Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=3390&nbr=2616&a mp;string=lupus Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Handout on Health: Systemic Lupus Erythematosus (SLE) Summary: This consumer health education booklet describes this disease and its symptoms and contains information about diagnosis and treatment as well as current research efforts supported by the National Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2929
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Lupus Nephritis Summary: Brief overview of the symptoms, diagnosis, and treatment of lupus nephritis. Source: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6519
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Lupus: A Patient Guide for Nurses and Other Health Professionals Summary: Lupus: A Patient Care Guide for Nurses and Other Health Professionals Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6763
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Lupus: Causes, Symptoms, Testing, Treatment Summary: Provides a general overview of lupus, including the definition, types, causes, symptoms, diagnosis, triggers, treatment, and prognosis. Source: Lupus Foundation of America http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6439
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The Many Shades of Lupus: Information for Multicultural Communities Summary: This consumer health education booklet describes this disease and its symptoms as it relates to multicultural communities. Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2930
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The Neurological Sequelae Of Lupus Summary: A general overview of neurological sequelae of lupus that includes a description of the disorder, treatment, prognosis and research information. Source: National Institute of Neurological Disorders and Stroke, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3798
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What is Lupus? Source: Lupus Foundation of Greater Washington http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6053 The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an
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ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to lupus. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is http://www.rarediseases.org/. A complete guide on lupus can be purchased from NORD for a nominal fee. Additional Web Sources
A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Associations and Lupus The following is a list of associations that provide information on and resources relating to lupus: •
American Autoimmune Related Diseases Association, Inc. Telephone: (586) 776-3900 Fax: (586) 776-3903 Email:
[email protected] Web Site: http://www.aarda.org/ Background: The American Autoimmune Related Diseases Association, Inc. (AARDA) is a national not-for-profit voluntary health agency dedicated to bringing a national focus to autoimmunity, a major cause of serious chronic diseases. The Association was founded for the purposes of supporting research to find a cure for autoimmune diseases and providing services to affected individuals. In addition, the Association s goals
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include increasing the public s awareness that autoimmunity is the cause of more than 80 serious chronic diseases; bringing national focus and collaborative effort among state and national voluntary health groups that represent autoimmune diseases; and serving as a national advocate for individuals and families affected by the physical, emotional, and financial effects of autoimmune disease. The American Autoimmune Related Diseases Association produces educational and support materials including fact sheets, brochures, pamphlets, and a newsletter entitled 'In Focus.'. Relevant area(s) of interest: Lupus •
American Juvenile Arthritis Organization Telephone: (404) 872-7100 Toll-free: (800) 283-7800 Fax: (404) 872-9559 Email:
[email protected] Web Site: http://www.arthritis.org Background: The American Juvenile Arthritis Organization (AJAO), a not-for-profit organization, is a Council of the Arthritis Foundation devoted to serving the needs of children, teens, and young adults with childhood rheumatic diseases and their families. These diseases include juvenile rheumatoid arthritis, lupus (systemic lupus erythematosis), ankylosing spondylitis and other related conditions. Juvenile arthritis is medically different from the adult form of arthritis and may be far more severe in some cases. The American Juvenile Arthritis Organization was founded in 1981 to help serve the special needs of affected individuals and families, friends, and health care professionals. The Organization enables members to exchange ideas and support and serves as a clearinghouse of information for the public on topics from medications to educational rights to social services. It sponsors an annual conference; monitors and promotes legislation that benefits individuals with Juvenile Arthritis; provides appropriate referrals; and sponsors research concerning potential causes, improved treatments, preventive measures, and possible cures. The American Juvenile Arthritis Organization provides a variety of educational materials including a quarterly newsletter and educational brochures. Relevant area(s) of interest: Lupus
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British Sjogren's Syndrome Association Telephone: (121) 455-6532 Fax: (121) 455-6532 Email:
[email protected] Web Site: http://ourworld.compuserve.com/homepages.BSSAssociation Background: The British Sjogren's Syndrome Association (BSSA) is a registered charity dedicated to providing mutual support and information to individuals affected by Sjogren syndrome. Sjogren syndrome is an autoimmune disorder characterized by degeneration of the mucus-secreting glands, particularly the tear ducts of the eyes (lacrimal) and saliva glands of the mouth. Autoimmune disorders are caused when the body's natural defenses (antibodies, lymphocytes, etc.) against invading organisms suddenly begin to attack healthy tissue. Sjogren syndrome is also associated with inflammatory disorders such as arthritis or lupus. Founded in 1986, the BSSA strives to fulfill its mission to disseminate current information on the treatment of Sjogren syndrome to affected individuals and medical professionals. In addition to holding
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regular meetings in several locations throughout England, BSSA publishes journals, informational brochures, and a quarterly newsletter. •
European Lupus Erythematosus Federation Telephone: 44-1708-73 12 51 Fax: 44-1708-73 12 52 Email:
[email protected] Web Site: http://www.elef.rheumanet.org/ Background: The European Lupus Erythematosus Federation (ELEF) is an international voluntary federation that consists of national lupus groups throughout Europe. Systemic lupus erythematosus (SLE), also known as lupus, is an autoimmune disorder characterized by chronic inflammation affecting connective tissues of the body. Different tissues and organs may be affected, and the range and severity of associated symptoms and findings may vary from case to case. In some affected individuals, symptoms may include extreme fatigue; muscle pain; joint swelling, stiffness, and pain; skin rashes; hair loss; and other abnormalities. Established in 1989, the European Lupus Erythematosus Federation currently represents 15 countries, 16 lupus organizations, and approximately 16,500 affected individuals and family members. The ELEF is committed to collecting information on all medical and psychosocial aspects of lupus; promoting awareness of the disease among individuals with lupus, the general public, and members of the health, welfare, and medical professions; and encouraging and conducting surveys and research projects related to the disease and publishing the results of such research. The Federation is also dedicated to promoting awareness of lupus support groups that are available for affected individuals and family members in each member country; sponsoring or promoting European symposia on all aspects of lupus; gaining representation on any European or international body whose interests will be of benefit to members of the Federation; and assisting with the establishment of support groups in other European countries where none currently exists. The Federation also conducts international surveys on lupus, publishes a biannual newsletter entitled 'Caring and Sharing,' and has a web site on the Internet.
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Lupus Canada Telephone: (403) 274-5599 Toll-free: (800) 661-1468 Fax: (403) 274-5599 Email:
[email protected] Web Site: http://www.lupuscanada.org Background: Lupus Canada is a national association of regional lupus support groups and their various branches. These groups of volunteers are dedicated to providing support and information to people who have lupus, their families, and friends. Lupus is a chronic autoimmune disorder that can affect any organ of the body. In lupus, the body's immune system that defends against invading or 'foreign' organisms (e.g., viruses, bacteria, germs) begins to malfunction and fails to distinguish between the body s own tissues and these foreign invaders. As a result, the body's natural defenses (antibodies) begin to attack the body's own tissue. Established in 1987, Lupus Canada produces educational materials including a pamphlet entitled 'Lupus: An Introduction,' and a booklet entitled 'Lupus: The Disease With 1000 Faces.'. Relevant area(s) of interest: Lupus
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Lupus Foundation of America, Inc Telephone: (301) 670-9292 Toll-free: (800) 558-0121 Fax: (301) 670-9486 Web Site: http://www.lupus.org Background: The Lupus Foundation of America is a national not-for-profit organization that was established in 1977. The primary purposes of the Foundation are the eradication of Lupus through research, the early detection of undiagnosed cases through awareness promotion, and the alleviation of suffering through patient support programs. The Lupus Foundation has more than 90 local chapters serving hundreds of thousands of people throughout the United States and 73 International Associated Groups in 37 countries worldwide. The Services provided by the Foundation and its chapters include informational materials, referrals, patient educational meetings and seminars, support groups, hospital visits, grants, and bequests. The Foundation functions as an advocate for people with Lupus and seeks to raise awareness and understanding of the disorder among elected and appointed government officials. To this end, the Foundation participates in coalitions with other health agencies to make its mission known to decision and policy makers. A wide variety of educational materials are produced by the organization including brochures, pamphlets, and a newsletter entitled 'Lupus News.' Some materials are available in Spanish. Relevant area(s) of interest: Lupus
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Lupus UK Telephone: 01708 731251 Fax: 01708 731252 Email:
[email protected] Web Site: http://www.geocities.com/HotSprings/2911/ Background: Lupus UK is a voluntary organization in the United Kingdom dedicated to providing information and support to individuals affected by systemic lupus erythematosus (SLE), an autoimmune disorder that is characterized by chronic inflammation affecting the skin, joints, or other connective tissues of the body. Different tissues and organs may be involved, and the range and severity of associated symptoms and findings may vary greatly from case to case. In some individuals with the disorder, symptoms may include weakness and fatigue; persistent flu-like symptoms; joint inflammation, swelling, stiffness, and pain; skin rashes, such as the appearance of a rash across the bridge of the nose and the cheeks ('butterfly' rash); abnormal sensitivity of the skin to light; hair loss; and other abnormalities. Lupus UK was established in 1978 and currently consists of 27 regional groups throughout Great Britain and Northern Ireland. The organization, which is a self-help group run by volunteers, is committed to providing support and assistance to all affected individuals; promoting communication between members and the medical professionals involved in their care; and offering practical assistance. Lupus UK is also dedicated to promoting professional and public awareness of lupus by gathering and publishing information on all aspects of the disease; raising funds to assist affected individuals and to finance research projects; and working with other organizations to promote the aims of Lupus UK. Affected individuals and family members who join the organization are automatically enrolled in a Lupus UK regional support group; have the opportunity to participate in educational and social meetings; and receive a local newsletter as well as a national newsletter
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entitled 'News and Views.' Lupus UK also offers a factsheet series and several books on the disorder and has a web site on the Internet. •
Sjogren's Syndrome Association, Inc. / Association du Syndrome deSjogren Inc Telephone: (514) 934-3666 Fax: (514) 934-1241 Email: None. Web Site: None Background: Sjogren's Syndrome Association, Inc. (Association du Syndrome de Sjogren, Inc.) is a voluntary not-for-profit health organization in Montreal, Canada dedicated to providing support and education to individuals affected by Sjogren's syndrome, an immunologic disorder characterized by deficient moisture production of the tear duct (lacrimal), salivary, and/or other glands. Associated symptoms typically include abnormal dryness of the eyes (keratoconjunctivitis sicca), the mouth (xerostomia), and other affected glands. The disorder most commonly affects females over the age of 40 and often occurs in association with certain autoimmune, connective tissue disorders (e.g., rheumatoid arthritis, systemic lupus erythematosus, or scleroderma). The Sjogren's Syndrome Association was formed in 1994 to provide affected individuals and family members with practical information and coping strategies for living with Sjogren's syndrome. The organization currently has approximately 160 members and a chapter in Ontario, Canada. The Association also gathers and disseminates medical information relating to Sjogren's syndrome, promotes research, and represents the interests all individuals with the disease. In addition, the Sjogren's Syndrome Association conducts regular group meetings and physician conferences, promotes public awareness of the disorder, and offers a variety of educational materials including brochures and a regular newsletter that contains medical news, information on current research, and helpful tips for daily living.
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to lupus. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with lupus. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about lupus. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations.
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The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “lupus” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “lupus”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “lupus” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “lupus” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.27
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
27
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)28: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
28
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 419
•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 421
•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
422 Lupus
•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
423
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on lupus: •
Basic Guidelines for Lupus Lupus - resources Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002160.htm Lupus anticoagulant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000547.htm Lupus nephritis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000481.htm
•
Signs & Symptoms for Lupus Bleeding gums Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003062.htm Blood in the urine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003138.htm
424 Lupus
Bruising Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003235.htm Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Decreased urine output Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003147.htm Edema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Joint pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Joint swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003262.htm Menstrual periods, abnormal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003263.htm Nosebleed - symptom Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003106.htm Rash Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Skin rash Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Skin redness or inflammation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Vaginal bleeding between periods Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003156.htm
Online Glossaries 425
•
Diagnostics and Tests for Lupus ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm Antinuclear antibody Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm BUN Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003474.htm Casts Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003586.htm Complement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003456.htm Complement component 3 Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003539.htm Creatinine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm Dialysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003421.htm Kidney biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003907.htm PTT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003653.htm Urinalysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003579.htm Urine immunoglobulin light chain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003597.htm
•
Nutrition for Lupus Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm
•
Surgery and Procedures for Lupus Abortion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002912.htm
426 Lupus
Kidney transplant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003005.htm •
Background Topics for Lupus Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Antibodies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002223.htm Auscultation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002226.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Blood clots Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm Clot Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Inflammatory response Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm Nose bleeds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000020.htm Renal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002289.htm Titer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002328.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
Online Glossaries 427
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
429
LUPUS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Actin: Essential component of the cell skeleton. [NIH]
430 Lupus
Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [NIH] Activated Protein C Resistance: A hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). The activated form of Factor V (Factor Va) is more slowly degraded by activated protein C. Factor V Leiden mutation (R506Q) is the most common cause of APC resistance. [NIH] Acute Disease: Disease having a short and relatively severe course. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive
Dictionary 431
immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Albuminuria: More than normal amounts of a protein called albumin in the urine.
