Granulomas: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

GRANULOMAS A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET R EFERENC...

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GRANULOMAS A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET

R EFERENCES

GRANULOMAS 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 2004 by ICON Group International, Inc. Copyright 2004 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., 1960Granulomas: 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: 0-497-00495-X 1. Granulomas-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.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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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 granulomas. 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 GRANULOMAS .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Granulomas................................................................................... 6 E-Journals: PubMed Central ....................................................................................................... 35 The National Library of Medicine: PubMed ................................................................................ 43 CHAPTER 2. NUTRITION AND GRANULOMAS ................................................................................ 87 Overview...................................................................................................................................... 87 Finding Nutrition Studies on Granulomas ................................................................................. 87 Federal Resources on Nutrition ................................................................................................... 91 Additional Web Resources ........................................................................................................... 91 CHAPTER 3. ALTERNATIVE MEDICINE AND GRANULOMAS .......................................................... 93 Overview...................................................................................................................................... 93 National Center for Complementary and Alternative Medicine.................................................. 93 Additional Web Resources ........................................................................................................... 99 General References ..................................................................................................................... 100 CHAPTER 4. PATENTS ON GRANULOMAS ..................................................................................... 101 Overview.................................................................................................................................... 101 Patents on Granulomas.............................................................................................................. 101 Patent Applications on Granulomas.......................................................................................... 104 Keeping Current ........................................................................................................................ 106 CHAPTER 5. BOOKS ON GRANULOMAS ........................................................................................ 107 Overview.................................................................................................................................... 107 Book Summaries: Federal Agencies............................................................................................ 107 Book Summaries: Online Booksellers......................................................................................... 108 Chapters on Granulomas ........................................................................................................... 108 CHAPTER 6. PERIODICALS AND NEWS ON GRANULOMAS ........................................................... 111 Overview.................................................................................................................................... 111 News Services and Press Releases.............................................................................................. 111 Academic Periodicals covering Granulomas.............................................................................. 112 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 115 Overview.................................................................................................................................... 115 U.S. Pharmacopeia..................................................................................................................... 115 Commercial Databases ............................................................................................................... 116 Researching Orphan Drugs ....................................................................................................... 117 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 121 Overview.................................................................................................................................... 121 NIH Guidelines.......................................................................................................................... 121 NIH Databases........................................................................................................................... 123 Other Commercial Databases..................................................................................................... 125 APPENDIX B. PATIENT RESOURCES ............................................................................................... 127 Overview.................................................................................................................................... 127 Patient Guideline Sources.......................................................................................................... 127 Finding Associations.................................................................................................................. 129 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 131 Overview.................................................................................................................................... 131 Preparation................................................................................................................................. 131 Finding a Local Medical Library................................................................................................ 131 Medical Libraries in the U.S. and Canada ................................................................................. 131

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ONLINE GLOSSARIES................................................................................................................ 137 Online Dictionary Directories ................................................................................................... 138 GRANULOMAS DICTIONARY ................................................................................................ 139 INDEX .............................................................................................................................................. 205

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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 granulomas is indexed in search engines, such as www.google.com or others, a non-systematic 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 granulomas, 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 granulomas, 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 granulomas. 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 granulomas, 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 granulomas. 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 GRANULOMAS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on granulomas.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and granulomas, 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 “granulomas” (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: •

Cherubism: Diagnosis, Treatment, and Comparison With Central Giant Cell Granulomas and Giant Cell Tumors Source: Oral Surgery, Oral Medicine, Oral Pathology. 73(3): 369-374. March 1992. Summary: Cherubism is a hereditary condition of the jaws that is characterized by bilateral expansion of the mandible and/or the maxilla that becomes noticeable during the first years of life, becomes progressively larger until puberty, and gradually resolves by middle age. The radiographic appearance is unique because of its diffuse, bilateral, multilocular nature, which retards the eruption of permanent teeth and may prevent the formation of permanent molars. This article presents an extensive case report of cherubism with no apparent familial involvement. The authors discuss its radiographic features, histopathologic appearance, and surgical management. In addition, the

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difficulty in distinguishing between cherubism, central giant cell granuloma, and giant cell tumor is discussed. 6 figures. 1 table. 33 references. (AA-M). •

Granulomas in Inflammatory Bowel Disease: Are They of Diagnostic or Aetiologic Significance? Source: European Journal of Gastroenterology. 4(1): 15-17. January 1992. Summary: Historically, the differentiation of various causes of granulomatous disease of the bowel has been difficult. This article considers the pathophysiology of the granuloma and the role of various etiological agents. The authors focus on the comparisons that may be made between Crohn's disease and intestinal tuberculosis. Topics covered include granuloma and granulomatous reactions in Crohn's disease and intestinal tuberculosis; granuloma formation; and the clinical implications of granulomas in tuberculosis and Crohn's disease. 1 table. 29 references.

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Gingival Plasma Cell Granuloma Source: Journal of Periodontology. 72(9): 1287-1290. September 2001. Contact: Available from American Academy of Periodontology. 737 North Michigan Avenue, Suite 800, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: Plasma cell granulomas (pseudo tumors) are rare, benign tumor-like proliferations composed chiefly of plasma cells that manifest primarily in the lungs, but may also occur in various anatomic locations. This article reports the case of a 54 year old male who presented with an unusual maxillary (upper jaw) anterior gingival (gums) overgrowth treated by excisional biopsy (removal of the growth). Histological examination revealed a dense inflammatory cell infiltrate containing mainly plasma cells. Immunohistochemistry for kappa and lambda light chains showed a polyclonal staining pattern confirming a diagnosis of plasma cell granuloma. Intraoral plasma cell granuloma is exceedingly rare, although case reports documenting such lesions have been reported. This case highlights the need to biopsy such unusual lesions to rule out potential neoplasms (cancer). 3 figures. 16 references.