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Albuminuria may be a sign of kidney disease. [NIH] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkalinization: The process by which a substance becomes an alkali. An alkali is the opposite of an acid. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits trypsin, neutrophil elastase, and other proteolytic enzymes. Commonly referred to as alpha 1-proteinase inhibitor (A1PI), it exists in over 30 different biochemical variant forms known collectively as the PI (protease inhibitor) system. Hereditary A1PI deficiency is associated with pulmonary emphysema. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]
Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and
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tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]
Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
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Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasma: A genus of gram-negative bacteria whose organisms are obligate parasites of vertebrates. Species are transmitted by arthropod vectors with the host range limited to ruminants. Anaplasma marginale is the most pathogenic species and is the causative agent of severe bovine anaplasmosis. [NIH] Anaplasmosis: A disease of cattle caused by parasitization of the red blood cells by bacteria of the genus Anaplasma. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgen-Binding Protein: Carrier proteins produced in the Sertoli cells of the testis, secreted into the seminiferous tubules, and transported via the efferent ducts to the epididymis. They participate in the transport of androgens. Androgen-binding protein has the same amino acid sequence as sex hormone binding-globulin. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angiitis: Inflammation of a vessel, chiefly of a blood or a lymph vessel; called also vasculitis. [EU] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH]
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Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]
Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibodies, Anticardiolipin: Antiphospholipid antibodies found in association with systemic lupus erythematosus (lupus erythematosus, systemic), antiphospholipid syndrome, and in a variety of other diseases as well as in healthy individuals. The antibodies are detected by solid-phase immunoassay employing the purified phospholipid antigen cardiolipin. [NIH] Antibodies, Antiphospholipid: Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus, antiphospholipid syndrome, related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH]
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Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiphospholipid Syndrome: The presence of antibodies directed against phospholipids (antibodies, antiphospholipid). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (antibodies, anticardiolipin). Present also are high levels of lupus anticoagulant (lupus coagulation inhibitor). [NIH] Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH]
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Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Apheresis: Components plateletpheresis. [NIH]
being
separated
out,
as
leukapheresis,
plasmapheresis,
Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the
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most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthralgia: Pain in the joint. [NIH] Arthritis, Rheumatoid: A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated. [NIH] Arthropathy: Any joint disease. [EU] Arthropod Vectors: Arthropods, other than insects and arachnids, which transmit infective organisms from one host to another or from an inanimate reservoir to an animate host. [NIH] Articular: Of or pertaining to a joint. [EU] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a
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variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Audiovisual Aids: Auditory and visual instructional materials. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as
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sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some
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cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biopterin: A natural product that has been considered as a growth factor for some insects. [NIH]
Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blister: Visible accumulations of fluid within or beneath the epidermis. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood Proteins: Proteins that are present in blood serum, including serum albumin, blood coagulation factors, and many other types of proteins. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Viscosity: The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
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Body Burden: The total amount of a chemical, metal or radioactive substance present at any time after absorption in the body of man or animal. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Image: Individuals' personal concept of their bodies as objects in and bound by space, independently and apart from all other objects. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone metastases: Cancer that has spread from the original (primary) tumor to the bone. [NIH]
Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bullous: Pertaining to or characterized by bullae. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcifediol: The major circulating metabolite of vitamin D3 produced in the liver and the best indicator of the body's vitamin D stores. It is effective in the treatment of rickets and osteomalacia, both in azotemic and non-azotemic patients. Calcifediol also has mineralizing
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properties. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcinosis: Pathologic deposition of calcium salts in tissues. [NIH] Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning. [NIH] Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency, or other output. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the
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interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiolipins: Acidic phospholipids composed of two molecules of phosphatidic acid covalently linked to a molecule of glycerol. They occur primarily in mitochondrial inner membranes and in bacterial plasma membranes. They are the main antigenic components of the Wassermann-type antigen that is used in nontreponemal syphilis serodiagnosis. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual
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patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue,
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particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Child Rearing: The training or bringing-up of children by parents or parent-substitutes. It is used also for child rearing practices in different societies, at different economic levels, in different ethnic groups, etc. It differs from parenting in that in child rearing the emphasis is on the act of training or bringing up the child and the interaction between the parent and child, while parenting emphasizes the responsibility and qualities of exemplary behavior of
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the parent. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorambucil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Chlordecone: A highly chlorinated polycyclic hydrocarbon insecticide whose large number of chlorine atoms makes it resistant to degradation. It has been shown to be toxic to mammals and causes abnormal cellular changes in laboratory animals. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecalciferol: An antirachitic oil-soluble vitamin. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic granulocytic leukemia: A slowly progressing disease in which too many white
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blood cells are made in the bone marrow. Also called chronic myelogenous leukemia or chronic myeloid leukemia. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cicatrix: The formation of new tissue in the process of wound healing. [NIH] Cicatrix, Hypertrophic: An elevated scar, resembling a keloid, but which does not spread into surrounding tissues. It is formed by enlargement and overgrowth of cicatricial tissue and regresses spontaneously. [NIH] Cidofovir: A drug used to treat infection caused by viruses. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cladribine: An antineoplastic agent used in the treatment of lymphoproliferative diseases including hairy-cell leukemia. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clodronate: A drug used as treatment for hypercalcemia (abnormally high levels of calcium in the blood) and for cancer that has spread to the bone (bone metastases). It may decrease pain, the risk of fractures, and the development of new bone metastases. [NIH] Clonal Deletion: Removal, via cell death, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion. [NIH]
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Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Duct: Spiral tube in the bony canal of the cochlea, lying on its outer wall between the scala vestibuli and scala tympani. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognitive restructuring: A method of identifying and replacing fear-promoting, irrational beliefs with more realistic and functional ones. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH]
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Common Variable Immunodeficiency: Heterogeneous group of immunodeficiency syndromes characterized by hypogammaglobulinemia of most isotypes, variable B-cell defects, and the presence of recurrent bacterial infections. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementarity Determining Regions: Three regions (CDR1, CDR2 and CDR3) of amino acid sequence in theimmunoglobulin variable region that are highly divergent. Together the CDRs from the light and heavy immunoglobulin chains form a surface that is complementary to the antigen. These regions are also present in other members of the immunoglobulin superfamily, for example, T-cell receptors (receptors, antigen, T-cell). [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Complete response: The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. [NIH]
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Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is
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represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Corn Oil: Oil from corn or corn plant. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried
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by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Coumarins: Synthetic or naturally occurring substances related to coumarin, the deltalactone of coumarinic acid. Coumarin itself occurs in the tonka bean. The various coumarins have a wide range of proposed actions and uses including as anticoagulants, pharmaceutical aids, indicators and reagents, photoreactive substances, and antineoplastic agents. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH]
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Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Cytidine: A pyrimidine nucleoside that is composed of the base cytosine linked to the fivecarbon sugar D-ribose. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytopenia: A reduction in the number of blood cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [NIH]
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Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule
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cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depigmentation: Removal or loss of pigment, especially melanin. [EU] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatitis: Any inflammation of the skin. [NIH] Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH]
Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusivity: Of a reverberant sound field. The degree to which the directions of propagation of waves are random from point to point. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH]
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Dilatation: The act of dilating. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discoid: Shaped like a disk. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Docosahexaenoic Acids: C22-unsaturated fatty acids found predominantly in fish oils. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU]
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Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dry Eye Syndrome: A common condition that occurs when the eyes do not produce enough tears to keep the eye moist and comfortable. Common symptoms of dry eye include pain, stinging, burning, scratchiness, and intermittent blurring of vision. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]
Ectopic: Pertaining to or characterized by ectopia. [EU] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH]
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Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efferent Pathways: Nerve structures through which impulses are conducted from a nerve center toward a peripheral site. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Ellagic Acid: A fused four ring compound occurring free or combined in galls. Isolated from the kino of Eucalyptus maculata Hook and E. Hemipholia F. Muell. Activates Factor XII of the blood clotting system which also causes kinin release; used in research and as a dye. [NIH]
Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation
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phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Empyema: Presence of pus in a hollow organ or body cavity. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic
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endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]
Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been
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developed. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelioid Cells: Characteristic cells of granulomatous hypersensitivity. They appear as large, flattened cells with increased endoplasmic reticulum. They are believed to be activated macrophages that have differentiated as a result of prolonged antigenic stimulation. Further differentiation or fusion of epithelioid cells is thought to produce multinucleated giant cells. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Epoprostenol: A prostaglandin that is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. It is a potent inhibitor of platelet aggregation. The sodium salt has been also used to treat primary pulmonary hypertension. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH]
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Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]
Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excrete: To get rid of waste from the body. [NIH] Exfoliation: A falling off in scales or layers. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH]
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Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extrarenal: Outside of the kidney. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Facial: Of or pertaining to the face. [EU] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members. [NIH]
Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Practice: A medical specialty concerned with the provision of continuing, comprehensive primary health care for the entire family. [NIH] Farnesyl: Enzyme which adds 15 carbon atoms to the Ras precursor protein. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue,
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often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femoral Vein: The vein accompanying the femoral artery in the same sheath; it is a continuation of the popliteal vein and becomes the external iliac vein. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetal Death: Death of the young developing in utero. [NIH] Fetal Growth Retardation: The failure of a fetus to attain its expected growth potential at any gestational stage. [NIH] Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (heart/embryology) only on the basis of time. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic
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(blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fish Oils: Oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the livers. Those from the liver are usually high in vitamin A. The oils are used as dietary supplements, in soaps and detergents, as protective coatings, and as a base for other food products such as vegetable shortenings. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fludarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH]
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Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma-Endorphin: An endogenous opioid peptide derived from the pro-opiomelanocortin precursor peptide. It differs from alpha-endorphin by one amino acid. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Dosage: The number of copies of a given gene present in a cell or nucleus. An increase in gene dosage can result in the formation of higher levels of gene product, provided that
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the gene is not subject to autogenous regulation. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germinal Center: The activated center of a lymphoid follicle in secondary lymphoid tissue where B-lymphocytes are stimulated by antigens and helper T cells (T-lymphocytes, helperinducer) are stimulated to generate memory cells. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV
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virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulonephritis, Membranous: A disease of the glomerulus manifested clinically by proteinuria, and sometimes by other features of the nephrotic syndrome. It is histologically characterized by deposits in the glomerular capillary wall between the epithelial cell and the basement membrane and a thickening of the membrane. Also characteristic are outward projections of the membrane between the epithelial deposits in the form of "spikes". There is some agreement that the deposits are antigen-antibody complexes. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
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Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of
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neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanine: One of the four DNA bases. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
Haematological: Relating to haematology, that is that branch of medical science which treats of the morphology of the blood and blood-forming tissues. [EU] Haematology: The science of the blood, its nature, functions, and diseases. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Halitosis: An offensive, foul breath odor resulting from a variety of causes such as poor oral hygiene, dental or oral infections, or the ingestion of certain foods. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs,
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and access to medical care. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoietic growth factors: A group of proteins that cause blood cells to grow and mature. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Hematuria: Presence of blood in the urine. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemiplegia: Severe or complete loss of motor function on one side of the body. This condition is usually caused by BRAIN DISEASES that are localized to the cerebral hemisphere opposite to the side of weakness. Less frequently, BRAIN STEM lesions; cervical spinal cord diseases; peripheral nervous system diseases; and other conditions may manifest as hemiplegia. The term hemiparesis (see paresis) refers to mild to moderate weakness involving one side of the body. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH]
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Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatomegaly: Enlargement of the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpetiformis: Duhring's disease a recurring, inflammatory disease of the skin of unknown etiology characterized by erythematous, papular, pustular, or vesicular lesions which tend to group and are accompanied by itching and burning. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hiatal Hernia: A small opening in the diaphragm that allows the upper part of the stomach to move up into the chest. Causes heartburn from stomach acid flowing back up through the opening. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] High blood cholesterol: Cholesterol is the most abundant steroid in animal tissues, especially in bile and gallstones. The relationship between the intake of cholesterol and its manufacture by the body to its utilization, sequestration, or excretion from the body is called the cholesterol balance. When cholesterol accumulates, the balance is positive; when it declines, the balance is negative. In 1993, the NHLBI National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults issued an updated set of recommendations for monitoring and treatment of blood cholesterol levels. The NCEP guidelines recommended that total cholesterol levels and subfractions of high-density lipoprotein (HDL) cholesterol be measured beginning at age 20 in all adults, with subsequent periodic screenings as needed. Even in the group of patients at lowest risk for coronary heart disease (total cholesterol 200 mg/dL and HDL 35 mg/dL), the NCEP recommended that rescreening take place at least once every 5 years or upon physical examination. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histiocytic Necrotizing Lymphadenitis: Development of lesions in the lymph node
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characterized by infiltration of the cortex or paracortex by large collections of proliferating histiocytes and complete or, more often, incomplete necrosis of lymphoid tissue. [NIH] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homicide: The killing of one person by another. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]
Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [NIH] Human Genome Project: A coordinated effort of researchers to map and sequence the human genome. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH]
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Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypesthesia: Absent or reduced sensitivity to cutaneous stimulation. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypogammaglobulinemia: The most common primary immunodeficiency in which
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antibody production is deficient. [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Idiotype: The unique antigenic determinant in the variable region. [NIH] Ileitis: Inflammation of the ileum. [EU] Ileum: The lower end of the small intestine. [NIH] Iliac Vein: A vein on either side of the body which is formed by the union of the external and internal iliac veins and passes upward to join with its fellow of the opposite side to form the inferior vena cava. [NIH] Iloprost: An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of epoprostenol, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation. [NIH] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH]
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Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]
Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunologic Diseases: Disorders caused by abnormal or absent immunologic mechanisms, whether humoral, cell-mediated or both. [NIH] Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH]
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Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indolent: A type of cancer that grows slowly. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Infertility: The diminished or absent ability to conceive or produce an offspring while
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sterility is the complete inability to conceive or produce an offspring. [NIH] Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant
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monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-15: Cytokine that stimulates the proliferation of T-lymphocytes and shares biological activities with IL-2. IL-15 also can induce B-lymphocyte proliferation and differentiation. [NIH] Interleukin-18: Cytokine which resembles IL-1 structurally and IL-12 functionally. It enhances the cytotoxic activity of NK cells and CTLs, and appears to play a role both as neuroimmunomodulator and in the induction of mucosal immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy,
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implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intracranial Pressure: Pressure within the cranial cavity. It is influenced by brain mass, the circulatory system, CSF dynamics, and skull rigidity. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ionomycin: A divalent calcium ionophore that is widely used as a tool to investigate the role of intracellular calcium in cellular processes. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation;
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those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isoniazid: Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]
Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Joint Capsule: The sac enclosing a joint. It is composed of an outer fibrous articular capsule and an inner synovial membrane. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keloid: A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (cicatrix, hypertrophic) in that the former does not spread to surrounding tissues. [NIH] Keratectomy: The surgical removal of corneal tissue. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratoconjunctivitis Sicca: Drying and inflammation of the conjunctiva as a result of insufficient lacrimal secretion. When found in association with xerostomia and polyarthritis, it is called Sjogren's syndrome. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH]
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Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue. [NIH] Kidney Pelvis: The flattened, funnel-shaped expansion connecting the ureter to the kidney calices. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laboratory Personnel: Those health care professionals, technicians, and assistants staffing a research or health care facility where specimens are grown, tested, or evaluated and the results of such measures are recorded. [NIH] Lacrimal: Pertaining to the tears. [EU] Lactation: The period of the secretion of milk. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leflunomide: An anticancer drug that works by inhibiting a cancer cell growth factor. Also called SU101. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils,
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and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoencephalopathy: A condition with spongy holes in the brain's white matter. [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a
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correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Lod: The lowest analyte content which, if actually present, will be detected with reasonable statistical certainty and can be identified according to the identification criteria of the method. If both accuracy and precision are constant over a concentration range. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumbar puncture: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a spinal tap. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU]
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Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lupus Erythematosus, Systemic: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. [NIH] Lupus Nephritis: Glomerulonephritis associated with systemic lupus erythematosus. It is classified into four histologic types: mesangial, focal, diffuse, and membranous. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphadenitis: Inflammation of the lymph nodes. [NIH] Lymphadenopathy: Disease or swelling of the lymph nodes. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokine: A soluble protein produced by some types of white blood cell that stimulates other white blood cells to kill foreign invaders. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphopenia: Reduction in the number of lymphocytes. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes
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dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malar: Paired facial bones that help form the lateral und lower orbita. [NIH] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mange: Sarcoptic infestation of human skin, particularly a contagious skin disease caused by invasion of the epidermis with Sarcoptes scabiei. [NIH] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked
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by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Marital Status: A demographic parameter indicating a person's status with respect to marriage, divorce, widowhood, singleness, etc. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicine, Kampo: System of herbal medicine practiced in Japan by both herbalists and practitioners of modern medicine. Kampo originated in China and is based on Chinese herbal medicine (medicine, Chinese traditional). [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menarche: The establishment or beginning of the menstrual function. [EU]
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Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] Methoxychlor: An insecticide. Methoxychlor has estrogenic effects in mammals, among other effects. [NIH]
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Methyldopa: An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent. Before its alphaadrenergic actions became clear, methyldopa was thought to act by inhibiting decarboxylation of DOPA leading to depletion of norepinephrine or by conversion to and release as the false transmitter alpha-methylnorepinephrine. [NIH] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]
labeled
with
Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]
antibiotic
effective
against
tetracycline-resistant
Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family
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whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mixed Connective Tissue Disease: A syndrome with overlapping clinical features of systemic lupus erythematosus, scleroderma, polymyositis, and Raynaud's phenomenon. The disease is differentially characterized by high serum titers of antibodies to ribonucleasesensitive extractable (saline soluble) nuclear antigen and a "speckled" epidermal nuclear staining pattern on direct immunofluorescence. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer
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detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Monokines: Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]
Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiparous: 1. Having had two or more pregnancies which resulted in viable fetuses. 2. Producing several ova or offspring at one time. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are
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characterized by progressive degeneration of skeletal muscles. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagenic: Inducing genetic mutation. [EU] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelitis: Inflammation of the spinal cord. Relatively common etiologies include infections; autoimmune diseases; spinal cord; and ischemia (see also spinal cord vascular diseases). Clinical features generally include weakness, sensory loss, localized pain, incontinence, and other signs of autonomic dysfunction. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myositis: Inflammation of a voluntary muscle. [EU] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense
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pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neopterin: A pteridine derivative present in body fluids; elevated levels result from immune system activation, malignant disease, allograft rejection, and viral infections. (From Stedman, 26th ed) Neopterin also serves as a precursor in the biosynthesis of biopterin. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrology: A subspecialty of internal medicine concerned with the anatomy, physiology, and pathology of the kidney. [NIH] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH]
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Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuromyelitis Optica: A self-limiting, demyelinating disease of the optic nerves, the optic chiasm, and the spinal cord characterized by bilateral retrobulbar neuritis, usually accompanied by papillitis and transverse myelitis. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurosyphilis: A late form of syphilis that affects the brain and may lead to dementia and death. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between
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individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleic Acid Probes: Nucleic acid which complements a specific mRNA or DNA molecule, or fragment thereof; used for hybridization studies in order to identify microorganisms and for genetic studies. [NIH] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleolus Organizer Region: The chromosome region which is active in nucleolus formation and which functions in the synthesis of ribosomal RNA. [NIH] Nucleoprotein: Chromosomes consist largely of nuclei acids and proteins, joined here as complexes called nucleoproteins. [NIH] Nucleosomes: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH]