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Gastrointestinal and Granulomatous Diseases Source: Periodontology 2000. Volume 18: 95-101. October 1998. Contact: Available from Munksgaard International Publishers Ltd. Commerce Place, 350 Main Street, Malden, MA 02148-5018. (781) 388-8273. Fax (781) 388-8274. Summary: The oral cavity arises from the primitive stomatodeum and is both ectodermal and endodermal in origin. It is therefore not surprising that, since the mouth is at the entrance to the gastrointestinal (GI) tract, a number of digestive diseases may also manifest in the mouth and that the gingiva and periodontium are sometimes involved. This article reviews how individual disorders specific to the GI tract may manifest as periodontal problems. The GI organs and diseases covered include the esophagus, stomach, liver, small intestine, large intestine, and ulcerative colitis. Granulomatous diseases (several of which manifest in the mouth) discussed include chronic granulomatous disease of childhood, Langerhans cell histiocytosis, bacterial infections (tuberculosis), fungal infections (deep mycoses), midline granulomas (Wegener's granulomatosis, peripheral T cell lymphoma), and orofacial lymphedema (local, Crohn's disease, and sarcoidosis). 9 figures. 1 table. 68 references.

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Contact Ulcers and Granulomas of the Larynx Source: Visible Voice. 2(2): 28-29,45-47. April 1993. Contact: Available from Center for Voice Disorders of Wake Forest University. Department of Otolaryngology, Bowman Gray School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1034. (919) 716-4161. Summary: This article discusses contact ulcers and granulomas of the larynx. The author discusses the etiology of these problems and considers the controversy surrounding the relative role of gastroesophageal reflux disease (GERD) and the diagnosis and treatment of contact ulcers and granulomas of the larynx. Topics covered include pathophysiology, including factors associated with endotracheal-tube-induced laryngeal damage; the clinical manifestations of vocal process granulomas and ulcers; and the therapeutic alternatives, including the medical treatment and surgical treatment for these conditions. One table outlines the diagnosis and treatment of laryngeal ulcers and granulomas. 2 figures. 1 table. 6 references.

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Pathology Consultation: Orofacial Granulomatosis and Crohn's Disease Source: Annals of Otology, Rhinology and Laryngology. 105(2): 166-167. February 1996. Summary: This article explores the pathogenesis of orofacial granulomatosis associated with Crohn's disease. The authors note that Crohn's disease is not responsible for all forms of orofacial granulomatosis, but the orofacial manifestations of the disease may herald its diagnosis. The clinical presentations of orofacial swellings and intraoral mucosal lesions are similar, regardless of etiology. So, too, are the histopathologic findings of noncaseating granulomas, edema, and chronic lymphoproliferative infiltrate. Topics include the macroscopic features of oral Crohn's disease, its incidence and prevalence, etiologic considerations, and treatment options. Various treatments, including topical, intralesional, and systemic medications, have been used for Crohn's disease. Systemic corticosteroids improve the oral ulcerations and swelling of the lips, but are less effective for the buccal mucosal cobblestoning. Oral surgery is not warranted because of the recurrences of the oral lesions and the lack of proof of benefit. 1 table. 8 references. (AA-M).

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Pyogenic Granuloma Subsequent to Apical Fenestration of a Primary Tooth Source: JADA. Journal of the American Dental Association. 133(5): 599-602. May 2002. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: This article presents two case reports of patients exhibiting pyogenic granulomas in the maxillary labial mucosa, which were related to an apical fenestration (a perforation of the labial bone and mucosa plate) of a primary incisor. After the extraction of a fenestrated primary tooth, the gingival (gum) wound and the surrounding inflammatory tissue typically heal spontaneously. However, in these two girls, the surrounding gingival lesions did not heal after the teeth were extracted. The authors recommend that after extracting fenestrated teeth, clinicians need to examine the labial area at a follow up appointment to ensure that the gingival hyperplasia heals properly. The authors suggest performing curettage of the surrounding abnormal tissue at the time of the tooth extraction. 6 figures. 15 references.

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Warthin's Tumor with Multiple Sarcoid-Like Granulomas: A Case Report Source: Journal of Oral and Maxillofacial Surgery. 60(5): 585-588. May 2002. Contact: Available from W.B. Saunders Company. Periodicals Department, P.O. Box 629239, Orlando, FL 32862-8239. (800) 654-2452. Website: www.harcourthealth.com. Summary: Warthin's tumor (papillary cystadenoma lymphomatosum) is the second most common benign (non-cancerous) neoplasm of the parotid gland (a salivary gland) and constitutes about 14 percent of all epithelial tumors of the parotid gland. This article reports the case of a patient with Warthin's tumor with an unusual granulomatous lymphoid stroma involving both the tumor and the adjacent non-neoplastic (without new growth) salivary gland. Eight weeks after fine needle aspiration, superficial parotidectomy was performed for excision of the tumor. A peculiar feature was the presence of many sarcoid-type granulomas composed of dense aggregates of epithelioid histiocytes and occasional Langhan's giant cells. At 2 years of follow up, the patient remained asymptomatic with no signs or symptoms indicating a systemic ongoing disease process. The authors note that the coexistence of Warthin's tumor with granulomas is an unusual and rarely reported phenomenon. 2 figures. 17 references.