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Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Obstetrics: A medical-surgical specialty concerned with management and care of women during pregnancy, parturition, and the puerperium. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Onychomycosis: Mycosis of the nails, possibly due to some extent to humidity. [NIH] Oophorectomy: Surgery to remove one or both ovaries. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmologic: Pertaining to ophthalmology (= the branch of medicine dealing with the eye). [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Ophthalmoplegia: Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. [NIH] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes
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currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic disc: The circular area (disc) where the optic nerve connects to the retina. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic Nerve Diseases: Conditions which produce injury or dysfunction of the second cranial or optic nerve, which is generally considered a component of the central nervous system. Damage to optic nerve fibers may occur at or near their origin in the retina, at the optic disk, or in the nerve, optic chiasm, optic tract, or lateral geniculate nuclei. Clinical manifestations may include decreased visual acuity and contrast sensitivity, impaired color vision, and an afferent pupillary defect. [NIH] Optic Neuritis: Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [NIH]
Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but
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from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovariectomy: The surgical removal of one or both ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovulation Induction: Techniques for the artifical induction of ovulation. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH]
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Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Panniculitis: General term for inflammation of adipose tissue, usually of the skin, characterized by reddened subcutaneous nodules. [NIH] Papilledema: Swelling around the optic disk. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Paralysis: Loss of ability to move all or part of the body. [NIH] Paraparesis: Mild to moderate loss of bilateral lower extremity motor function, which may be a manifestation of spinal cord diseases; peripheral nervous system diseases; muscular diseases; intracranial hypertension; parasagittal brain lesions; and other conditions. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Partial Thromboplastin Time: Test of the intrinsic (factors VIII, IX, XI, and XII) and common (fibrinogen, prothrombin, factors V and X) pathways of coagulation in which a
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mixture of plasma and phospholipid platelet substitute (e.g., crude cephalins, soybean phosphatides) is recalcified and the time required for the appearance of fibrin strands measured. Activation may be provided by contact with the glass tube or exposure to activators (e.g., ellagic acid, particulate silicates such as diatomaceous earth or kaolin) before addition of the calcium chloride. It is used as a screening test and to monitor heparin therapy. [NIH] Parturition: The act or process of given birth to a child. [EU] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Care Team: Care of patients by a multidisciplinary team usually organized under the leadership of a physician; each member of the team has specific responsibilities and the whole team contributes to the care of the patient. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pemphigus: Group of chronic blistering diseases characterized histologically by acantholysis and blister formation within the epidermis. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and
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pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perennial: Lasting through the year of for several years. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering
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the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH]
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Photoallergy: Sensitization of the skin to light usually due to the action of certain substances or drugs, may occur shortly after exposure to a substance or after a latent period of from days to months. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]
Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Pilot Projects: Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placebos: Any dummy medication or treatment. Although placebos originally were medicinal preparations having no specific pharmacological activity against a targeted condition, the concept has been extended to include treatments or procedures, especially those administered to control groups in clinical trials in order to provide baseline measurements for the experimental protocol. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Placental Insufficiency: Failure of the placenta to deliver an adequate supply of nutrients and oxygen to the fetus. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plant Oils: Oils derived from plants or plant products. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized
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destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Exchange: Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (PPF), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Plateletpheresis: The preparation of platelet concentrates with the return of red cells and platelet-poor plasma to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the
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interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleurisy: Inflammation of the pleura, with exudation into its cavity and upon its surface. It may occur as either an acute or a chronic process. In acute pleurisy the pleura becomes reddened, then covered with an exudate of lymph, fibrin, and cellular elements (the dry stage); the disease may progress to the second stage, in which a copious exudation of serum occurs (stage of liquid effusion). The inflamed surfaces of the pleura tend to become united by adhesions, which are usually permanent. The symptoms are a stitch in the side, a chill, followed by fever and a dry cough. As effusion occurs there is an onset of dyspnea and a diminution of pain. The patient lies on the affected side. [EU] Pneumoconiosis: Condition characterized by permanent deposition of substantial amounts of particulate matter in the lungs, usually of occupational or environmental origin, and by the tissue reaction to its presence. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarteritis Nodosa: A form of necrotizing vasculitis involving small- and medium-sized arteries. The signs and symptoms result from infarction and scarring of the affected organ system. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polyethylene Glycols: Alpha-Hydro-omega-hydroxypoly(oxy-1,2-ethanediyls). Additional polymers of ethylene oxide and water and their ethers. They vary in consistency from liquid to solid, depending on the molecular weight, indicated by a number following the name. Used as surfactants in industry, including foods, cosmetics and pharmaceutics; in biomedicine, as dispersing agents, solvents, ointment and suppository bases, vehicles, tablet excipients. Some specific groups are lauromagrogols, nonoxynols, octoxynols and poloxamers. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their
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complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyradiculoneuropathy: Diseases characterized by injury or dysfunction involving multiple peripheral nerves and nerve roots. The process may primarily affect myelin or nerve axons. Two of the more common demyelinating forms are acute inflammatory polyradiculopathy (Guillain-Barre syndrome) and polyradiculoneuropathy, chronic inflammatory demyelinating. Polyradiculoneuritis refers to inflammation of multiple peripheral nerves and spinal nerve roots. [NIH] Polyradiculopathy: Disease or injury involving multiple spinal nerve roots. Polyradiculitis refers to inflammation of multiple spinal nerve roots. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Popliteal: Compression of the nerve at the neck of the fibula. [NIH] Popliteal Vein: The vein formed by the union of the anterior and posterior tibial veins; it courses through the popliteal space and becomes the femoral vein. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postnatal Care: The care provided a woman following the birth of a child. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH]
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Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Prasterone: A naturally occurring androgen isolated from urine. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Pregnenolone: Steroid hormone. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Care: Care provided the pregnant woman in order to prevent complications, and decrease the incidence of maternal and prenatal mortality. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other
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drugs, has been used as an adjunct to antibacterial therapy. [NIH] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Procainamide: A derivative of procaine with less CNS action. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Prolapse: The protrusion of an organ or part of an organ into a natural or artificial orifice. [NIH]
Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Proneness: Susceptibility to accidents due to human factors. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU]
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Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin Endoperoxides: Precursors in the biosynthesis of prostaglandins and thromboxanes from arachidonic acid. They are physiologically active compounds, having effect on vascular and airway smooth muscles, platelet aggregation, etc. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protective Clothing: Clothing designed to protect the individual against possible exposure to known hazards. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH]
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Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Prothrombin Time: Measurement of clotting time of plasma recalcified in the presence of excess tissue thromboplastin. Factors measured are fibrinogen, prothrombin, and factors V, VII, and X. It is used for monitoring anticoagulant therapy with coumarins. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pseudotumor Cerebri: A condition marked by raised intracranial pressure and characterized clinically by headaches; nausea; papilledema, peripheral constriction of the visual fields, transient visual obscurations, and pulsatile tinnitus. Obesity is frequently associated with this condition, which primarily affects women between 20 and 44 years of
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age. Chronic papilledema may lead to optic nerve injury (optic nerve diseases) and visual loss (blindness). [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]
Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Puerperium: Period from delivery of the placenta until return of the reproductive organs to their normal nonpregnant morphologic state. In humans, the puerperium generally lasts for six to eight weeks. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are
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known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quackery: The fraudulent misrepresentation of the diagnosis and treatment of disease. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation Chimera: An organism whose body contains cell populations of different genotypes as a result of the transplantation of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH]
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Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Rarefaction: The reduction of the density of a substance; the attenuation of a gas. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Antigen: Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU]
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Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relaxation Techniques: The use of muscular relaxation techniques in treatment. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Remission Induction: Therapeutic act or process that initiates a response to a complete or partial remission level. [NIH] Renal capsule: The fibrous connective tissue that surrounds each kidney. [NIH] Renal cell carcinoma: A type of kidney cancer. [NIH]
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Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Renal tubular acidosis: A rare disorder in which structures in the kidney that filter the blood are impaired, producing using that is more acid than normal. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative
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enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrobulbar: Behind the pons. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Reverberant: The sound field prevailing in a large enclosure with moderately reflecting surfaces. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rheumatology: A subspecialty of internal medicine concerned with the study of inflammatory or degenerative processes and metabolic derangement of connective tissue
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structures which pertain to a variety of musculoskeletal disorders, such as arthritis. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribonucleoproteins: Proteins conjugated with ribonucleic acids (RNA) or specific RNA. Many viruses are ribonucleoproteins. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosomal Proteins: Proteins found in ribosomes. They are believed to have a catalytic function in reconstituting biologically active ribosomal subunits. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rituximab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Ruminants: A suborder of the order Artiodactyla whose members have the distinguishing feature of a four-chambered stomach. Horns or antlers are usually present, at least in males. [NIH]
Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility. [NIH]
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Salmonellosis: Infection by salmonellae. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Sclerotic: Pertaining to the outer coat of the eye; the sclera; hard, indurated or sclerosed. [NIH]
Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH]
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Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selection Bias: The introduction of error due to systematic differences in the characteristics between those selected and those not selected for a given study. In sampling bias, error is the result of failure to ensure that all members of the reference population have a known chance of selection in the sample. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serositis: Inflammation of a serous membrane. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system,
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gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Sex Hormone-Binding Globulin: A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosacaccharide modifications. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Sicca: Failure of lacrimal secretion, keratoconjunctivitis sicca, failure of secretion of the salivary glands and mucous glands of the upper respiratory tract and polyarthritis. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoid Colon: The lower part of the colon that empties into the rectum. [NIH] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by
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a physician, or subjective when perceived by the patient. [NIH] Silicosis: A type of pneumoconiosis caused by inhalation of particles of silica, quartz, ganister or slate. [NIH] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin graft: Skin that is moved from one part of the body to another. [NIH] Skin test: A test for an immune response to a compound by placing it on or under the skin. [NIH]
Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Security: Government sponsored social insurance programs. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Socioeconomic Factors: Social and economic factors that characterize the individual or group within the social structure. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other
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diseases. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Diseases: Pathologic conditions which feature spinal cord damage or dysfunction, including disorders involving the meninges and perimeningeal spaces surrounding the spinal cord. Traumatic injuries, vascular diseases, infections, and inflammatory/autoimmune processes may affect the spinal cord. [NIH] Spinal Cord Vascular Diseases: Hypoxic-ischemic and hemorrhagic disorders of the spinal cord. Arteriosclerosis, emboli, and vascular malformations are potential causes of these conditions. [NIH] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [NIH] Spinal tap: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a lumbar puncture. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes,
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filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenectomy: An operation to remove the spleen. [NIH] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [NIH] Splenomegaly: Enlargement of the spleen. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] Status Epilepticus: Repeated and prolonged epileptic seizures without recovery of consciousness between attacks. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Steroid therapy: Treatment with corticosteroid drugs to reduce swelling, pain, and other symptoms of inflammation. [NIH] Stillbirth: The birth of a dead fetus or baby. [NIH]
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Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress management: A set of techniques used to help an individual cope more effectively with difficult situations in order to feel better emotionally, improve behavioral skills, and often to enhance feelings of control. Stress management may include relaxation exercises, assertiveness training, cognitive restructuring, time management, and social support. It can be delivered either on a one-to-one basis or in a group format. [NIH] Stress urinary: Leakage of urine caused by actions--such as coughing, laughing, sneezing, running, or lifting--that place pressure on the bladder from inside the body. Stress urinary incontinence can result from either a fallen bladder or weak sphincter muscles. [NIH] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Stria Vascularis: A layer of highly vascular pigmented granular cells on the outer wall of the cochlear duct. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
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Substrate: A substance upon which an enzyme acts. [EU] Subungual: Beneath a nail. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppository: A medicated mass adapted for introduction into the rectal, vaginal, or urethral orifice of the body, suppository bases are solid at room temperature but melt or dissolve at body temperature. Commonly used bases are cocoa butter, glycerinated gelatin, hydrogenated vegetable oils, polyethylene glycols of various molecular weights, and fatty acid esters of polyethylene glycol. [EU] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Cyst: A nodular, tumorlike lesion in or about a tendon sheath or joint capsule, especially of the hands, wrists, or feet. It is not a true cyst as it lacks an epithelial wall, and it does not communicate with the underlying synovial space. The lesion represents a focal accumulation of mucin in the dermis of the dorsal aspect of the distal phalanges or, less often, other portions of the extremities. [NIH] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Syphilis Serodiagnosis: Serologic tests for syphilis. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH]
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Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systemic therapy: Treatment that uses substances that travel through the bloodstream, reaching and affecting cells all over the body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH]
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Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thromboembolism: Obstruction of a vessel by a blood clot that has been transported from a distant site by the blood stream. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombopenia: Reduction in the number of platelets in the blood. [NIH] Thromboplastin: Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. [NIH] Thrombopoietin: A humoral factor that controls blood platelet production through stimulation of megakaryocyte populations. Bone marrow megakaryocytes increase in both size and number in response to exposure to thrombopoietin. [NIH] Thromboses: The formation or presence of a blood clot within a blood vessel during life. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment
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of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Time Management: Planning and control of time to improve efficiency and effectiveness. [NIH]
Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Extracts: Preparations made from animal tissues or organs; they usually contain many components, any one of which may be pharmacologically or physiologically active; extracts may contain specific, but uncharacterized factors or proteins with specific actions. [NIH]
T-lymphocyte: Cell which develops in the thymus and which acts to help or suppress T and B cell function (antibody production) and which is the effector (cytotoxic) cell of cellmediated immunity. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tome: A zone produced by a number of irregular spaces contained in the outermost layer of denture of the root of a tooth. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonsils: Small masses of lymphoid tissue on either side of the throat. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the
530 Lupus
bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]
Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein
Dictionary 531
through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Trypsin Inhibitors: Serine proteinase inhibitors which inhibit trypsin. They may be endogenous or exogenous compounds. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubal ligation: An operation to tie the fallopian tubes closed. This procedure prevents pregnancy by blocking the passage of eggs from the ovaries to the uterus. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculin: A sterile liquid containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis. [NIH]
Tuberculostatic: Inhibiting the growth of Mycobacterium tuberculosis. [EU] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]
Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is
532 Lupus
also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Ultrasound test: A test that bounces sound waves off tissues and internal organs and changes the echoes into pictures (sonograms). [NIH] Ultraviolet radiation: Invisible rays that are part of the energy that comes from the sun. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH]
Dictionary 533
Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urogenital Diseases: Diseases of the urogenital tract. [NIH] Urologic Diseases: Diseases of the urinary tract in both male and female. It does not include the male genitalia for which urogenital diseases is used for general discussions of diseases of both the urinary tract and the genitalia. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Insufficiency: Inadequacy of the venous valves and impairment of venous return (venous stasis) usually from the legs, often with edema and sometimes with stasis ulcers at the ankle. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH]
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Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Core Proteins: Proteins found mainly in icosahedral DNA and RNA viruses. They consist of proteins directly associated with the nucleic acid inside the nucleocapsid. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viral Proteins: Proteins found in any species of virus. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Void: To urinate, empty the bladder. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH]
Dictionary 535
White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
537
INDEX A Abdominal, 121, 234, 362, 376, 429, 456, 467, 489, 500, 502, 503, 517, 532 Abdominal Pain, 234, 376, 429, 467, 503, 532 Aberrant, 40, 64, 73, 81, 85, 88, 97, 429 Ablation, 66, 296, 429 Abortion, 425, 429, 436, 508 Abscess, 131, 227, 230, 429 Acantholysis, 429, 501 Acatalasia, 429, 445 Acceptor, 429, 484, 499, 530 Acetaminophen, 408, 429 Acetylcholine, 429, 495 Acetylgalactosamine, 429, 470 Acetylglucosamine, 429, 470 Acidity, 285, 429, 503 Acidosis, 429 Acne, 374, 429 Actin, 429, 430, 493 Actinin, 18, 430 Activated Protein C Resistance, 240, 430 Acute Disease, 114, 430 Acute leukemia, 154, 266, 299, 430 Acute lymphoblastic leukemia, 269, 430 Acute lymphocytic leukemia, 430 Acute renal, 266, 390, 430, 472 Adaptability, 430, 445 Adaptation, 17, 122, 430, 447 Adenine, 430, 513 Adenoma, 137, 430 Adenosine, 81, 125, 430, 503 Adhesions, 430, 506 Adipose Tissue, 430, 484, 500 Adjustment, 17, 83, 291, 292, 430 Adjuvant, 72, 318, 430, 467 Adolescence, 13, 430 Adoptive Transfer, 48, 80, 103, 105, 106, 333, 430 Adrenal Cortex, 431, 453, 463, 509, 516 Adrenal Glands, 336, 431 Adrenal insufficiency, 4, 431 Adrenergic, 431, 435, 436, 457, 462, 490, 513 Adverse Effect, 7, 15, 70, 306, 431, 503, 521 Aerobic, 156, 376, 431 Afferent, 431, 498, 523
Affinity, 19, 23, 43, 65, 74, 77, 79, 110, 151, 431, 484, 522 Agar, 431, 477, 504 Agarose, 431, 477 Age of Onset, 63, 431 Agonist, 431, 457, 490 Albumin, 390, 431, 505, 526 Albuminuria, 225, 431 Aldehydes, 343, 432 Algorithms, 432, 441 Alimentary, 432, 500, 501 Alkaline, 429, 432, 433, 443 Alkalinization, 213, 432 Alkaloid, 432, 513 Alkylating Agents, 432, 447 Alleles, 8, 46, 48, 53, 87, 170, 174, 267, 432, 484 Allograft, 195, 223, 258, 432, 494 Allylamine, 432, 433 Alopecia, 45, 190, 432, 454 Alpha 1-Antitrypsin, 335, 432 Alpha Particles, 432, 513 Alternative medicine, 283, 350, 373, 432 Ambulatory Care, 432 Ameliorating, 20, 432 Amenorrhea, 8, 216, 432 Amine, 178, 432 Amino Acid Motifs, 433, 451 Amino Acid Sequence, 77, 324, 327, 433, 434, 435, 450, 451, 463, 468, 509, 521 Amino-terminal, 127, 433 Ammonia, 432, 433 Amniotic Fluid, 433, 468 Amplification, 45, 46, 433 Amyloid, 122, 233, 270, 433 Anaemia, 143, 433 Anaerobic, 433, 493, 518, 524 Anaesthesia, 433, 478 Anal, 36, 60, 108, 250, 257, 433, 485 Analgesic, 429, 433, 461, 513 Analog, 329, 332, 433, 476 Analogous, 433, 458, 530 Analytes, 398, 433 Anaphylatoxins, 434, 450 Anaplasma, 317, 434 Anaplasmosis, 434 Anatomical, 434, 438, 447, 460, 477, 519 Androgen-Binding Protein, 434, 521
538 Lupus
Androgenic, 303, 434, 454 Androgens, 336, 338, 431, 434, 453 Anemia, 87, 111, 115, 127, 155, 303, 317, 319, 325, 343, 376, 393, 394, 434, 441, 487 Anergy, 22, 33, 69, 74, 80, 128, 358, 434 Anesthesia, 201, 434, 435, 509 Aneurysm, 207, 213, 247, 434, 437, 533 Angiitis, 10, 434 Angiogenesis, 434, 488 Animal model, 20, 37, 38, 72, 78, 79, 87, 90, 99, 109, 267, 282, 298, 332, 434 Anionic, 156, 434 Anions, 431, 434, 481, 508, 521 Ankle, 434, 533 Annealing, 434, 506 Anomalies, 74, 434 Antecedent, 109, 435 Anti-Anxiety Agents, 435, 508 Antibacterial, 318, 435, 482, 509, 523 Antibiotic, 4, 10, 46, 57, 435, 448, 462, 490, 508, 523, 527 Antibiotic Prophylaxis, 4, 57, 435, 508 Antibodies, 7, 8, 12, 13, 16, 18, 19, 21, 22, 29, 32, 33, 39, 40, 42, 48, 50, 55, 65, 66, 67, 72, 74, 77, 78, 84, 87, 88, 89, 95, 97, 100, 102, 103, 104, 105, 108, 110, 114, 116, 123, 124, 125, 126, 129, 135, 139, 143, 147, 150, 151, 153, 154, 158, 159, 160, 168, 174, 184, 189, 195, 204, 205, 209, 221, 231, 237, 238, 240, 254, 256, 267, 270, 272, 294, 295, 298, 304, 306, 311, 317, 319, 321, 322, 324, 325, 326, 327, 328, 329, 330, 333, 334, 336, 337, 338, 339, 343, 344, 345, 347, 370, 371, 373, 399, 402, 412, 413, 426, 435, 436, 439, 471, 476, 477, 486, 491, 492, 505 Antibodies, Anticardiolipin, 435, 436 Antibodies, Antiphospholipid, 435, 436 Anticonvulsant, 44, 435, 503 Antiemetic, 435, 436, 447 Antifungal, 435, 522 Antigen-Antibody Complex, 435, 450, 469 Antigen-presenting cell, 105, 332, 436, 455 Antihypertensive, 436, 475, 490 Anti-infective, 436, 475 Anti-Inflammatory Agents, 10, 323, 436, 438, 453 Antimetabolite, 436, 489 Antineoplastic, 432, 436, 448, 453, 454, 489, 522 Antioxidant, 21, 85, 176, 230, 271, 436, 499
Antiphospholipid Syndrome, 14, 99, 126, 137, 139, 143, 150, 156, 174, 175, 176, 189, 194, 201, 209, 220, 245, 249, 273, 331, 338, 377, 379, 435, 436 Antipruritic, 12, 436 Antipsychotic, 436, 447 Antipyretic, 429, 436, 513 Antiserum, 436, 439, 453 Antiviral, 436, 480, 502 Anuria, 436, 482 Anus, 433, 436, 442, 449, 515 Anxiety, 354, 435, 437 Aorta, 207, 437, 452, 533 Aortic Aneurysm, 261, 437 Apheresis, 144, 173, 236, 256, 302, 437 Aplasia, 220, 303, 437 Apolipoproteins, 437, 484 Applicability, 122, 437 Approximate, 323, 327, 437 Aqueous, 437, 440, 454, 475, 483 Arachidonate 15-Lipoxygenase, 437, 485 Arachidonate Lipoxygenases, 437, 485 Arachidonic Acid, 437, 459, 476, 484, 510 Arginine, 95, 97, 222, 434, 437, 495, 531 Arterial, 10, 21, 35, 51, 132, 322, 331, 332, 432, 436, 437, 438, 444, 447, 475, 511, 527 Arteries, 334, 437, 438, 441, 452, 485, 490, 493, 506, 512, 528 Arterioles, 246, 437, 438, 441, 443 Arteriolosclerosis, 437, 438 Arteriosclerosis, 56, 437, 475, 523 Arteriovenous, 232, 438 Arteritis, 207, 303, 438 Artery, 100, 138, 171, 217, 233, 247, 309, 377, 434, 437, 438, 452, 453, 459, 465, 500, 512, 516 Arthralgia, 279, 325, 438 Arthritis, Rheumatoid, 113, 300, 360, 438 Arthropathy, 183, 438 Arthropod Vectors, 434, 438 Articular, 438, 482, 499 Aspartic, 92, 438, 460 Aspartic Acid, 92, 438 Aspergillosis, 182, 438 Aspiration, 307, 308, 438 Aspirin, 325, 350, 403, 438 Assay, 10, 24, 56, 102, 198, 226, 240, 275, 318, 324, 327, 329, 339, 438, 477, 514 Asymptomatic, 5, 51, 104, 129, 429, 438 Ataxia, 394, 438, 527 Atmospheric Pressure, 438, 475 Atrial, 227, 438
Index 539
Atrioventricular, 104, 293, 438 Atrium, 438, 533 Atrophy, 6, 14, 214, 255, 394, 429, 438 Atypical, 8, 32, 95, 347, 439, 478 Audiovisual Aids, 439 Auditory, 268, 439, 463 Autoimmune Hepatitis, 8, 197, 439 Autologous, 77, 239, 268, 296, 297, 303, 439 Autologous bone marrow transplantation, 268, 439 Autonomic, 132, 429, 436, 439, 493, 496, 502, 523 Avidity, 22, 46, 439 Axons, 439, 456, 498, 507, 523 B Bacillus, 223, 439, 531 Bacteremia, 4, 247, 439, 518 Bacteria, 13, 45, 298, 306, 318, 319, 336, 339, 413, 434, 435, 439, 440, 448, 455, 459, 461, 462, 465, 467, 470, 490, 493, 518, 520, 523, 524, 530, 532, 533 Bacterial Infections, 439, 450 Bacterial Physiology, 430, 439 Bacteriophage, 439, 505, 518, 530 Bacterium, 318, 439, 472 Bacteriuria, 439, 532 Barbiturate, 439, 528 Basal Ganglia, 272, 436, 438, 440, 467, 476 Basal Ganglia Diseases, 438, 440, 476 Base, 240, 316, 430, 440, 454, 455, 456, 463, 466, 468, 482, 496, 506, 527 Basement Membrane, 94, 143, 319, 440, 464, 469, 483 Basophils, 440, 470, 483 Benign, 192, 316, 430, 437, 440, 454, 467, 471, 494, 514, 518 Beta-pleated, 433, 440 Bilateral, 129, 231, 233, 440, 495, 500, 517 Bile, 362, 440, 447, 467, 473, 474, 482, 485, 524 Bile Acids, 440, 524 Bile Acids and Salts, 440 Bile duct, 362, 440, 447, 467 Bile Pigments, 440, 482 Biliary, 105, 362, 440 Bilirubin, 431, 440, 467, 475 Binding Sites, 75, 102, 317, 440 Biological response modifier, 440, 441, 480 Biological therapy, 440, 471 Biopsy specimen, 9, 301, 441 Biopterin, 441, 494
Biotechnology, 13, 114, 118, 360, 373, 389, 392, 393, 394, 395, 441 Biotransformation, 441 Bladder, 6, 299, 311, 362, 441, 451, 454, 478, 492, 510, 525, 532, 534 Blastocyst, 441, 451, 460, 504 Blister, 441, 501 Bloating, 441, 478 Blood Coagulation, 19, 121, 189, 266, 321, 331, 334, 441, 443, 528 Blood Coagulation Factors, 441 Blood Platelets, 377, 441, 488, 521, 528 Blood pressure, 7, 16, 297, 343, 362, 364, 425, 436, 441, 444, 475, 491, 512, 522 Blood Proteins, 294, 299, 441 Blood Viscosity, 152, 441 Blot, 18, 54, 327, 441 Body Burden, 24, 442 Body Fluids, 328, 330, 442, 458, 494, 522 Body Image, 377, 442 Bone Marrow Cells, 318, 442, 471, 488 Bone Marrow Transplantation, 66, 103, 122, 442 Bone metastases, 442, 448 Bone scan, 301, 442, 519 Bowel, 119, 223, 232, 346, 362, 376, 433, 442, 456, 479, 481, 483, 503, 525, 532 Bowel Movement, 442, 456, 525 Brachytherapy, 442, 480, 481, 513, 535 Bradykinin, 442, 495, 505 Brain Stem, 442, 446 Branch, 322, 421, 442, 471, 477, 486, 495, 497, 501, 523, 528 Breakdown, 341, 442, 456, 467, 498 Breeding, 37, 53, 442 Buccal, 442, 486 Bullous, 131, 196, 220, 268, 442 Bypass, 52, 138, 442 C Calcifediol, 442, 443 Calcification, 212, 438, 443 Calcineurin, 44, 443 Calcinosis, 131, 157, 443 Calcitriol, 259, 443 Calcium, 26, 39, 443, 448, 450, 475, 481, 488, 490, 500, 501, 511, 521 Calcium Chloride, 443, 501 Calibration, 334, 443 Calmodulin, 143, 443 Candidiasis, 147, 375, 443 Candidosis, 443 Capillary, 442, 443, 469, 484, 534
540 Lupus
Capsid, 74, 117, 444, 496 Capsules, 444, 467, 469 Captopril, 16, 444 Carbohydrate, 444, 453, 469, 470, 507 Carbon Dioxide, 444, 455, 504, 516 Carcinogenic, 432, 444, 479, 509, 524 Carcinogens, 444, 493, 497, 499 Carcinoma, 143, 331, 444 Cardiac, 3, 10, 14, 85, 104, 132, 208, 390, 432, 444, 460, 462, 463, 467, 493, 513, 524, 526 Cardiolipins, 338, 436, 444 Cardiopulmonary, 9, 351, 400, 444 Cardiovascular disease, 35, 72, 100, 228, 364, 372, 377, 444, 485 Cardiovascular System, 350, 444 Carotene, 286, 444, 517 Carrier Proteins, 444, 505, 514 Case report, 125, 134, 136, 157, 177, 181, 182, 183, 202, 204, 208, 212, 223, 227, 237, 243, 247, 257, 265, 444, 448 Case series, 197, 444, 448 Caspase, 140, 181, 445 Catalase, 83, 429, 445 Cataracts, 299, 324, 445 Catheter, 295, 298, 308, 311, 445 Caudal, 445, 456, 476, 507 Causal, 64, 75, 81, 349, 445, 517 Cause of Death, 377, 445 Cell, 5, 6, 12, 16, 18, 22, 23, 25, 26, 28, 29, 31, 32, 33, 35, 37, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 51, 52, 53, 65, 66, 67, 68, 69, 70, 71, 73, 74, 75, 76, 77, 80, 81, 85, 89, 90, 92, 94, 95, 96, 97, 98, 101, 102, 103, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 116, 117, 124, 128, 141, 149, 152, 153, 154, 158, 166, 175, 176, 177, 185, 193, 195, 202, 218, 220, 222, 237, 241, 244, 278, 296, 297, 300, 303, 310, 311, 318, 320, 326, 327, 328, 329, 333, 340, 342, 343, 345, 347, 370, 376, 393, 394, 407, 429, 431, 434, 436, 437, 438, 439, 441, 443, 444, 445, 447, 448, 450, 454, 455, 456, 459, 460, 461, 463, 464, 465, 466, 467, 468, 469, 470, 471, 474, 476, 477, 479, 480, 481, 483, 486, 488, 491, 492, 493, 494, 495, 496, 497, 499, 500, 503, 504, 505, 507, 509, 510, 513, 514, 516, 518, 520, 521, 525, 527, 528, 529, 530, 531, 535 Cell Adhesion, 49, 70, 108, 152, 445 Cell Adhesion Molecules, 108, 445