Federally Funded Research on Granulomas The U.S. Government supports a variety of research studies relating to granulomas. 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 granulomas. 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 granulomas. The following is typical of the type of information found when searching the CRISP database for granulomas: •

Project Title: A NON-HUMAN PRIMATE MODEL OF TUBERCULOSIS AND AIDS Principal Investigator & Institution: Flynn, Joanne L.; Associate Professor; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 30-JUN-2004 Summary: Tuberculosis causes almost 3 million deaths per year worldwide. A vaccine effective against tuberculosis is essential to control or elimination of this disease. Great strides have been made in our understanding of the immune responses important in protection against this disease, and this knowledge is fundamental in the design of a vaccine. A non-human primate model for tuberculosis would provide answers to many

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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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questions about immune responses to M. tuberculosis as well as provide an animal model for testing vaccines and drugs. Results obtained in such a model may be relevant to human studies. Here we propose three specific aims: 1) establishment of a nonhuman primate model for tuberculosis; 2) assessment of immunologic correlates of tuberculosis in a non-human primate model; and 3) the effect of coinfection with M. tuberculosis and SIV on progression to AIDS, as well as reactivation of latent tuberculosis. Monkeys with tuberculosis can be quite infectious to humans and to monkeys. A primate Biosafety Level 3 facility will be outfitted so that appropriate and safe techniques are used in these studies. We will compare rhesus macaque and cynomolgus monkeys with respect to the ability to control a low dose (10 CFU, delivered to the lungs via bronchoscope) virulent M. tuberculosis infection, to determine whether a subset of animals of either species can control the infection in a chronic (or latent) state. Establishment of a non-human primate model for tuberculosis allows one to obtain tissue not generally available from human studies, including lung tissue and granulomas at various times post-infection. Monkeys in these studies will be used to study localized immune responses to tuberculosis, i.e. T cells, macrophages and cytokines in the pulmonary granulomas at various times post-infection, using a variety of techniques. The rhesus or cynomolgus monkey may provide an excellent model for studying tuberculosis, including protective immune responses, but also provides a model for studying the interaction of two important pathogens: M. tuberculosis and HIV. Understanding this interaction, including the immunologic responses that occur during co-infection is key to the eventual control of these diseases. We will co-infect monkeys with SIV and M. tuberculosis to determine the effect that tuberculosis, and the chronic immune stimulation that accompanies it, has on SIV infection and progression to AIDS. Various immune parameters of localized responses in the co-infected monkeys will also be tested. Once a non-human primate model for tuberculosis is established, it could be used to test vaccines, immunotherapy, and new treatment options for tuberculosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI TUBERCULOSIS CANDIDATE VACCINE TESTING IN RHESUS MONKEYS Principal Investigator & Institution: Gormus, Bobby J.; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002 Summary: Eight normal RM were inoculated with MTB via fiberoptic bronchoscope. Four received the less virulent H37Rv strain and four received the highly virulent Erdman strain via fiberoptic bronchoscope. Both monkeys that received the high dosage of H37Rv (6 X 106 cfu) developed extensive multifocal expansile and coalescing granulomas with broad central zones of necrosis, neutrophilic infiltration, and mineralization in the inoculated right lobe of the lung by 5 and 11 weeks (wk) postchallenge. Monkeys receiving the low dose of H37Rv (30 cfu) had granulomatous lesions in the bronchial lymph nodes 18 wk after infection. Lesions suggest that low doses of M. tuberculosis H37Rv are controlled, at least in the short term, by natural defenses in the simian lung and that challenge with higher doses of bacteria produces significant tissue response without evidence of septicemic spread. Two high dose (150 cfu) Erdman recipient monkeys developed extensive granulomatous pneumonia, pleuritis, and bronchial node necrosis with microgranulomas in the liver, kidney, and other sites in 7-9 weeks. The appearance of pneumonia and time course were roughly comparable to disease produced by high dose (>106) H37Rv. The 2 low dose Erdman-

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inoculated monkeys (15 cfu) remained clinically normal 9 weeks post-challenge and at 19 wk had minimal clinical manifestations, but fibrotic granulomatous pulmonary lesions with spread to other tissues. We conclude that chronic disease can be established by low dose Erdman inoculation with a wider distribution of lesions being produced compared to the H37Rv strain. FUNDING Base Grant, Venture Research PUBLICATIONS Didier PJ, Blanchard JL and Gormus BJ. Pulmonary Tuberculosis in Normal Rhesus Monkeys Produced by M. tuberculosis H37Rv. Am J Soc Trop Med Hyg 57:156, 1997 [Abstract]. Didier PJ, Blanchard JL and Gormus BJ. Chronic Tuberculosis Produced by Low Dosage of M. tuberculosis (Erdman) in Rhesus Monkeys. Am J Soc Trop Med Hyg 59:361, 1998. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGEN

CD1-RESTRICTED

T

CELLS

AGAINST

THE

TULAREMIA

Principal Investigator & Institution: Sieling, Peter A.; Associate Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2004; Project Start 15-FEB-2004; Project End 31-JAN-2006 Summary: (provided by applicant): The tularemia pathogen, Francisella tularensis, is a highly virulent human pathogen and is easily transmitted through aerosols, thus its potential for use as a weapon of bioterrorism is high. The bacterium is a facultative intracellular pathogen, suggesting a crucial role for T cells in protective immunity against the organism as has been confirmed by studies in animal models. T cells contribute to protection against microbial infection by recognizing peptides presented by major histocompatibility complex (MHC) molecules and lipids presented by the MHC-like CD1 proteins. T cells reactive with peptide antigens from F. tularensis have been studied in both animal models and humans. However, T cell responses to the lipid antigens of F. tularensis have not been investigated. Lipids within the cellular envelope of Francisella species contain unusual hydroxy and long chain fatty acids, two components characteristic of lipid antigens from Mycobacterium species presented by CD1. In addition to its lipid chemistry, F. tularensis displays a number of other similarities to Mycobacterium tuberculosis in its site of intracellular growth, formation of granulomas by the host, and requirement for T cell function and IFN-gamma, production for protective immunity. Our overall hypothesis is that Francisella tularensis contains lipid antigens for the CD1 antigen presentation pathway and that F. tularensisreactive CDl-restricted T cells contribute to the control of tularemia infection. We first propose to establish human CDl-restricted T cells that recognize lipid antigens of F. tularensis and identify the structure of lipids that stimulate CDl-restricted T cells. Second, we will determine the function of F. tularensis-reactive human CDl-restricted T cells. Protective immunity against F. tularensis requires IFN-gamma, production and individuals vaccinated against F. tularensis infection generate antigen-specific cytotoxic T cells (CTLs). CDl-restricted T cells against microbial lipids produce IFN-gamma and function as CTLs against infected macrophages. We propose to determine the cytokine pattern of F. tularensis-reactive CD1- restricted T cells and whether F. tularensis-reactive CDl-restricted T cells lyse bacteria-infected macrophages to reduce the bacterial load. From these studies we hope to expand the diversity of lipid antigens known to activate CDl-restricted T cells with the future goal to design lipid-based vaccines against tularemia infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHARACTERIZATION OF ACID INDUCED PROMOTERS OF M. TB Principal Investigator & Institution: Saviola, Beatrice J.; Basic Medical Sciences; Western University of Health Sciences Health Sciences Pomona, Ca 917661854 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2005 Summary: (provided by applicant): Tuberculosis exacts an enormous burden in morbidity and mortality on the global population. With the advent of the HIV epidemic and multiple drug resistances, disease due to tuberculosis has increased leading to a need for research into the basic mechanisms of pathogenesis. The long-range goal of this proposal is to understand how Mycobacterium tuberculosis, the causative agent of tuberculosis, can sense environmental stresses, up regulate critical genes, and survive in the hostile environment of the host. When M. tuberculosis invades a host it infects human macrophages. M. tuberculosis can also be found within host granulomas that have been shown to have an acidic pH. The putative promoter regions of the M. tuberculosis genes lipF and Rv0834c have been identified to be upregulated in response to acidic pH. The specific aims of this proposal are to: 1) characterize the putative promoter regions of lipF and Rv0834c to better understand how acid induced promoters are regulated 2) determine if lipF and Rv0834c are required for mycobacteria to resist acidic stress and identify additional stresses which may upregulate these genes. The expectation is that this work will result in the characterization of acid responsive promoter regions and provide the groundwork for the eventual identification of a general mechanism by which M. tuberculosis can resist environmental stresses such as acidic stress. This work is significant because it will contribute to a greater understanding of mycobacterial stress response and ultimately survival and persistence in the host during infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHARACTERIZATION OF TOXICITY WITH SPINAL OPIATES Principal Investigator & Institution: Yaksh, Tony L.; Professor; Anesthesiology; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Continuous intrathecal infusion of concentrated morphine is widely used in pain therapy. Surprisingly, until recently there has been no study of the safety of such infusions. We investigated the effects of 28-day intrathecal morphine infusion in a canine model. Unexpectedly, at high morphine concentrations (as used in humans), we noted an aseptic mass of inflammatory cells (granuloma) arising from the dura-arachnoid, not the parenchyma, proximal to the catheter tip. Granulomas were not seen with vehicle or a variety of non-opioid agents. The alpha2 adrenergic agonist clonidine suppressed the granuloma. These observations lead to four hypotheses. 1. Granuloma induction by morphine is proportional to local concentration in cerebrospinal fluid and not simply total dose. 2: Effect is mediated by an opioid agonist action and is not limited to morphine. 3. The granuloma results from a local degranulation of dural mast cells leading to movement of inflammatory cells from the dural vessels. Accordingly, granuloma-inducing potency will be proportional to the ability to degranulate dural mast cells in ex vivo dural preparations. 4. Granulomainducing effects and dural mast cell activation are suppressed by local alpha2 receptor agonists and by a mast cell stabilizer. We will address these hypotheses using the canine model to examine the effects of continuous intrathecal infusion of equipotent doses of mu opioid agonists (morphine, morphine-6-glucuronide, L-methadone, hydromorphone, fentanyl or DAMGO) or equimolar concentrations of inactive opioid

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molecules (naloxone, morphine-3-glucronidc, D-methadone). In vivo treatment with a mast cell stabilizer, nedocromil sodium, will be examined for its effect on granuloma formation. In parallel studies, kinetics studies will permit comparisons based on measured CSF concentrations. Interaction between morphine and alpha2 agonists (clonidine, dexmedetomidine) will be studied by co-delivery. Granuloma formation and local mast cell degranulation and cytokines will be assessed histochemically and by CSF analysis. In summary, our initial work, provides the first definitive preclinieal data defining the effect, the attenuation by clonidine, and a novel mechanistic hypothesis for drug-induced degranulation of dural mast cells which suggests a novel method for the ex vivo screening of new agents. These studies are significant: 1) increasing incidence of reports of morphine-granulomas emphasize it is not rare; 2) our investigation of other opioids provide the first time assessment of the spinal safety of agents which are now in wide clinical use; and 3) this issue impacts on all agents targeted for intrathecal delivery. Accordingly, data obtained here regarding the role of local CSF concentration, the safety of non-morphine agents and the potential ameliorating effects of adjuvant agents all provide novel information to refine the utility of this important therapeutic regime. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FORMATION

CHEMOKINE

RECEPTOR

DYNAMICS

IN

GRANULOMA

Principal Investigator & Institution: Chensue, Stephen W.; Pathology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-AUG-1998; Project End 31-MAR-2007 Summary: (provided by applicant): Hypersensitivity-type granulomas (GR) are T cellmediated chronic inflammatory lesions observed in a wide variety of infectious and noninfectious diseases often causing serious morbidity and mortality. Understanding the manner in which T cells participate and promote theses lesions will aid the development of interventions. These lesions can be classified as type-1 or type-2 based upon the relative participation of Th1 and Th2 associated cytokines. The current paradigm is that Th1 and Th2 CD4+ helper cells are recruited to inflammatory sites by chemokines (CK) and show selective migration by virtue of differential chemokine receptor expression. Using animal models of synchronized, type-1 and type-2 pulmonary GR formation elicited respectively by protein antigens of Mycobacteria tuberculosis and Schistosoma mansoni, we found indications of both shared and polarized CK receptor expression among type-1 and type-2 CD4+ memory helper cells as well as antigen stimulated regulation. However, the in vivo significance and contribution of these findings to GR formation is unknown. The present proposal will extend this work and test the hypothesis that effector Th1 and Th2 cells are recruited to inflammatory sites by way of innate phase chemokines through polarized postactivation chemokine receptors. The specific aims will employ state-of-the-art laser capture microdissection (LCM) and real time, gene sequence detection technologies to reveal the microenvironmental expression and function of Th cell CK receptors. Aim 1 will use LCM to define the temporal expression and tissue compartmental location of CK transcripts during synchronous Ag-bead and asychronous infectious type-1 and type-2 GR in order to allow correlation to T cell CK receptor expression. Aim 2 will determine the distribution of induced CK receptor transcripts among effector Th1 and Th2 cells generated in vivo. Aim 3 will reveal the potential biologic contribution Aginduced receptors such as CXCR3, CCR4 and CCR8 to selective Th migration using direct chemotaxis of antigen-activated CD4+ T cells. Aim 4 will define the temporal expression of CK receptor transcripts within the tissue microenvironments during

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synchronous Ag-bead and asychronous infectious type-1 and type-2 GR formation. Finally, Aim 5 will examine the migratory behavior of adoptively transferred CD4+ T cells with targeted CK receptor knockout and concomitant transgenic expression of green fluorescent protein (GFP). These studies will potentially provide novel and important information regarding the contribution of CK receptors to CD4+ T trafficking in chronic inflammatory responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CORE--MORPHOLOGY Principal Investigator & Institution: Johnson, Kent J.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: This core is a central morphology facility providing support for the investigators in the program project. The services provided include routine light microscopy processing, analysis of tissue sections, and special stains. In addition, where desired by the investigators, transmission electron microscopy (TEM), immunofluorescence, immunohistochemistry, and morphometric analysis services are available. Finally, this core provides digital image analysis and graphic illustration support for the investigators. In the past this core has received heavy usage and it is anticipated that demand will continue to increase. For example, during this past year over 2100 samples were processed for the sections of the program project. Of this total there were 1640 samples submitted for light microscopy analysis, 305 samples for immunohistochemistry and/or immunofluorescence studies and 181 samples for TEM. We anticipate that there will be heavy usage of this core by the investigators in the coming years. For example, in sections I, II, III, and IV light microscopy will be routinely used to monitor the intensity of the lung injury in various models. In addition, in vitro studies of isolated cells and tissue culture monolayers will be done in all sections using this technique. TEM studies will also be used extensively in this program project with all of the sections utilizing this technique. Morphometric analyses of tissue alterations utilizing primarily TEM will be done on selected tissues for sections II, III, and IV. Morphometric analysis is required to precisely quantitate injury to the lung with such parameters as percent alveolar and endothelial cell injury and quantitation of leukocytes and hemorrhage evaluated routinely by this method. In addition section II will use morphometry to evaluate the size and distribution of the granulomas in the lung. Frozen sections analysis of tissues and cells, particularly for immunohistochemistry studies, is heavily utilized currently by investigators and this will continue in the current proposal. Immunohistochemistry is the primary technique used for evaluating adhesion molecule and cytokine up-regulation in vivo and in vitro and will be utilized by all sections of the program project. Selected immunofluorescence studies will also be done utilizing frozen sections to evaluate immune complex induced lung injury and the effect of interventional studies primary in section 1. Finally, the core facility offers digital image analysis and graphic services including color digital laser printing for posters and publications for investigators in the program project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ETIOLOGIC ANTIGENS IN SARCOIDOSIS Principal Investigator & Institution: Moller, David R.; Associate Professor of Medicine; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007