Cell Death, 437, 445, 448, 469 Cell Differentiation, 445, 521 Cell Division, 327, 393, 439, 445, 471, 481, 491, 504, 520 Cell Extracts, 46, 445 Cell membrane, 345, 444, 445, 456, 503 Cell proliferation, 90, 112, 128, 438, 445, 480, 521 Cell Size, 445, 466 Cell Survival, 52, 77, 445, 471 Cell Transplantation, 296, 303, 445 Cellulitis, 200, 215, 445 Cellulose, 446, 466, 504 Centrifugation, 446, 490 Cerebellar, 178, 438, 446, 515, 531 Cerebellum, 64, 446, 515 Cerebral, 78, 99, 121, 133, 134, 209, 223, 255, 259, 260, 269, 276, 278, 279, 280, 331, 438, 440, 442, 446, 452, 462, 463, 472, 487, 527, 528 Cerebral Cortex, 438, 446, 463 Cerebrospinal, 174, 184, 192, 270, 298, 446, 485, 523 Cerebrospinal fluid, 174, 184, 192, 270, 298, 446, 485, 523 Cerebrovascular, 78, 440, 444, 446, 527 Cerebrum, 446, 527, 531 Cervical, 446, 472, 518 Cervix, 429, 446, 516 Chemokines, 70, 446 Chemotactic Factors, 446, 450 Chemotherapeutic agent, 89, 323, 446 Chemotherapy, 5, 127, 280, 355, 446 Chest Pain, 11, 446 Child Rearing, 365, 446 Chin, 149, 156, 175, 199, 201, 254, 265, 267, 268, 270, 271, 281, 283, 447, 489 Chlorambucil, 299, 447 Chlordecone, 24, 447 Chlorine, 447 Chloroquine, 155, 382, 447 Chlorpromazine, 332, 447 Cholangitis, 218, 447 Cholecalciferol, 257, 447 Cholesterol, 272, 284, 285, 305, 324, 336, 440, 447, 448, 453, 458, 467, 473, 475, 484, 485, 488, 524 Cholesterol Esters, 447, 484 Chorioretinitis, 447, 517 Choroid, 447, 516, 517 Chromaffin System, 447, 460
Index 541
Chromatin, 29, 38, 52, 62, 86, 95, 110, 111, 123, 239, 329, 437, 447, 496 Chromosomal, 53, 54, 64, 69, 81, 341, 433, 447, 517 Chronic Disease, 13, 17, 108, 355, 365, 401, 407, 409, 411, 447 Chronic granulocytic leukemia, 447, 448 Chronic myelogenous leukemia, 268, 448 Chronic renal, 5, 16, 226, 258, 448, 506 Chylomicrons, 448, 484 Cicatrix, 448, 482 Cicatrix, Hypertrophic, 448, 482 Cidofovir, 227, 448 Circulatory system, 448, 460, 481 Cirrhosis, 105, 448 CIS, 448, 517 Cladribine, 185, 448 Clarithromycin, 318, 448 Clinical Medicine, 124, 448, 508 Clinical Protocols, 112, 448 Clinical study, 360, 448, 452 Clodronate, 78, 448 Clonal Deletion, 23, 80, 448 Clone, 19, 449 Cloning, 32, 37, 54, 56, 87, 441, 449 Clot Retraction, 449, 505 Cochlear, 449, 525, 529 Cochlear Duct, 449, 525 Codon, 206, 449, 468 Cofactor, 19, 133, 449, 511, 528 Cognitive restructuring, 353, 449, 525 Colitis, 140, 182, 346, 347, 449 Collagen, 16, 94, 249, 354, 366, 433, 438, 440, 449, 451, 464, 465, 467, 482, 488, 505, 509 Collapse, 442, 449 Colloidal, 431, 449, 459, 521 Colon, 393, 449, 479, 483, 521, 532 Combination chemotherapy, 5, 449 Combination Therapy, 306, 449, 463 Combinatorial, 79, 449 Common Variable Immunodeficiency, 89, 450 Complement Activation, 20, 108, 434, 450 Complementarity Determining Regions, 116, 450 Complementary and alternative medicine, 265, 288, 450 Complementary medicine, 265, 450 Complementation, 46, 450 Complete remission, 6, 8, 193, 450, 515 Complete response, 450
Compliance, 277, 408, 451 Computational Biology, 389, 392, 451 Computed tomography, 121, 232, 248, 269, 279, 280, 451, 519 Computerized tomography, 27, 451 Concentric, 437, 451, 496 Conception, 406, 429, 451, 452, 465, 508, 522, 524 Concomitant, 125, 137, 222, 240, 269, 278, 451 Conduction, 99, 451 Cones, 451, 517 Congestion, 436, 451, 462 Conjugated, 271, 290, 297, 440, 451, 454, 496, 518 Conjunctiva, 451, 479, 482 Conjunctivitis, 146, 451 Connective Tissue Cells, 451 Connective Tissue Diseases, 14, 127, 179, 239, 355, 408, 436, 451 Consciousness, 433, 435, 451, 455, 457, 512, 524 Consensus Sequence, 79, 433, 451, 452 Conserved Sequence, 433, 451 Constipation, 362, 436, 452, 503 Constitutional, 319, 452, 493, 517 Constriction, 452, 482, 511 Consumption, 20, 86, 97, 232, 452, 467, 497, 516 Contraception, 4, 377, 402, 403, 452 Contractility, 452, 459 Contracture, 273, 452 Contraindications, ii, 452 Contrast Sensitivity, 452, 498 Control group, 7, 17, 44, 82, 452, 504 Controlled clinical trial, 53, 452, 514 Controlled study, 126, 172, 187, 452 Conventional therapy, 112, 452 Conventional treatment, 452 Convulsions, 435, 440, 452, 458, 508 Coordination, 36, 446, 452, 492 Corn Oil, 85, 452 Cornea, 452, 482, 519, 525, 535 Coronary, 18, 20, 35, 100, 138, 171, 217, 233, 247, 309, 331, 377, 444, 452, 453, 473, 490, 493 Coronary Artery Bypass, 20, 217, 452 Coronary heart disease, 18, 444, 452, 473 Coronary Thrombosis, 453, 490, 493 Cortex, 453, 461, 463, 474, 515 Cortical, 453, 463, 520, 527
542 Lupus
Corticosteroid, 11, 44, 100, 151, 163, 210, 308, 335, 453, 508, 524 Cortisol, 140, 431, 453 Cortisone, 406, 453, 456, 508 Coumarins, 453, 511 Cranial, 446, 453, 471, 481, 494, 498, 502 Creatine, 188, 453 Creatine Kinase, 188, 453 Creatinine, 8, 425, 453, 482 Criterion, 64, 453 Cross Reactions, 328, 453 Crossing-over, 453, 515 Curative, 336, 338, 453, 528 Cyclic, 107, 125, 140, 443, 454, 471, 495, 510 Cyclin, 80, 156, 454 Cyclophosphamide, 5, 6, 7, 9, 15, 20, 66, 89, 112, 136, 140, 151, 169, 176, 185, 188, 193, 201, 204, 211, 216, 229, 236, 243, 244, 245, 273, 296, 297, 299, 303, 304, 306, 307, 325, 335, 370, 372, 377, 382, 399, 405, 454 Cyclosporine, 5, 6, 7, 134, 299, 303, 454 Cyst, 119, 454, 526 Cystitis, 6, 362, 454 Cytarabine, 309, 333, 454 Cytidine, 333, 454 Cytochrome, 50, 454 Cytomegalovirus, 140, 202, 454 Cytopenia, 249, 454 Cytoplasm, 333, 437, 440, 445, 454, 462, 496, 518 Cytosine, 454, 513 Cytotoxicity, 75, 78, 89, 112, 432, 454 D Danazol, 187, 336, 454 Decarboxylation, 455, 490 Decidua, 455, 504 Decompression, 379, 455 Defense Mechanisms, 71, 455 Degenerative, 455, 473, 498, 517 Dehydration, 375, 455 Dehydroepiandrosterone, 61, 142, 254, 256, 286, 287, 301, 310, 335, 336, 338, 350, 383, 455 Deletion, 16, 22, 28, 69, 70, 73, 80, 109, 225, 437, 448, 455, 467 Delusions, 455, 512 Dementia, 79, 436, 455, 495 Denaturation, 455, 506 Dendrites, 455, 456 Dendritic, 42, 48, 146, 157, 455, 488
Dendritic cell, 42, 48, 146, 157, 455 Dental Care, 4, 455 Dental Caries, 375, 455 Dentate Gyrus, 455, 473 Dentists, 4, 456 Deoxyribonucleic, 11, 150, 349, 456, 518 Deoxyribonucleic acid, 11, 150, 349, 456, 518 Deoxyribonucleotides, 456 Depigmentation, 456, 534 Depolarization, 456, 521 Dermatitis, 456, 458 Dermatologist, 328, 456 Dermis, 456, 482, 526 Deuterium, 456, 475 Dexamethasone, 86, 104, 293, 294, 456 Diabetes Mellitus, 112, 231, 318, 390, 456, 469, 472 Diagnostic procedure, 315, 373, 456 Diaphragm, 456, 473, 505 Diarrhea, 362, 375, 456 Diastolic, 456, 475 Diencephalon, 456, 476, 527, 528 Diffusivity, 121, 456 Digestion, 432, 440, 442, 456, 458, 478, 481, 485, 501, 525 Digestive system, 314, 456 Digestive tract, 456, 522 Dihydrotestosterone, 456, 515, 521 Dilatation, 429, 434, 457, 508, 533 Diploid, 450, 457, 504 Discrete, 457, 527, 535 Discrimination, 266, 457 Disease Progression, 38, 66, 457, 534 Disease Susceptibility, 38, 47, 69, 89, 93, 457 Disposition, 48, 457 Dissection, 32, 56, 81, 89, 122, 233, 457 Dissociation, 47, 101, 104, 431, 457 Dissociative Disorders, 457 Distal, 24, 33, 67, 161, 452, 457, 511, 526 Docosahexaenoic Acids, 268, 457 Domesticated, 457, 471 Dopamine, 436, 447, 457, 495, 503 Dorsal, 457, 507, 523, 526 Double-blind, 97, 104, 142, 151, 172, 187, 244, 254, 457 Drug Design, 372, 383, 458 Drug Interactions, 382, 458 Drug Tolerance, 458, 529 Dry Eye Syndrome, 300, 458 Duct, 415, 458, 463, 518, 524
Index 543
Duodenum, 440, 458, 525 Dura mater, 458, 489, 499 Dyes, 433, 440, 458, 466 Dyslipidemia, 127, 258, 458 Dyspareunia, 458, 463 Dyspepsia, 458, 478 Dysplasia, 394, 458 Dyspnea, 458, 506 Dystrophy, 394, 458 E Echocardiography, 3, 458 Eclampsia, 458, 508 Ectopic, 42, 458 Eczema, 366, 458 Edema, 258, 424, 458, 481, 493, 494, 497, 508, 533 Effector, 46, 73, 75, 80, 101, 112, 199, 327, 337, 339, 429, 450, 459, 529 Effector cell, 112, 459 Efferent, 340, 434, 459, 523 Efferent Pathways, 340, 459 Effusion, 459, 506 Eicosanoids, 99, 212, 459 Ejection fraction, 104, 459 Elastic, 35, 459, 523 Elasticity, 35, 437, 459 Elastin, 35, 449, 451, 459, 464 Elective, 11, 459 Electrocardiogram, 295, 301, 306, 308, 459 Electrocoagulation, 449, 459 Electrolyte, 453, 459, 482, 490, 507, 522 Electrophoresis, 43, 91, 210, 459, 477 Ellagic Acid, 459, 501 Emboli, 299, 379, 459, 523 Embolus, 459, 478 Embryo, 429, 441, 445, 459, 478, 508, 524 Embryo Transfer, 459, 508 Embryology, 460, 465 Emollient, 460, 469, 497 Emphysema, 432, 460 Empirical, 14, 460 Empyema, 235, 460 Enamel, 455, 460 Encephalitis, 51, 278, 460 Encephalitis, Viral, 460 Encephalomyelitis, 41, 72, 460 Endemic, 195, 258, 460, 487, 524 Endocarditis, 3, 4, 175, 319, 343, 443, 460 Endocardium, 460 Endocrine Glands, 460 Endocrine System, 71, 460, 494 Endometriosis, 454, 460
Endometrium, 455, 460, 489 Endopeptidases, 460, 510 Endorphin, 461, 467 Endothelial cell, 49, 55, 67, 105, 153, 218, 460, 461, 528 Endothelium, 108, 461, 495, 505 Endothelium, Lymphatic, 461 Endothelium, Vascular, 461 Endothelium-derived, 461, 495 Endotoxic, 461, 484 Endotoxin, 71, 461, 531 End-stage renal, 9, 269, 448, 461, 506 Enteropeptidase, 461, 531 Entorhinal Cortex, 461, 473 Environmental Exposure, 300, 461, 497 Environmental Health, 120, 150, 300, 388, 390, 461 Enzymatic, 19, 39, 433, 443, 444, 450, 455, 461, 488, 507, 517 Enzyme Inhibitors, 16, 461, 505 Enzyme-Linked Immunosorbent Assay, 360, 461 Eosinophil, 462, 471 Eosinophilia, 269, 462, 464 Epidemic, 462, 524 Epidemiological, 49, 60, 462 Epidermal, 143, 192, 247, 462, 488, 491 Epidermis, 429, 441, 456, 462, 487, 501, 513 Epigastric, 462, 500 Epinephrine, 431, 457, 462, 495, 496, 532 Epithelial, 31, 430, 455, 462, 469, 473, 483, 526 Epithelial Cells, 462, 473, 483 Epithelioid Cells, 462 Epithelium, 440, 461, 462, 467, 535 Epitope, 41, 43, 51, 74, 95, 101, 108, 154, 181, 213, 324, 330, 462 Epoprostenol, 180, 462, 476 Erythema, 14, 186, 213, 285, 462, 526, 533 Erythrocytes, 318, 319, 433, 434, 442, 462, 500, 515 Erythromycin, 448, 462 Esophagitis, 362, 462 Esophagus, 362, 456, 462, 463, 472, 503, 515, 525 Essential Tremor, 394, 463 Estradiol, 45, 130, 463, 521 Estrogen, 12, 13, 24, 25, 44, 50, 84, 101, 198, 304, 313, 377, 463, 509 Estrogen receptor, 44, 50, 84, 101, 463 Estrogen Replacement Therapy, 313, 377, 463
544 Lupus
Ethnic Groups, 13, 47, 158, 237, 407, 446, 463 Eukaryotic Cells, 463, 478, 496, 498 Evacuation, 452, 463, 483 Evoke, 463, 525 Evoked Potentials, 268, 463 Excipients, 463, 506 Excitability, 463, 513 Excitation, 463, 466, 495 Excitatory, 463, 469 Excrete, 311, 436, 463, 482, 516 Exfoliation, 463, 494 Exhaustion, 463, 487 Exocrine, 463, 500 Exogenous, 50, 67, 72, 88, 99, 318, 333, 441, 444, 458, 460, 463, 468, 531 Exon, 120, 463 Extensor, 464, 512, 534 External-beam radiation, 464, 481, 513, 535 Extracellular, 22, 39, 158, 321, 345, 433, 451, 464, 465, 488, 491, 522 Extracellular Matrix, 321, 451, 464, 465, 488 Extracellular Matrix Proteins, 464, 488 Extracellular Space, 464 Extracorporeal, 157, 464 Extrarenal, 156, 186, 464 Extravascular, 65, 157, 464 Extremity, 13, 464, 500 Exudate, 67, 447, 464, 506 F Facial, 196, 299, 319, 325, 343, 464, 487, 500 Fallopian tube, 464, 516, 531 Family Health, 96, 464 Family Planning, 137, 389, 464 Family Practice, 100, 231, 464 Farnesyl, 341, 464 Fasciitis, 143, 163, 464 Fat, 430, 437, 440, 442, 444, 453, 459, 465, 484, 492, 507, 517, 522, 526 Fatigue, 11, 82, 160, 273, 311, 313, 350, 351, 360, 377, 405, 407, 413, 414, 424, 465, 472 Fatty acids, 85, 212, 264, 274, 276, 431, 457, 459, 465, 470, 485, 510 Febrile, 465, 486, 487 Feces, 452, 465, 525 Femoral, 20, 131, 379, 465, 507 Femoral Artery, 465 Femoral Vein, 20, 465, 507 Femur, 465 Fermentation, 465, 518
Ferritin, 218, 465 Fertilization in Vitro, 465, 508 Fetal Death, 10, 21, 465 Fetal Growth Retardation, 333, 465 Fetal Heart, 371, 465 Fetus, 104, 194, 294, 377, 429, 465, 476, 504, 508, 524, 533 Fibrin, 20, 441, 449, 465, 501, 503, 505, 506, 528 Fibrinogen, 20, 465, 500, 505, 511, 528 Fibroblasts, 39, 82, 451, 464, 465, 480 Fibrosarcoma, 465 Fibrosis, 6, 16, 83, 93, 104, 211, 394, 432, 452, 465, 519 Filgrastim, 303, 465 Filtration, 269, 273, 299, 466, 482 Fish Oils, 457, 466 Flow Cytometry, 26, 29, 36, 78, 103, 112, 113, 226, 327, 466 Fludarabine, 5, 306, 466 Fluorescence, 29, 79, 466 Fluorescent Dyes, 466 Fold, 43, 109, 466, 489 Forearm, 441, 465, 466 Fossa, 218, 446, 466 Free Radicals, 85, 436, 457, 466 Fungi, 435, 438, 466, 490, 529, 535 Fungus, 443, 466 G Gadolinium, 298, 466 Gait, 339, 467 Gallbladder, 362, 429, 440, 456, 467 Gallstones, 440, 467, 473 Gamma-Endorphin, 467 Ganglia, 429, 440, 467, 494, 502, 523 Ganglion, 467, 498, 535 Gangrene, 269, 429, 467 Gas, 239, 433, 444, 447, 467, 475, 478, 493, 495, 514, 526 Gastric, 143, 467, 472, 501 Gastric Juices, 467, 501 Gastric Mucosa, 467, 502 Gastrin, 467, 474 Gastroenteritis, 467, 518 Gastrointestinal tract, 328, 353, 467, 484, 521, 524 Gelatin, 467, 470, 526, 528 Gene Deletion, 16, 70, 467 Gene Dosage, 34, 467 Gene Expression, 31, 32, 37, 54, 70, 80, 90, 92, 106, 110, 113, 121, 179, 180, 271, 395, 468
Index 545
Gene Rearrangement, 95, 468 Gene Targeting, 88, 468 Gene Therapy, 34, 54, 175, 468 Genetic Code, 468, 496 Genetic Engineering, 441, 449, 468 Genetic Markers, 50, 58, 468 Genetic testing, 302, 318, 468, 507 Genital, 468, 533 Genitourinary, 468, 533 Genomics, 41, 46, 165, 468 Genotype, 57, 58, 155, 241, 468, 503 Germinal Center, 22, 38, 42, 177, 468 Gestation, 104, 294, 468, 502, 504, 524 Gestational, 104, 465, 468 Gestational Age, 104, 468 Giant Cells, 462, 468, 519 Gland, 336, 339, 378, 431, 447, 453, 469, 486, 500, 504, 510, 519, 520, 525, 529 Glomerular, 21, 25, 31, 47, 67, 88, 92, 95, 103, 115, 166, 246, 269, 363, 469, 481, 482, 516 Glomerular Filtration Rate, 269, 469, 482 Glomeruli, 31, 47, 88, 92, 99, 299, 319, 469 Glomerulonephritis, Membranous, 295, 469 Glomerulus, 67, 70, 96, 469, 494 Glucocorticoid, 346, 456, 469, 508 Glucose, 174, 390, 394, 446, 456, 469, 472, 479, 519, 523 Glucose Intolerance, 456, 469 Glucuronic Acid, 469, 473 Glutamate, 469 Glutamic Acid, 316, 469, 495, 509 Glutathione Peroxidase, 469, 520 Glycerol, 444, 469, 470, 503 Glycerophospholipids, 470, 503 Glycine, 325, 326, 390, 433, 440, 470, 495, 520 Glycoprotein, 129, 154, 174, 175, 240, 432, 465, 468, 470, 483, 521, 528, 531 Glycosaminoglycans, 261, 464, 470 Glycosidic, 470, 497 Glycosylation, 121, 470 Gonadal, 167, 470, 524 Gonadotropin, 245, 470 Governing Board, 470, 508 Gp120, 43, 74, 470, 502 Graft, 9, 122, 303, 470, 474, 477, 493 Graft Rejection, 470, 477 Graft Survival, 9, 470 Grafting, 138, 452, 470, 478 Graft-versus-host disease, 122, 470, 493
Gram-negative, 434, 461, 470, 493, 518 Gram-Negative Bacteria, 434, 461, 470 Granulocyte, 126, 149, 167, 198, 466, 470, 480 Granulocyte-Macrophage ColonyStimulating Factor, 149, 470 Granuloma, 196, 471 Gravis, 61, 239, 471 Growth factors, 31, 39, 471 Guanine, 141, 471, 513 Guanylate Cyclase, 471, 495 Guinea Pigs, 316, 471 H Haematological, 218, 471 Haematology, 143, 156, 189, 214, 240, 259, 322, 471 Hair follicles, 456, 471, 534 Half-Life, 471, 476 Halitosis, 375, 471 Haploid, 471, 504 Haplotypes, 115, 165, 250, 471 Haptens, 316, 431, 471, 514 Headache, 471, 479 Health Education, 409, 410, 471 Health Promotion, 363, 401, 471 Health Services, 36, 82, 472 Health Status, 97, 220, 290, 464, 472 Heart attack, 324, 444, 472 Heart failure, 472, 497 Heartbeat, 472, 526 Heartburn, 285, 362, 472, 473, 478 Hematology, 100, 145, 159, 189, 220, 237, 258, 354, 472 Hematopoietic growth factors, 374, 472 Hematopoietic Stem Cells, 87, 472 Hematuria, 5, 120, 472 Heme, 440, 454, 472 Hemiparesis, 472 Hemiplegia, 273, 472 Hemodialysis, 472, 482 Hemoglobin, 434, 462, 472, 483 Hemoglobinopathies, 468, 472 Hemoglobinuria, 394, 472 Hemolytic, 87, 111, 115, 119, 155, 303, 319, 325, 333, 343, 393, 464, 472 Hemorrhage, 145, 181, 235, 244, 250, 362, 459, 471, 472, 513, 525 Hemostasis, 198, 473, 521 Heparin, 14, 258, 266, 473, 501 Hepatic, 13, 157, 362, 431, 473 Hepatitis, 8, 123, 131, 362, 374, 473, 478 Hepatocytes, 473
546 Lupus
Hepatomegaly, 473, 478 Hereditary, 13, 29, 402, 432, 451, 473, 517 Heredity, 352, 408, 467, 468, 473 Herpetiformis, 136, 473 Heterogeneity, 33, 51, 53, 64, 81, 89, 92, 327, 431, 473 Hiatal Hernia, 362, 473 Hiccup, 447, 473 High blood cholesterol, 299, 473 Hippocampus, 64, 455, 473, 525 Histiocytic Necrotizing Lymphadenitis, 183, 473 Histiocytosis, 185, 202, 474 Histocompatibility, 89, 122, 161, 474 Histology, 16, 35, 474 Histone Deacetylase, 64, 474 Homeostasis, 50, 87, 109, 474 Homicide, 364, 474 Homodimer, 474, 530 Homogeneous, 316, 437, 474 Homologous, 27, 28, 52, 53, 76, 102, 325, 432, 453, 468, 474, 492, 520, 526 Hormonal, 13, 50, 112, 130, 171, 195, 238, 259, 439, 453, 463, 474 Hormone Replacement Therapy, 44, 297, 313, 403, 474 Horseradish Peroxidase, 461, 474 Housekeeping, 39, 474 Human Genome Project, 93, 395, 474 Humoral, 7, 61, 69, 73, 75, 88, 90, 94, 291, 336, 339, 340, 345, 470, 474, 477, 528 Humour, 474 Hybrid, 39, 59, 84, 111, 449, 474 Hybridization, 46, 474, 496 Hybridoma, 79, 113, 290, 326, 474 Hydralazine, 14, 106, 326, 333, 343, 360, 374, 409, 475 Hydrogen Peroxide, 71, 445, 469, 475, 484 Hydrolysis, 438, 441, 475, 503, 511, 531 Hydrophobic, 71, 470, 475, 484 Hydroxylation, 27, 443, 475 Hydroxylysine, 449, 475 Hydroxyproline, 433, 449, 475 Hyperbaric, 272, 475 Hyperbaric oxygen, 272, 475 Hyperbilirubinemia, 475, 482 Hypercalcemia, 448, 475 Hypercholesterolemia, 285, 458, 475 Hyperlipidemia, 6, 7, 458, 475 Hyperplasia, 45, 475 Hypersensitivity, 113, 303, 462, 475, 484, 517