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Summary: Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that involves the lungs in over 90 percent of affected individuals and may cause endstage fibrosis, cor pulmonale, and death. The pathologic hallmark of sarcoidosis is noncaseating granulomatous inflammation. Since extracts of diseased tissue injected intradermally elicit a nidus of granulomatous inflammation in patients with sarcoidosis that is indistinguishable from spontaneously arising granulomas (the Kveim reaction), we postulate that sarcoid tissue extracts contain disease-relevant antigens. Biophysical properties of the active component in Kveim extracts include relative heat stability, resistance to neutral detergents and proteases, and a dependence on tertiary structure. The overall goal of this application is to identify these pathogenic tissue antigens in sarcoidosis. Our central hypothesis is that sarcoidosis is caused by linked T and B cell immune responses to aggregates of altered proteins of microbial origin. Consistent with this hypothesis, our preliminary studies demonstrate the presence of a small number of protease-resistant, neutral-detergent insoluble proteins that by immunoblot analysis are targets of T cell dependent IgG from patients with sarcoidosis but not healthy controls. MALDI-TOF mass spectrometry and immunoblot analysis has identified the mycobacterial catalase-peroxidase protein from Mycobacterium tuberculosis (mKatG) or M. smegmatis in these protein fractions from sarcoidosis but not control tissues. Preliminary studies demonstrate both T and B cell responses to mKatG proteins in sarcoidosis, suggesting the mKatG proteins are relevant, pathogenic antigens in sarcoidosis. To test the hypothesis that mycobacterial KatG proteins are pathogenic antigens in sarcoidosis, we propose studies to determine the presence of mycobacterial KatG proteins in sarcoidosis and control tissues using MALDI-TOF mass spectrometry and protein immunoblot analyses. To determine whether these microbial proteins induce disease-specific immune responses, we will determine the molecular basis of the B and T cell immune responses to both M. tuberculosis and M. smegmatis KatG proteins and selected peptides, and determine whether mKatG proteins preferentially expand specific Valpha/Vbeta expressing T cells in patients with sarcoidosis and control subjects. Together, these studies offer the potential of identifying a specific group of microbial antigens involved in the pathogenesis of granulomatous inflammation in sarcoidosis, thus providing a novel target for therapy of this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FCR DEFICIENT MICE SUSCEPTIBILITY TO PATHOGENS Principal Investigator & Institution: Ravetch, Jeffrey V.; Theresa & Eugene M. Lang Professor; Lab/Molec Genetics & Immunol; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002; Project Start 01-MAY-1994; Project End 31-JAN-2004 Summary: Knowledge of the relative contributions of innate and adaptive immunity in host resistance to pathogens is essential both to an understanding the basic immunological mechanisms involved and in the design of effective immunotherapies. We have employed targeted gene disruption approaches to define the role of specific components of the antibody- effector cell pathway in host susceptibility to the encapsulated fungus Cryptococcus neoformans and the trematode Shistosoma mansoni. Mouse strains deficient in the activation subunit of Fc receptors, FcRgamma, have significant defects in type I, II and III inflammation, and manifest specific alterations in their responses to these pathogens. In C. neoformans the role of IgG/FcgammaR interactions has been studied in a model of passive immunotherapy employing IgG switch variants of an anti-capsular GXM antibody. Thus, IgG1 antibodies are protective and require the expression of FcRgamma chain while IgG3 antibodies enhance infection

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in both FcRgamma-/- and wild-type strains, implying the existence of a novel IgG3 FcR. We will pursue these observations to determine 1) The contribution of individual FcRs on specific effector cells to the sub-class differences in protection, 2) The structure of the IgG3 FcR and its relationship to the known FcRs and 3) The signal transduction pathways triggered by IgG3 binding to its FcR. In S. mansoni infection, pathology results from sensitized CD4 cells triggering granuloma formation, fibrosis and subsequent circulatory impairment. B cell deficient animals or animals lacking FcRgamma show enhanced tissue responses to egg deposition. Egg granulomas are larger and fail to undergo down-modulation during the chronic phase of infection in both deficient strains. These studies suggest a novel and previously unappreciated role for antibody-FcR interactions in modulating T cell mediated reactions. In addition, B cell deficient mice are impaired in their ability to excrete eggs, independently of FcRgamma expression. We propose to extend on these results by 4) Characterizing the specific FcRs and effector cells responsible for the enhanced granuloma response, 5) Determining the antibody receptors responsible for egg excretion and 6) Investigating the generality of antibody-FcR interactions as modulators of T cell responses by characterizing contact sensitivity and DTH reactions in FcR deficient animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE EXPRESSION PROFILING OF THE KVEIM SILTZBACH TEST Principal Investigator & Institution: Iannuzzi, Michael C.; Associate Professor; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2004; Project Start 09-JUL-2004; Project End 30-JUN-2006 Summary: (provided by applicant): Approaches to define early gene expression in sarcoidal granuloma formation have been limited. No animal model for sarcoidosis exists and human studies have been carried out in patient samples obtained at diagnosis or during the disease course. Previous studies performed at Mt. Sinai and elsewhere have shown that the cellular and biochemical granulomatous response to KveimSiltzbach (KS) suspension parallels the disease granuloma. Studies of KS injected tissue harvested at weeks 1, 2, 3 and 4 have revealed recruitment of CD4 lymphocytes and macrophages that gradually form the mature epithelioid cells, giant cells, and rim of lymphocytes that form the sarcoidal granuloma. There are no studies of the temporal sequence of gene expression during this time period as granulomas emerge. Gene expression microarray analyses during Kveim maturation offer a unique opportunity to investigate the cascade of molecular biologic events leading to granuloma formation. We propose to recruit 5 to 8 patients who recently had positive KS tests for the diagnosis of their illness. Four subcutaneous injections will be performed. Sites will be biopsied a 1 day, 1 week, 2 weeks, and 4 weeks after incubation of KS suspension. For controls each patient will have a biopsy of normal skin. Gene expression profiles will be determined by microarray analysis and related to histological changes. Gene expression results by microarray will be verified by RT PCR and immunohistochemisty. Identifying genes expressed in response to the KS suspension will provide new information about the initiation of granuloma formation, give greater direction to future studies and could help identify new potential targets for intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE KNOCK-OUT MICE AS MODELS FOR THE LEPROSY SPECTRUM Principal Investigator & Institution: Adams, Linda B.; Associate Professor; National Hansen's Disease Program 1770 Physician Park Dr Baton Rouge, La 70816

14

Granulomas

Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2007 Summary: (provided by the applicant): The proposed studies will explore Mycobacterium leprae foot pad infection in knockout (KO) mouse strains carefully selected for their disruption in genes that play key roles in host cell mediated immunity (CMI) to mycobacterial pathogens. Growth of M. leprae in the foot pad will be monitored and the experimental granulomas which develop will be analyzed to determine if these KO mouse strains can serve as models for the key immunoregulatory elements of CMI that result in the unique immunopathological spectrum of human leprosy. CMI responses will be further modified in the KO mice by conditionally knocking-out additional gene products before or after infection with M. leprae or by selectively restoring certain disrupted gene functions after infection. Development of KO mouse models for discrete elements of the human leprosy spectrum should open investigation into the mechanisms underlying the instability inherent to the borderline area of this spectrum where downgrading and upgrading shifts toward the lepromatous and tuberculoid ends of the spectrum, respectively, are poorly understood. More importantly, KO mouse models of leprosy and the additional manipulations of these models that are proposed may afford insight into the mechanisms responsible for the abrupt onset of type 1 and type 2 reactions. Ultimately, this basic knowledge may permit prediction and prevention of these devastating reactions, which markedly enhance nerve damage. Numerous studies have been reported with M. tuberculosis in gene KO mice. We suggest that M. leprae-KO mouse studies will permit more detailed dissection of the mechanisms of CMI. Targeted removal of a number of isolated gene functions often greatly exacerbates experimental murine tuberculosis, perhaps by overwhelming certain compensatory mechanisms in host resistance. In marked contrast, M. leprae is a quiet, well adapted, obligate intracellular pathogen. This proposal is based on the likelihood that its characteristics of slow rate of growth, low virulence and chronic pathogenesis are the very attributes which will make the study of M. leprae in targeted gene KO mice an ideal model for analyzing the principal redundant and compensatory mechanisms of CMI in host resistance to infection in general and to intracellular mycobacterial pathogens in particular. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC SUSCEPTIBILITY TO CHRONIC BERYLLIUM DISEASE Principal Investigator & Institution: Gordon, Terry; Associate Professor; Physiology and Neuroscience; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2003; Project Start 10-APR-2003; Project End 31-JAN-2007 Summary: (provided by applicant): This research proposal will examine the role of host genetic factors in the adverse pulmonary effects of inhaled beryllium. Investigators have clearly demonstrated that only a portion of exposed workers develop chronic beryllium disease (CBD). The reason for the variability in response to inhaled beryllium is not known, but strong evidence suggests that inter-individual differences in the molecular coding for immune system proteins play a major role. Using a gene-by-gene research approach, investigators have shown that one or more nucleotide polymorphisms in HLA are significantly associated with the development of CBD. These molecular epidemiology studies have focused on genetic differences in the major histocompatiblity complex, thus ignoring the potential role of other genes to explain the variability in response to beryllium-induced CBD. Moreover, in addition to modifying genes, environmental factors such as dose and speciation of beryllium are believed to play significant roles in the induction of CBD. Thus, an understanding of the gene

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environment interaction is critical in clarifying the mechanism(s) of host response to beryllium exposure. A predictive genetic animal model of inter-individual variation for CBD will permit the dissection of the factors of genes and environment in CBD. Although genetic studies in mice and guinea pigs have previously suggested inter-strain variability in the response to beryllium, a systematic and complete genome wide search for susceptibility genes for CBD has not been conducted. We will directly address this research gap by examining the response of genetically homogeneous, inbred strains of mice exposed to beryllium using a murine model of beryllium-induced lung granulomas. The primary objectives of this project are: 1) to test the hypothesis that there is a genetic basis for the induction of CBD in response to inhalation of beryllium aerosols; 2) to quantify the contribution of genetic versus environmental factors; and 3) to identify candidate genes that play a critical role in the molecular pathways leading to CBD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF HOST RESISTANCE & SUSCEPTIBILITY TO TB Principal Investigator & Institution: Kramnik, Igor; Assistant Professor of Immunology & Infe; None; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-1997; Project End 31-JUL-2007 Summary: (provided by applicant): A significant variation in susceptibility to tuberculosis among immunocompetent individuals is partially explained by genetic heterogeneity within the host population. However, precise mechanisms of the genetic control of anti-tuberculosis immunity are unknown. We employ a mouse experimental model of tuberculosis for the genetic analysis of the naturally occurring variation in tuberculosis resistance among immunocompetent inbred mouse strains to identify and isolate genes important for determining susceptibility to this infection. We have previously mapped the sstl locus, which controls progression of pulmonary tuberculosis early after infection. Using the sst1-resistant congenic mice we mapped six new quantitative trait loci (QTL) that control variation in tuberculosis resistance among the sstl-resistant hosts. Functional expression of some of those loci is sstl-dependent. We will study the new loci and characterize their possible interactions using genotypeassisted breeding and advanced backcross-intercross progeny testing in order to narrow candidate intervals and establish conditions for their further genetic dissection. We will generate a set of congenic strains by transferring new candidate QTLs on a C3H background and dissect those loci into smaller chromosomal segments to facilitate positional cloning. Using new congenic strains we will study cells that form lung granulomas in resistant and susceptible animals. Identify correlates of tuberculosis resistance and susceptibility at molecular level and establish proxy phenotypes for each locus that can be used as surrogate biomarkers for predicting genetic susceptibility in segregating populations. Identification of molecules encoded in QTLs will help explain critical functional differences conferred by the genetic polymorphisms on mechanisms of host resistance to tuberculosis at both systemic and lung-specific levels. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GRANULOMATOUS LUNG INFLAMMATION Principal Investigator & Institution: Kunkel, Steven L.; Endowed Professor in Pathology Research; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274