Hypertension, 5, 6, 16, 175, 258, 343, 364, 406, 437, 444, 475, 481, 508 Hypertriglyceridemia, 458, 475 Hypertrophy, 475 Hypesthesia, 475, 494 Hypnotic, 439, 475, 528 Hypogammaglobulinemia, 450, 475 Hypokinesia, 476, 500 Hypothalamus, 71, 456, 476, 504, 509, 528 I Id, 56, 262, 284, 398, 409, 411, 420, 422, 476 Idiopathic, 63, 73, 75, 80, 106, 121, 148, 154, 166, 174, 237, 261, 299, 333, 374, 476, 519 Idiotype, 117, 256, 272, 316, 317, 476 Ileitis, 202, 476 Ileum, 476 Iliac Vein, 465, 476 Iloprost, 260, 280, 476 Immune Complex Diseases, 435, 476, 505 Immune function, 25, 71, 81, 92, 476, 477, 530 Immune Sera, 476 Immune Tolerance, 26, 56, 91, 316, 341, 476 Immunity, 42, 43, 69, 75, 91, 109, 165, 215, 254, 297, 346, 476, 477, 480, 529, 530 Immunization, 18, 43, 45, 51, 53, 57, 77, 91, 94, 233, 258, 320, 342, 383, 430, 476, 477 Immunoassay, 321, 339, 435, 461, 477 Immunodeficiency, 117, 172, 393, 450, 475, 477 Immunodeficiency syndrome, 450, 477 Immunodiffusion, 431, 477 Immunoelectrophoresis, 266, 431, 477 Immunofluorescence, 18, 45, 327, 363, 477, 491 Immunogenetics, 79, 85, 99, 122, 161, 170, 477 Immunogenic, 21, 325, 326, 328, 330, 344, 477, 484, 514 Immunoglobulin, 10, 25, 28, 33, 69, 72, 83, 87, 89, 91, 95, 109, 235, 317, 327, 332, 345, 390, 425, 435, 450, 477, 491 Immunohistochemistry, 26, 477 Immunologic Diseases, 66, 312, 318, 476, 477 Immunologic Factors, 4, 477 Immunophilin, 443, 477 Immunosuppressant, 432, 477, 489, 522 Immunosuppressive Agents, 5, 31, 200, 258, 325, 335, 407, 477
Index 547
Immunosuppressive therapy, 6, 38, 121, 130, 140, 176, 225, 243, 477 Immunotherapy, 26, 42, 74, 102, 323, 431, 441, 477 Impairment, 34, 38, 82, 94, 125, 136, 298, 325, 344, 362, 379, 438, 477, 489, 508, 512, 533 Implant radiation, 478, 481, 513, 535 Implantation, 451, 478 In situ, 36, 166, 478 In Situ Hybridization, 36, 478 In vivo, 16, 21, 23, 24, 25, 28, 29, 32, 36, 39, 47, 49, 52, 55, 67, 68, 70, 72, 75, 76, 77, 78, 79, 83, 89, 94, 95, 98, 102, 108, 116, 330, 334, 336, 338, 468, 473, 478, 499, 527, 528 Incision, 478, 481 Incontinence, 7, 478, 493, 525 Incubated, 29, 478 Incubation, 125, 322, 478 Indicative, 354, 478, 501, 533 Indigestion, 285, 362, 478 Indolent, 30, 478 Infancy, 110, 478 Infant Mortality, 364, 478 Infarction, 223, 362, 478, 506, 516 Infectious Mononucleosis, 326, 478 Infertility, 306, 478 Infestation, 479, 487 Infiltration, 469, 474, 479, 509, 535 Inflammatory bowel disease, 27, 346, 362, 479 Influenza, 233, 374, 479 Infusion, 279, 295, 306, 308, 479 Ingestion, 279, 471, 479, 506 Inhalation, 473, 479, 506, 522 Initiation, 40, 41, 70, 90, 91, 103, 110, 123, 479, 530 Initiator, 479, 480 Innervation, 479, 497 Inorganic, 479, 492 Inositol, 73, 479 Insecticides, 479, 503 Insight, 25, 32, 46, 53, 57, 59, 61, 65, 83, 479 Insulator, 479, 492 Insulin, 174, 245, 479 Insulin-dependent diabetes mellitus, 479 Intensive Care, 163, 237, 479 Interferon-alpha, 157, 180, 217, 291, 372, 480 Interleukin-1, 71, 90, 118, 152, 156, 177, 180, 219, 302, 480
Interleukin-10, 118, 180, 480 Interleukin-12, 156, 219, 480 Interleukin-15, 90, 219, 480 Interleukin-18, 152, 177, 219, 480 Interleukin-2, 146, 222, 256, 480 Interleukin-4, 147, 215, 480 Interleukin-6, 174, 295, 345, 480 Interleukins, 184, 477, 480 Intermittent, 102, 180, 260, 306, 458, 480, 502 Internal radiation, 480, 481, 513, 535 Interphase, 481, 496 Interstitial, 6, 105, 193, 199, 221, 442, 464, 481, 494, 516, 535 Intestinal, 67, 181, 274, 443, 444, 461, 481, 487 Intestine, 440, 442, 481, 483 Intoxication, 481, 535 Intracellular, 52, 90, 91, 147, 257, 274, 339, 340, 478, 481, 488, 495, 507, 510, 514, 520, 521 Intracranial Hypertension, 174, 471, 481, 500, 529 Intracranial Pressure, 481, 511 Intramuscular, 234, 481, 500 Intravascular, 232, 331, 481 Intravenous, 15, 89, 176, 181, 216, 229, 235, 273, 307, 323, 377, 390, 479, 481, 500 Intrinsic, 23, 48, 52, 338, 431, 440, 481, 500 Introns, 19, 481 Inulin, 469, 481 Invasive, 10, 53, 182, 207, 208, 217, 233, 311, 476, 481, 487 Involuntary, 440, 463, 481, 493, 522 Ionizing, 432, 461, 481, 513, 514 Ionomycin, 30, 481 Ions, 429, 440, 443, 457, 459, 475, 481, 511 Irradiation, 279, 296, 297, 303, 481, 535 Irritants, 375, 481 Ischemia, 78, 201, 269, 439, 482, 493, 516 Isoenzyme, 39, 453, 482 Isoniazid, 14, 151, 482 J Jaundice, 362, 475, 482 Joint Capsule, 379, 482, 526 K Kb, 56, 388, 482 Keloid, 335, 448, 482 Keratectomy, 186, 482 Keratoconjunctivitis, 300, 415, 482, 521 Keratoconjunctivitis Sicca, 300, 415, 482, 521
548 Lupus
Keratolytic, 455, 482 Kidney Failure, 303, 319, 390, 461, 482 Kidney Failure, Acute, 482 Kidney Failure, Chronic, 482 Kidney Glomerulus, 361, 483 Kidney Pelvis, 483, 532 Kinetic, 19, 481, 483 L Labile, 450, 483 Laboratory Personnel, 37, 483 Lacrimal, 412, 415, 482, 483, 521 Lactation, 483, 509 Lag, 97, 109, 483 Laminin, 94, 329, 440, 464, 483 Large Intestine, 456, 481, 483, 515, 522 Latency, 31, 483 Latent, 31, 483, 504, 508 Laxative, 431, 483, 523 Lectin, 57, 109, 194, 483, 488 Leflunomide, 129, 483 Leishmaniasis, 249, 483 Lens, 445, 483, 534 Lethal, 104, 483, 493 Leucine, 75, 483, 501 Leucocyte, 335, 462, 483, 486 Leukapheresis, 437, 483 Leukemia, 71, 185, 200, 207, 278, 393, 448, 468, 483 Leukocytes, 41, 140, 440, 442, 446, 480, 483, 484, 500, 531 Leukoencephalopathy, 227, 484 Leukopenia, 8, 319, 343, 376, 484 Leukotrienes, 174, 268, 276, 437, 459, 484 Libido, 434, 484 Library Services, 420, 484 Ligament, 339, 464, 484, 510 Ligands, 56, 68, 74, 78, 79, 212, 239, 345, 445, 484 Ligation, 68, 484 Linkage Disequilibrium, 33, 60, 63, 64, 69, 81, 484 Lipid, 21, 68, 150, 155, 272, 437, 438, 469, 479, 484, 492, 499 Lipid A, 150, 272, 484 Lipid Peroxidation, 21, 484, 499 Lipophilic, 72, 484 Lipopolysaccharide, 67, 470, 484 Lipoprotein, 127, 139, 152, 230, 458, 470, 473, 484, 485 Lipoprotein Lipase, 127, 484 Lipoprotein(a), 230, 484 Liposomes, 78, 485
Lipoxygenase, 184, 437, 484, 485 Liver scan, 485, 519 Localization, 16, 35, 56, 105, 291, 320, 341, 477, 485 Localized, 12, 14, 54, 320, 342, 362, 455, 472, 478, 483, 485, 493, 497, 504, 519, 532, 533 Locomotion, 485, 504 Lod, 63, 111, 485 Longitudinal study, 40, 154, 205, 485 Loop, 158, 485 Low-density lipoprotein, 18, 458, 484, 485 Lucida, 483, 485 Lumbar, 44, 298, 485, 523 Lumbar puncture, 298, 485, 523 Lumen, 39, 461, 485 Lupus Erythematosus, Systemic, 293, 298, 300, 305, 307, 309, 351, 393, 435, 486 Lutein Cells, 486, 509 Lymph node, 45, 46, 112, 311, 446, 473, 486, 518, 519 Lymphadenitis, 169, 257, 486 Lymphadenopathy, 126, 339, 478, 486 Lymphatic, 325, 353, 403, 461, 478, 486, 489, 497, 518, 523, 529 Lymphatic system, 353, 486, 518, 523, 529 Lymphoblastic, 486 Lymphoblasts, 430, 486 Lymphocyte, 25, 31, 47, 49, 55, 81, 89, 91, 98, 105, 113, 128, 141, 158, 159, 170, 178, 212, 214, 243, 258, 311, 370, 371, 435, 480, 486, 487, 488 Lymphocyte Subsets, 170, 486 Lymphocytic, 119, 193, 486 Lymphoid, 5, 26, 34, 48, 71, 85, 105, 303, 311, 435, 468, 474, 483, 486, 529 Lymphokine, 91, 486 Lymphoma, 89, 149, 154, 185, 200, 207, 208, 278, 280, 283, 331, 393, 486 Lymphopenia, 42, 178, 486 Lymphoproliferative, 448, 486 Lysine, 316, 475, 486, 531 Lytic, 486, 520 M Macrophage, 30, 66, 70, 77, 83, 471, 480, 486, 487 Macrophage Activation, 84, 487 Magnetic Resonance Imaging, 131, 183, 269, 301, 487, 519 Maintenance therapy, 198, 308, 487 Major Histocompatibility Complex, 59, 115, 117, 302, 332, 345, 471, 480, 487
Index 549
Malabsorption, 362, 394, 487 Malar, 11, 14, 152, 487 Malaria, 326, 487 Malaria, Falciparum, 487 Malaria, Vivax, 487 Malignancy, 66, 99, 193, 246, 487 Malignant, 280, 393, 436, 437, 465, 474, 487, 494, 509, 514, 519 Malnutrition, 431, 439, 487, 492 Mammary, 452, 484, 487 Mammogram, 306, 443, 487, 490 Mange, 487 Manic, 436, 487, 512 Manic-depressive psychosis, 487, 512 Manifest, 104, 132, 335, 472, 488 Marital Status, 58, 488 Matrix metalloproteinase, 213, 488 Medial, 438, 488, 498 Mediate, 17, 28, 30, 56, 71, 77, 79, 239, 445, 457, 488 Mediator, 30, 70, 88, 324, 480, 488, 521 Medical Records, 58, 300, 488, 517 Medicine, Kampo, 272, 488 MEDLINE, 389, 392, 394, 488 Megakaryocytes, 442, 488, 528 Melanin, 456, 488, 503, 532 Melanocytes, 488 Melanoma, 393, 488, 532 Membrane Lipids, 488, 503 Membrane Proteins, 485, 488 Memory, 26, 31, 38, 80, 85, 103, 298, 455, 468, 488 Menarche, 50, 488 Meninges, 446, 458, 489, 523 Meningitis, 139, 489 Menopause, 44, 50, 377, 489, 507, 508 Menstrual Cycle, 44, 489, 509 Menstruation, 432, 455, 489 Mental Disorders, 314, 476, 489, 512 Mental Health, iv, 15, 312, 314, 388, 391, 489 Mental Processes, 457, 489, 512 Mental Retardation, 395, 406, 489 Mercury, 466, 489 Mesenchymal, 438, 470, 489 Mesenteric, 269, 362, 489, 507 Mesentery, 489, 503, 524 Meta-Analysis, 36, 60, 229, 232, 489 Metabolite, 50, 142, 335, 441, 442, 489, 509 Metastasis, 445, 488, 489 Metastatic, 196, 227, 489 Methotrexate, 158, 196, 230, 260, 346, 489
Methoxychlor, 24, 489 Methyldopa, 14, 490 Methylprednisolone, 6, 136, 181, 196, 216, 273, 278, 279, 490 Methyltransferase, 76, 105, 106, 490 Mice Minute Virus, 490, 501 Microbe, 490, 530 Microbiology, 22, 25, 27, 31, 40, 56, 75, 95, 103, 107, 247, 430, 439, 490 Microcalcifications, 443, 490 Microorganism, 449, 490, 501, 534 Micro-organism, 455, 490, 504 Microscopy, 35, 318, 363, 440, 474, 490, 496 Microsomal, 8, 490 Microspheres, 327, 490 Microwaves, 490, 514 Migration, 47, 487, 490 Mineralocorticoids, 431, 453, 490 Minocycline, 197, 231, 374, 490 Miscarriage, 51, 490 Mitogen-Activated Protein Kinase Kinases, 490, 491 Mitogen-Activated Protein Kinases, 141, 491 Mitosis, 437, 491 Mixed Connective Tissue Disease, 202, 279, 403, 408, 491 Mobility, 45, 169, 491 Mobilization, 303, 491 Modeling, 36, 62, 458, 491 Modification, 42, 72, 80, 91, 92, 433, 468, 491, 513 Modulator, 125, 491 Molecular mass, 327, 491 Monitor, 35, 45, 51, 66, 89, 172, 307, 322, 453, 491, 496, 501 Monoclonal antibodies, 77, 78, 221, 234, 326, 328, 491, 518 Monocyte, 55, 66, 77, 123, 198, 199, 239, 492 Monokines, 219, 492 Mononuclear, 40, 47, 156, 175, 226, 340, 464, 471, 478, 492, 531 Monophosphate, 125, 492 Morphogenesis, 111, 492 Morphology, 328, 471, 472, 487, 492 Motility, 492, 521 Motion Sickness, 492, 493 Mucins, 492, 518 Mucocutaneous, 4, 47, 483, 492 Mucosa, 319, 362, 363, 467, 486, 492, 509, 525
550 Lupus
Mucus, 412, 492, 532 Multiparous, 218, 492 Multiple sclerosis, 41, 112, 176, 219, 318, 492, 498 Multivalent, 439, 492 Muscle Fibers, 492, 493 Muscle relaxant, 435, 492, 503 Muscle Spindles, 492, 503 Muscular Atrophy, 394, 492 Muscular Dystrophies, 458, 492 Musculoskeletal System, 353, 493 Mustard Gas, 482, 493 Mutagenic, 333, 432, 493 Myalgia, 279, 479, 493 Myasthenia, 61, 239, 493 Mycophenolate mofetil, 6, 7, 15, 195, 200, 201, 235, 244, 245, 257, 258, 259, 493 Mycoplasma, 163, 319, 493 Myelin, 41, 492, 493, 507, 520 Myelitis, 150, 201, 493, 495 Myelogenous, 493 Myeloma, 189, 200, 474, 493 Myocardial infarction, 21, 78, 247, 331, 453, 490, 493 Myocarditis, 66, 104, 157, 201, 493 Myocardium, 104, 490, 493 Myopathy, 374, 493 Myosin, 443, 493 Myositis, 177, 300, 374, 398, 408, 493 Myotonic Dystrophy, 394, 493 N Naive, 26, 38, 42, 88, 116, 493 Nasal Mucosa, 479, 493 Natural killer cells, 480, 493 Nausea, 362, 375, 435, 436, 467, 478, 493, 511, 532 NCI, 1, 305, 314, 387, 448, 494 Necrolysis, 192, 494 Neonatal, 13, 14, 24, 30, 84, 96, 99, 104, 133, 164, 169, 177, 188, 194, 202, 203, 214, 246, 259, 293, 294, 379, 403, 406, 478, 494 Neoplasia, 393, 494 Neoplasm, 494, 519, 531 Neoplastic, 486, 494 Neopterin, 140, 270, 494 Nephron, 193, 223, 266, 279, 469, 494 Nephropathy, 6, 8, 123, 158, 166, 193, 195, 250, 295, 299, 303, 482, 494 Nephrosis, 494 Nephrotic, 5, 6, 27, 294, 295, 303, 380, 469, 494
Nephrotic Syndrome, 5, 6, 27, 294, 295, 303, 380, 469, 494 Nephrotoxic, 56, 494 Networks, 216, 292, 494 Neural, 216, 431, 433, 474, 494 Neuritis, 209, 494, 495, 498 Neuroendocrine, 71, 494 Neurologic, 66, 82, 351, 380, 390, 435, 495 Neurology, 100, 166, 170, 178, 191, 205, 213, 238, 241, 259, 269, 276, 277, 278, 279, 495 Neuromuscular, 429, 495, 497 Neuromuscular Junction, 429, 495, 497 Neuromyelitis Optica, 256, 495 Neuropathy, 210, 213, 495 Neuropsychological Tests, 82, 495 Neuropsychology, 79, 166, 495 Neuroretinitis, 495, 517 Neurosecretory Systems, 460, 495 Neurosyphilis, 495, 500 Neurotransmitter, 429, 430, 433, 438, 442, 457, 469, 470, 495, 496, 521, 525 Neutrons, 432, 481, 495, 513 Neutrophil, 55, 216, 260, 432, 495 Nitric Oxide, 70, 99, 152, 241, 257, 495 Nitrogen, 431, 432, 434, 454, 464, 482, 491, 495, 531 Nonverbal Communication, 495, 512 Norepinephrine, 431, 457, 490, 495, 496 Nuclear Envelope, 39, 496 Nuclear Pore, 496 Nuclear Proteins, 26, 34, 496 Nuclei, 320, 342, 432, 468, 481, 487, 491, 495, 496, 498, 511, 518 Nucleic acid, 42, 317, 318, 320, 340, 341, 444, 454, 468, 474, 478, 495, 496, 513, 518, 534 Nucleic Acid Hybridization, 474, 496 Nucleic Acid Probes, 340, 496 Nucleocapsid, 496, 534 Nucleolus, 327, 496, 518 Nucleolus Organizer Region, 327, 496 Nucleoprotein, 23, 146, 496 Nucleosomes, 22, 40, 73, 91, 95, 99, 243, 320, 329, 342, 496 Nutritional Status, 353, 497 O Observational study, 104, 129, 497 Obstetrics, 100, 168, 255, 497 Ocular, 146, 223, 497 Oedema, 213, 277, 497 Ointments, 375, 497
Index 551
Oligosaccharides, 109, 497 Oliguria, 482, 497 Oncogene, 212, 339, 393, 497 Onychomycosis, 219, 497 Oophorectomy, 49, 497 Opacity, 445, 455, 497 Operon, 497, 516 Ophthalmic, 375, 497 Ophthalmologic, 352, 497 Ophthalmology, 134, 147, 178, 204, 210, 231, 497 Ophthalmoplegia, 181, 497 Opioid Peptides, 497 Opsin, 498, 517, 518 Optic Chiasm, 476, 495, 498 Optic disc, 498 Optic Nerve, 495, 498, 499, 512, 516, 517, 519 Optic Nerve Diseases, 498, 512 Optic Neuritis, 129, 498 Oral Health, 8, 498 Oral Hygiene, 471, 498 Oral Manifestations, 8, 498 Orbital, 498 Organelles, 446, 454, 488, 498 Osmotic, 431, 498, 521 Osteoarthritis, 36, 113, 311, 358, 498 Osteonecrosis, 210, 211, 379, 499 Osteoporosis, 27, 44, 210, 258, 324, 353, 377, 379, 400, 463, 499 Outpatient, 499 Ovariectomy, 84, 499 Ovaries, 497, 499, 516, 521, 531 Ovary, 463, 499, 525 Overexpress, 76, 106, 499 Ovulation, 176, 499 Ovulation Induction, 176, 499 Ovum, 455, 468, 499, 509, 535 Oxidants, 212, 276, 499 Oxidation, 19, 21, 72, 429, 436, 437, 441, 454, 469, 484, 499 Oxidation-Reduction, 441, 499 Oxidative Stress, 85, 126, 132, 499 Oxygenation, 157, 499 P Pachymeningitis, 489, 499 Palliative, 499, 528 Palsy, 209, 499 Pancreas, 362, 429, 456, 479, 500, 524, 531 Pancreatic, 53, 285, 393, 500 Pancreatic cancer, 393, 500 Pancytopenia, 202, 235, 500
Panniculitis, 14, 500 Papilledema, 500, 511 Paradoxical, 19, 47, 500 Paralysis, 472, 497, 500 Paraparesis, 500 Parasite, 257, 319, 500 Parathyroid, 443, 500 Parathyroid hormone, 443, 500 Parenteral, 322, 323, 500 Paresis, 161, 472, 494, 500 Paresthesias, 494, 500 Parkinsonism, 183, 227, 257, 436, 500 Parotid, 212, 500, 519 Paroxysmal, 394, 500 Partial remission, 8, 500, 515 Partial response, 500 Partial Thromboplastin Time, 129, 185, 332, 338, 500 Parturition, 497, 501, 509 Parvovirus, 172, 490, 501 Pathogen, 478, 501 Pathologic, 8, 64, 92, 106, 182, 328, 333, 429, 437, 441, 443, 452, 475, 501, 512, 516, 523, 533 Pathologic Processes, 437, 501 Pathologies, 344, 501 Pathophysiology, 54, 65, 501 Patient Advocacy, 501 Patient Care Team, 405, 406, 501 Patient Education, 8, 358, 402, 414, 418, 420, 426, 501 Pedigree, 55, 60, 64, 501 Pelvic, 460, 501, 510 Pelvis, 429, 485, 499, 501, 533 Pemphigus, 136, 213, 429, 501 Penis, 501, 516 Pepsin, 501 Pepsin A, 501 Peptic, 362, 501 Peptic Ulcer, 362, 501 Peptide Chain Elongation, 448, 502 Peptide T, 74, 77, 112, 502 Percutaneous, 131, 502 Perennial, 502, 531 Perfusion, 232, 267, 278, 279, 502 Pericardium, 104, 502, 527 Perinatal, 211, 478, 502 Periodontal disease, 8, 375, 502 Periodontitis, 229, 502 Peripheral Nervous System, 472, 490, 495, 499, 500, 502, 525
552 Lupus
Peripheral Nervous System Diseases, 472, 500, 502 Peripheral stem cells, 470, 502 Peritoneal, 28, 67, 156, 497, 502 Peritoneal Cavity, 497, 502 Peritoneal Dialysis, 156, 502 Peritoneum, 489, 502, 503, 517 Peritonitis, 134, 140, 156, 222, 503 Pesticides, 24, 479, 503 PH, 27, 121, 150, 232, 240, 248, 267, 269, 271, 279, 280, 503 Phagocyte, 499, 503 Phagocytosis, 23, 47, 198, 503 Pharmacokinetic, 503 Pharmacologic, 83, 99, 333, 434, 471, 503, 530 Pharynx, 479, 503 Phenylalanine, 501, 503, 531 Phenytoin, 234, 503 Phospholipases, 503, 521 Phospholipids, 21, 36, 156, 322, 337, 435, 436, 444, 465, 479, 484, 488, 503, 511 Phosphorus, 443, 503 Phosphorylated, 45, 491, 503 Phosphorylation, 26, 28, 73, 90, 107, 115, 121, 141, 491, 503, 511 Photoallergy, 504 Photocoagulation, 449, 504 Photosensitivity, 162, 214, 267, 285, 407, 504 Physical Therapy, 350, 504 Physiologic, 64, 431, 471, 476, 481, 489, 504, 510, 514, 516, 531 Physiology, 13, 362, 472, 494, 504 Pigments, 440, 444, 504, 517 Pilot Projects, 83, 504 Pilot study, 61, 204, 235, 261, 504 Pituitary Gland, 453, 504, 509 Placebos, 351, 504 Placenta, 104, 463, 504, 509, 512 Placental Insufficiency, 377, 504 Plague, 79, 504 Plant Oils, 497, 504 Plants, 97, 432, 438, 442, 444, 469, 481, 483, 492, 496, 504, 507, 519, 530, 531 Plaque, 35, 196, 504 Plasma cells, 138, 435, 493, 505 Plasma Exchange, 132, 173, 338, 505 Plasma protein, 431, 461, 505, 511, 521 Plasmapheresis, 7, 303, 350, 437, 505 Plasmin, 322, 505 Plasminogen, 505
Plasminogen Activators, 505 Platelet Activation, 505, 521 Platelet Aggregation, 434, 462, 476, 495, 505, 510, 528 Plateletpheresis, 437, 505 Platelets, 20, 111, 184, 218, 290, 495, 500, 505, 528 Platinum, 485, 505 Pleura, 505, 506 Pleural, 497, 505, 506 Pleural cavity, 497, 506 Pleurisy, 317, 506 Pneumoconiosis, 506, 522 Pneumonia, 57, 202, 214, 390, 452, 506 Pneumonitis, 105, 193, 506 Point Mutation, 107, 506 Poisoning, 443, 467, 481, 489, 494, 506, 518 Polyarteritis Nodosa, 55, 303, 354, 476, 506 Polyarthritis, 482, 506, 521 Polycystic, 394, 506 Polyethylene, 169, 316, 323, 506, 526 Polyethylene Glycols, 169, 506, 526 Polymerase, 19, 31, 45, 46, 215, 327, 506, 516 Polymerase Chain Reaction, 19, 31, 46, 506 Polymers, 332, 506, 507, 511 Polymorphic, 39, 50, 69, 215, 340, 456, 507 Polymorphism, 49, 51, 64, 65, 81, 108, 111, 120, 122, 159, 161, 171, 180, 185, 194, 229, 241, 242, 340, 507 Polyradiculoneuropathy, 238, 507 Polyradiculopathy, 215, 507 Polysaccharide, 431, 435, 446, 507, 511 Polyunsaturated fat, 174, 256, 272, 507, 528 Popliteal, 465, 507 Popliteal Vein, 465, 507 Portal Vein, 157, 507 Posterior, 150, 218, 433, 438, 446, 447, 457, 498, 500, 507, 519 Postmenopausal, 297, 313, 377, 463, 499, 507 Postnatal, 379, 507, 524 Postnatal Care, 379, 507 Postsynaptic, 507, 521 Post-translational, 42, 91, 434, 507, 521 Potassium, 174, 279, 490, 507, 513 Potentiates, 480, 507 Potentiation, 507, 521 Practicability, 508, 531 Practice Guidelines, 391, 409, 508 Prasterone, 151, 508
Index 553
Preclinical, 37, 103, 508 Predisposition, 4, 33, 49, 50, 58, 60, 85, 95, 110, 115, 318, 322, 333, 341, 407, 508 Prednisolone, 7, 15, 147, 198, 204, 277, 490, 508 Prednisone, 12, 61, 100, 104, 199, 244, 299, 303, 304, 306, 308, 310, 325, 365, 377, 508 Preeclampsia, 255, 377, 379, 508 Pregnancy Outcome, 307, 379, 508 Pregnancy Tests, 468, 508 Pregnenolone, 230, 288, 508 Premedication, 10, 508 Premenopausal, 35, 126, 216, 297, 377, 508 Prenatal, 379, 459, 508 Prenatal Care, 379, 508 Probe, 31, 79, 508 Probenecid, 318, 508 Problem Solving, 312, 509 Procainamide, 14, 105, 106, 326, 332, 333, 343, 374, 409, 509 Procaine, 509 Prodrug, 346, 509 Progesterone, 509, 524 Prognostic factor, 133, 509 Projection, 455, 496, 498, 509, 515 Prolactin, 99, 151, 219, 230, 509 Prolapse, 197, 509 Proliferating Cell Nuclear Antigen, 128, 509 Proline, 449, 475, 509 Promoter, 45, 47, 57, 65, 69, 73, 98, 122, 139, 146, 159, 194, 206, 241, 256, 509 Proneness, 338, 509 Pro-Opiomelanocortin, 467, 498, 509 Prophylaxis, 4, 151, 179, 390, 509, 533 Proportional, 324, 461, 509 Prospective study, 83, 145, 177, 179, 485, 510 Prostaglandin, 39, 218, 462, 510, 528 Prostaglandin Endoperoxides, 462, 510, 528 Prostaglandins A, 510 Prostate, 393, 510, 516 Prosthesis, 181, 510 Protease, 19, 43, 46, 74, 209, 335, 432, 449, 510 Protease Inhibitors, 335, 510 Protective Clothing, 377, 510 Protein C, 21, 22, 29, 226, 320, 333, 338, 342, 431, 433, 437, 439, 449, 465, 484, 496, 510 Protein Conformation, 433, 510
Protein Kinase C, 491, 511 Protein Kinases, 340, 491, 511 Protein S, 64, 85, 90, 102, 113, 360, 394, 395, 441, 448, 451, 462, 468, 510, 511, 518, 527 Protein-Serine-Threonine Kinases, 491, 511 Proteinuria, 5, 7, 8, 20, 29, 258, 299, 325, 469, 494, 508, 511 Proteoglycans, 440, 464, 511 Proteolytic, 35, 74, 432, 450, 461, 465, 505, 511 Prothrombin, 19, 51, 146, 184, 219, 221, 266, 332, 500, 511, 528 Prothrombin Time, 146, 332, 511 Protocol, 112, 214, 301, 310, 370, 390, 504, 511 Protons, 432, 475, 481, 511, 513 Protozoa, 483, 490, 511 Protozoan, 487, 511 Proximal, 12, 24, 94, 131, 219, 457, 511 Pruritic, 458, 511 Pseudotumor Cerebri, 223, 481, 511 Psoriasis, 47, 61, 113, 493, 512 Psychiatric, 63, 78, 82, 281, 298, 351, 489, 512 Psychiatry, 79, 132, 170, 205, 281, 512 Psychic, 484, 489, 512, 520 Psychoactive, 512, 535 Psychology, 17, 457, 495, 512 Psychophysiology, 495, 512 Psychosis, 244, 436, 468, 512 Psychotherapy, 162, 167, 512 Public Policy, 389, 512 Puerperium, 497, 512 Pulmonary Artery, 441, 512, 533 Pulmonary Edema, 447, 482, 512 Pulmonary hypertension, 180, 238, 260, 331, 462, 512 Pulse, 6, 9, 133, 136, 188, 196, 225, 278, 279, 335, 376, 377, 491, 512 Pupil, 452, 498, 512 Purifying, 28, 29, 512 Purines, 512, 520 Purpura, 209, 212, 231, 240, 303, 325, 513 Purulent, 429, 513, 533 Pustular, 473, 513 Putrefaction, 467, 513 Pyrimidines, 513, 520 Q Quackery, 350, 513
554 Lupus
Quality of Life, 17, 62, 83, 150, 272, 306, 309, 513 Quiescent, 513, 534 Quinidine, 332, 409, 513 Quinine, 513 R Race, 15, 44, 58, 145, 209, 490, 513 Radiation, 48, 461, 464, 466, 475, 476, 481, 513, 514, 519, 532, 535 Radiation Chimera, 48, 513 Radiation therapy, 464, 475, 481, 513, 535 Radio Waves, 298, 308, 490, 514 Radioactive, 311, 442, 471, 475, 478, 480, 481, 485, 492, 496, 513, 514, 519, 527, 532, 535 Radiography, 468, 514 Radioimmunoassay, 268, 514 Radiolabeled, 481, 513, 514, 535 Radiological, 502, 514 Radiotherapy, 442, 481, 513, 514, 535 Randomized, 17, 89, 104, 142, 143, 151, 176, 187, 225, 244, 259, 273, 297, 305, 310, 459, 514 Randomized Controlled Trials, 143, 514 Rarefaction, 438, 514 Reagent, 100, 266, 321, 447, 514 Reality Testing, 512, 514 Receptors, Antigen, 450, 514 Receptors, Serotonin, 514, 521 Recombinant, 19, 36, 37, 38, 43, 52, 53, 88, 96, 107, 111, 131, 146, 150, 374, 383, 514, 515, 533 Recombinant Proteins, 36, 39, 515 Recombination, 27, 76, 111, 157, 468, 515 Reconstitution, 5, 66, 96, 115, 222, 297, 303, 515 Rectal, 306, 515, 526 Rectum, 182, 436, 442, 449, 456, 467, 478, 479, 483, 510, 515, 521 Recur, 66, 406, 515 Red blood cells, 434, 462, 472, 515, 519 Red Nucleus, 438, 515 Reductase, 51, 489, 515 Refer, 1, 442, 450, 466, 485, 493, 495, 512, 515, 530 Reflux, 362, 515 Refraction, 515, 523 Refractory, 90, 168, 188, 196, 200, 258, 296, 297, 309, 459, 515 Regeneration, 515 Regimen, 7, 174, 297, 303, 306, 340, 370, 448, 459, 515
Regurgitation, 197, 472, 515 Relapse, 8, 10, 103, 143, 201, 211, 515 Relaxation Techniques, 353, 515 Reliability, 9, 82, 515 Remission, 11, 38, 40, 66, 128, 282, 283, 296, 323, 352, 403, 406, 487, 488, 515 Remission Induction, 38, 515 Renal capsule, 31, 515 Renal cell carcinoma, 223, 515 Renal failure, 6, 9, 98, 284, 325, 363, 404, 516 Renal tubular, 161, 508, 516 Renal tubular acidosis, 161, 516 Renin, 444, 516 Renin-Angiotensin System, 444, 516 Reperfusion, 56, 516 Reperfusion Injury, 516 Repressor, 76, 497, 516 Reproduction Techniques, 508, 516 Reproductive system, 350, 516 Research Design, 69, 85, 516 Resorption, 443, 516 Respiration, 178, 250, 444, 491, 516 Restoration, 504, 515, 516, 535 Retina, 190, 323, 406, 447, 451, 483, 495, 498, 516, 517, 518, 534 Retinal, 209, 260, 498, 516, 518 Retinitis, 231, 517 Retinoblastoma, 393, 517 Retinol, 516, 517, 518 Retinopathy, 192, 504, 517 Retrobulbar, 495, 498, 517 Retroperitoneal, 230, 431, 517 Retrospective, 3, 11, 62, 83, 142, 145, 176, 226, 234, 517 Retrospective Studies, 83, 517 Retrospective study, 145, 176, 517 Retroviral vector, 31, 87, 468, 517 Retrovirus, 69, 229, 517 Reverberant, 456, 517 Rhodopsin, 498, 517, 518 Ribonuclease, 491, 518 Ribonucleic acid, 329, 518 Ribonucleoproteins, 52, 91, 97, 104, 518 Ribose, 430, 454, 518 Ribosomal Proteins, 127, 324, 518 Ribosome, 518, 530 Rigidity, 481, 500, 504, 518 Risk patient, 391, 406, 518 Rituximab, 89, 241, 293, 518 Rod, 439, 518 Rodenticides, 503, 518
Index 555
Rubella, 231, 518 Ruminants, 434, 518 S Saliva, 375, 412, 518 Salivary, 84, 375, 415, 454, 456, 500, 518, 521, 535 Salivary glands, 84, 375, 454, 456, 518, 521 Salmonella, 228, 247, 467, 518 Salmonellosis, 235, 519 Saphenous, 452, 519 Saphenous Vein, 452, 519 Saponins, 519, 524 Sarcoidosis, 519 Sarcoma, 246, 465, 519 Scans, 33, 110, 143, 301, 519 Scatter, 519, 532 Schizoid, 519, 535 Schizophrenia, 519, 535 Schizotypal Personality Disorder, 519, 535 Sclera, 447, 451, 519 Scleroderma, 12, 61, 82, 125, 179, 225, 285, 300, 326, 355, 408, 415, 437, 464, 491, 519 Sclerosis, 12, 41, 181, 205, 296, 354, 355, 394, 437, 438, 492, 519 Sclerotic, 10, 519 Screening, 37, 51, 54, 101, 107, 132, 165, 210, 295, 306, 308, 327, 377, 378, 448, 501, 519, 532 Sebaceous, 456, 482, 519, 534 Sebaceous gland, 456, 482, 519, 534 Secretion, 29, 42, 431, 453, 474, 479, 480, 482, 483, 490, 492, 520, 521, 530 Secretory, 335, 336, 520 Sediment, 179, 520, 532 Sedimentation, 309, 446, 486, 520 Segregation, 50, 111, 439, 515, 520 Seizures, 6, 278, 299, 424, 500, 503, 520, 524 Selection Bias, 36, 520 Selenium, 264, 273, 520 Self Care, 404, 520 Semen, 510, 520 Semisynthetic, 448, 490, 520 Senile, 499, 520 Sensory loss, 493, 520, 527 Sepsis, 214, 319, 520 Sequence Homology, 502, 520 Sequencing, 19, 24, 37, 62, 107, 111, 113, 324, 507, 520 Serine, 19, 43, 74, 335, 340, 460, 490, 511, 520, 531 Serologic, 8, 18, 50, 66, 78, 120, 154, 186, 333, 477, 520, 526
Serology, 61, 520 Serositis, 111, 380, 520 Serotonin, 158, 436, 495, 514, 520, 531 Serous, 461, 505, 520, 521 Serum Albumin, 8, 441, 514, 521 Sex Characteristics, 430, 434, 521, 527 Sex Determination, 394, 521 Sex Hormone-Binding Globulin, 102, 521 Sexually Transmitted Diseases, 364, 521 Shock, 521, 531 Sicca, 125, 196, 248, 375, 521 Sigmoid, 182, 521 Sigmoid Colon, 182, 521 Sigmoidoscopy, 306, 521 Signal Transduction, 26, 45, 74, 107, 141, 339, 340, 443, 479, 521 Signs and Symptoms, 361, 404, 506, 515, 521 Silicosis, 181, 522 Sirolimus, 299, 522 Skeletal, 12, 350, 379, 434, 453, 492, 493, 513, 522 Skeleton, 429, 465, 482, 510, 522 Skin graft, 192, 522 Skin test, 299, 308, 522 Skull, 481, 522, 527 Small intestine, 448, 458, 474, 476, 481, 522, 531 Smooth muscle, 8, 70, 432, 434, 451, 510, 516, 522, 525 Sneezing, 522, 525 Social Environment, 513, 522 Social Security, 514, 522 Social Support, 17, 292, 312, 522, 525 Socioeconomic Factors, 15, 522 Sodium, 312, 462, 490, 513, 522 Soft tissue, 442, 464, 465, 497, 522 Soma, 522 Somatic, 43, 54, 79, 117, 118, 185, 430, 474, 491, 502, 522 Somatic mutations, 79, 185, 522 Sorbitol, 390, 523 Sound wave, 451, 523, 532 Soybean Oil, 507, 523 Specialist, 415, 523 Specificity, 19, 22, 36, 43, 51, 65, 72, 74, 82, 87, 88, 103, 190, 254, 338, 361, 431, 437, 460, 523 Spectroscopic, 166, 523 Spectrum, 16, 29, 46, 52, 73, 88, 177, 328, 372, 490, 514, 523 Sperm, 434, 447, 522, 523
556 Lupus
Sphincter, 523, 525 Spinal cord, 298, 442, 446, 447, 458, 460, 467, 472, 489, 493, 494, 495, 499, 500, 502, 523 Spinal Cord Diseases, 472, 500, 523 Spinal Cord Vascular Diseases, 493, 523 Spinal Nerve Roots, 507, 523 Spinal tap, 298, 485, 523 Spleen, 29, 46, 49, 67, 311, 454, 474, 486, 519, 523, 524 Splenectomy, 49, 105, 524 Splenic Vein, 507, 524 Splenomegaly, 62, 339, 478, 524 Spondylitis, 236, 311, 412, 524 Spontaneous Abortion, 331, 334, 508, 524 Sporadic, 101, 517, 524 Stabilization, 280, 503, 524 Stabilizer, 390, 524 Staging, 519, 524 Staphylococcus, 467, 490, 524 Stasis, 249, 524, 533 Status Epilepticus, 137, 524 Stem cell transplantation, 99, 168, 169, 303, 524 Stem Cells, 192, 502, 524 Stenosis, 197, 220, 231, 524, 525 Stent, 223, 524 Sterile, 500, 524, 531 Sterility, 454, 479, 524 Steroid, 61, 133, 134, 137, 142, 151, 259, 294, 304, 306, 371, 440, 453, 454, 473, 508, 519, 524 Steroid therapy, 134, 259, 524 Stillbirth, 508, 524 Stimulant, 31, 525 Stimulus, 30, 31, 35, 45, 66, 268, 452, 458, 459, 463, 479, 483, 500, 525, 528 Stool, 449, 478, 483, 525 Strand, 151, 187, 329, 506, 525 Stress management, 4, 350, 525 Stress urinary, 7, 525 Stria, 339, 525 Stria Vascularis, 339, 525 Stricture, 524, 525 Stroke, 21, 78, 189, 297, 314, 331, 364, 388, 410, 444, 525 Stroma, 110, 525 Stromal, 442, 460, 525 Stromal Cells, 442, 525 Subclinical, 19, 104, 478, 520, 525 Subcutaneous, 119, 230, 234, 446, 458, 497, 500, 525
Subiculum, 473, 525 Subspecies, 523, 525 Substance P, 442, 462, 489, 515, 520, 525 Substrate, 74, 90, 322, 461, 526 Subungual, 219, 526 Suction, 466, 526 Sudden death, 101, 526 Sunburn, 285, 526, 532 Superoxide, 99, 526 Supplementation, 85, 273, 276, 370, 526 Support group, 4, 281, 353, 365, 413, 414, 526 Suppository, 506, 526 Suppression, 16, 280, 375, 453, 526 Suppressive, 56, 319, 526 Symphysis, 447, 510, 526 Symptomatic, 31, 211, 435, 526 Synaptic, 495, 521, 526 Synergistic, 106, 509, 526 Synovial, 130, 234, 438, 482, 526 Synovial Cyst, 234, 526 Synovial Fluid, 130, 526 Synovial Membrane, 438, 482, 526 Syphilis, 444, 495, 526 Syphilis Serodiagnosis, 444, 526 Systemic disease, 162, 363, 406, 438, 526 Systemic therapy, 14, 447, 527 Systolic, 475, 527 T Tachycardia, 439, 527 Tachypnea, 439, 527 Tacrolimus, 152, 243, 248, 527 Tear Gases, 482, 527 Technetium, 121, 178, 232, 527 Telangiectasia, 394, 527 Telencephalon, 440, 446, 527 Temporal, 35, 87, 374, 473, 527 Tendon, 233, 467, 526, 527 Terminator, 449, 527 Testis, 434, 463, 527 Testosterone, 336, 515, 521, 527 Tetracycline, 490, 527 Thalamic, 438, 527 Thalamic Diseases, 438, 527 Thalidomide, 188, 239, 250, 305, 528 Therapeutics, 113, 382, 528 Thermal, 282, 457, 495, 506, 528 Thigh, 465, 528 Third Ventricle, 476, 528 Thoracic, 178, 207, 250, 456, 505, 528, 535 Thorax, 429, 485, 528 Threonine, 340, 490, 502, 511, 520, 528
Index 557
Threshold, 25, 48, 93, 112, 463, 475, 528 Thrombin, 19, 465, 505, 510, 511, 528 Thrombocytes, 505, 528 Thrombocytopenia, 13, 21, 110, 214, 242, 267, 322, 331, 332, 376, 528 Thromboembolism, 143, 528 Thrombomodulin, 152, 510, 528 Thrombopenia, 436, 528 Thromboplastin, 146, 338, 511, 528 Thrombopoietin, 231, 528 Thromboses, 338, 436, 528 Thromboxanes, 39, 437, 459, 510, 528 Thrombus, 19, 72, 453, 478, 505, 528, 533 Thrush, 443, 529 Thymus, 48, 242, 316, 448, 476, 486, 529 Thyroid, 54, 359, 360, 378, 500, 529, 532 Thyroid Gland, 378, 500, 529 Thyroid Hormones, 529, 532 Thyroiditis, 378, 529 Thyroxine, 431, 503, 529 Time Management, 525, 529 Tinnitus, 511, 529 Tissue Extracts, 322, 529 T-lymphocyte, 113, 177, 178, 325, 335, 435, 443, 448, 468, 480, 514, 527, 529 Tome, 288, 529 Tomography, 310, 451, 519, 529 Tonsils, 307, 529 Tooth Preparation, 430, 529 Topical, 12, 13, 14, 152, 243, 305, 335, 475, 529 Torsion, 478, 529 Toxaemia, 508, 529 Toxic, iv, 86, 89, 93, 94, 192, 301, 303, 432, 447, 454, 460, 461, 476, 494, 495, 520, 530 Toxicity, 5, 6, 8, 20, 86, 136, 155, 221, 296, 299, 306, 309, 458, 489, 530 Toxicokinetics, 530 Toxicology, 390, 530 Toxin, 334, 461, 529, 530 Trachea, 503, 529, 530 Transcriptase, 226, 517, 530 Transcription Factors, 44, 530 Transduction, 26, 87, 521, 530 Transfection, 73, 76, 441, 468, 530 Transfer Factor, 476, 530 Transferases, 470, 530 Transforming Growth Factor beta, 271, 530 Transgenes, 28, 69, 110, 530 Translation, 79, 83, 90, 327, 433, 462, 530 Translational, 91, 530
Translocation, 67, 76, 448, 462, 531 Transmitter, 429, 457, 488, 490, 496, 531 Trauma, 27, 131, 440, 462, 471, 527, 529, 531 Treatment Outcome, 340, 531 Trees, 36, 531 Tremor, 500, 531 Trypsin, 360, 432, 461, 531 Trypsin Inhibitors, 360, 531 Tryptophan, 449, 520, 531 Tubal ligation, 377, 531 Tubercle, 531 Tuberculin, 308, 531 Tuberculostatic, 482, 531 Tuberous Sclerosis, 394, 531 Tumor Necrosis Factor, 57, 108, 115, 152, 224, 302, 528, 531 Tumour, 225, 245, 467, 531 Tunica, 492, 531 Tyrosine, 26, 28, 73, 83, 102, 141, 340, 457, 531 U Ulcer, 446, 501, 532 Ulcerative colitis, 346, 479, 532 Ultrasonography, 468, 532 Ultrasound test, 294, 532 Ultraviolet radiation, 353, 526, 532 Unconscious, 455, 476, 532 Uranium, 527, 532 Uremia, 482, 516, 532 Ureter, 362, 483, 532 Urethra, 501, 510, 532 Uricosuric, 508, 532 Urinalysis, 404, 425, 532 Urinary, 6, 99, 179, 247, 261, 353, 361, 439, 454, 468, 478, 497, 525, 532, 533 Urinary tract, 6, 353, 361, 439, 532, 533 Urinary tract infection, 362, 439, 532 Urinate, 532, 534 Urogenital, 403, 468, 533 Urogenital Diseases, 533 Urologic Diseases, 364, 533 Urticaria, 376, 533 Uterus, 429, 446, 455, 460, 489, 499, 509, 516, 531, 533 V Vaccination, 207, 223, 330, 533 Vaccine, 43, 96, 131, 330, 430, 511, 533 Vagina, 443, 446, 489, 516, 533 Vaginal, 375, 402, 424, 526, 533 Vaginitis, 443, 533 Valves, 3, 533
558 Lupus
Vasodilation, 476, 533 Vasodilator, 442, 457, 475, 533 Vasomotor, 463, 533 Vector, 113, 530, 533 Venom, 71, 184, 185, 331, 332, 338, 533 Venous, 10, 21, 51, 101, 143, 249, 260, 322, 331, 332, 436, 438, 497, 511, 533 Venous Insufficiency, 249, 533 Venous Thrombosis, 10, 331, 533 Ventricle, 438, 473, 512, 527, 528, 533 Ventricular, 104, 459, 533 Ventricular Dysfunction, 459, 533 Venules, 441, 443, 461, 534 Vertebrae, 523, 524, 534 Vertebral, 27, 235, 534 Vesicular, 473, 490, 534 Veterinary Medicine, 389, 534 Viral, 31, 55, 69, 74, 116, 319, 323, 331, 444, 460, 468, 479, 494, 517, 530, 534 Viral Core Proteins, 69, 534 Viral Load, 31, 534 Viral Proteins, 69, 534 Virulence, 530, 534 Visceral, 9, 249, 483, 503, 534 Viscosity, 441, 534 Visual field, 498, 511, 534 Vitamin A, 263, 479, 517, 534 Vitiligo, 64, 393, 534 Vitreous, 447, 483, 516, 534
Vitreous Body, 447, 516, 534 Vitro, 18, 19, 21, 28, 29, 32, 39, 43, 47, 49, 55, 65, 72, 74, 75, 76, 77, 78, 79, 83, 89, 95, 97, 99, 102, 108, 113, 144, 173, 245, 254, 327, 330, 332, 334, 336, 338, 441, 460, 468, 473, 478, 506, 520, 527, 534 Void, 377, 534 Vulgaris, 119, 139, 192, 213, 223, 258, 360, 361, 429, 534 W Weight Gain, 299, 323, 534 Windpipe, 503, 529, 535 Withdrawal, 144, 535 Womb, 516, 533, 535 Wound Healing, 445, 448, 488, 535 X Xenograft, 434, 535 Xerostomia, 415, 482, 535 X-ray, 27, 79, 295, 301, 303, 306, 308, 404, 451, 466, 481, 487, 496, 513, 514, 519, 524, 535 X-ray therapy, 481, 535 Y Yeasts, 443, 466, 503, 535 Z Zoster, 189, 220, 535 Zygote, 451, 535 Zymogen, 510, 535
Index 559
560 Lupus