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Granulomas

Timing: Fiscal Year 2002 Summary: The initiation and maintenance of chronic pulmonary inflammation is due to a dynamic interaction between an inciting agent, inflammatory mediators, leukocytes, and structural cells of the lung. Independent of the etiology granulomatous lung disease usually possess specific pathologic responses, which are characterized by th elicitation and activation of various leukocyte populations to define areas of the lung. The specific objective for this section of the Program Project is to determine the mechanisms whereby the expression and regulation of either a type 1 or type 2 cytokine phenotype. The following hypothesis will be addressed to support this objective: Recruitment and activation of various leukocyte populations to granulomatous lesions supported by specific chemokine receptors. As leukocytes traffick to sites of granulomatous inflammation, they are influenced by cytokines and other mediator systems, which dictate the expression of chemokines and chemokine receptors. The expression of chemokine receptors are important in "sampling" the environment for chemokine family members which are key for specific leukocyte activation events and continued recruitment. The proposed studies will focus on the following questions: 1) What are the mechanisms involved in the expression of CC type 1 (Th1) or type 2 (Th2) cytokines)? 2) what alterations in the normal development of these lung granulomas are found in CCR1, CCR2, CCR3, or CCR5 knockout mice? 3) What are the chemokine/chemokine receptor- dependent mechanisms by which normal lung fibroblasts or fibroblasts isolated from either type 1 or type 2 granulomas can regulate leukocyte reactivity during granuloma development? and 4) What is the role of cell- to-cell interactions which dictate chemokine and chemokine receptor expression during granuloma development? The expression of chemokines and chemokines and chemokine receptors and mechanisms that regulate their expression will be studied using well characterized models of lung inflammation in normal and knockout mice via bioassays, ELISAs, immuno- histochemistry, Northern blot or RT-PCR, and in situ hybridization analyses. The studies designed in this proposal will show that chemokines and their receptors play novel roles in the initiation and maintenance of pulmonary inflammation and will serve as excellent targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST RESPONSES TO MYCOBACTERIUM INFECTION IN ZEBRAFISH Principal Investigator & Institution: Ramakrishnan, Lalita; Assistant Professor; Microbiology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Tuberculosis is the leading cause of death from infectious diseases worldwide, with increasing consequences due to the HIV epidemic. The existing vaccine, BCG, has marginal efficacy. Infection and disease are caused by the intracellular bacterial pathogen Mycobacterium tuberculosis. In the face of a complex immune response, the bacteria can persist indefinitely in granulomas, tight aggregates of highly differentiated macrophages and other immune cells. As with most infectious diseases, the impact of the different aspects of host immunity on tuberculous infection and disease are not well understood. To better understand the host responses to tuberculous infections, we will exploit the fact that Mycobacterium marinum, a close relative of M. tuberculosis is a natural pathogen of zebrafish, causing a tuberculosis-like disease. Zebrafish are genetically tractable vertebrates that are used as models of disease and development. We have exploited the optical transparency of the zebrafish embryo to visualize M. marinum infection of embryonic macrophages in real time. The infection

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parallels adult tuberculosis in many ways. We will use the zebrafish-M, marinum infection model to study the role of host immune genes in infection. We will use whole mount in situ hybridizations to determine which host immune markers thought to be important in tuberculosis, are expressed in the developing embryo. We will determine if their expression is changed during infection. We will inactivate these genes using morpholino technology and determine by real time visualization when and how they act in infection. We will determine their role for the different facets of infection, from early macrophage migration in response to M. marinum to granuloma formation. The ability to visualize infection in real time in zebrafish embryos with functional inactivation of individual host genes will allow us to study the role of the host immune system in unprecedented detail. The proposed experiments will inherently yield new information about the role of various immune genes in zebrafish development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST-PATHOGEN GENE EXPRESSION DURING A PULMONARY MYCOBAC Principal Investigator & Institution: Lyons, C. Rick.; Associate Professor; Medicine; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Mycobacterium tuberculosis (Mtb) is a significant threat to both immunocompromised and immunocompetent populations. Mtb is an intracellular organism with an extremely complicated life cycle involving resistance to normal host defense mechanisms and subsequent development of a latent state. Similarly, the host response to Mtb infection is a complex series of immune events resulting in granulomatous inflammation to control Mtb proliferation with subsequent formation of granulomas that maintain Mtb in a latent state. The development of drug resistant Mtb strains has made the understanding of its pathogenesis a high priority in order to identify potential targets for antibiotics and immunomodulatory interventions. The recent sequencing of the Mtb genome has provided an exciting database for aiding in dissecting Mtb pathogenesis. Together with the application of microarray technology to in vivo infections, there is the potential for an analysis of genome wide expression during different stages of infection. We hypothesize that during the dynamic interactions between the host and the Mtb there is a series of changes in the environment that lead to differential expression of genes that enhance survival for both the host and the Mtb. We intend to use microarray analysis to determine the gene expression that occurs during a pulmonary infection with Mtb in the mouse. We will use arrays that contain all open reading frames of the Mtb genome as well as an array containing approximately 100 immunoresponsive murine genes. This will allow us to correlate changes in the host that result in changes in the organism. Finally, we will use an in vivo luciferase based technology to track Mtb infections and gene expression in real time. The development of this model will provide a high through put system for testing therapeutic interventions using fewer mice than standard assays as well as significantly enhance our ability to monitor specific Mtb gene expression in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IL-16 IN PULMONARY CRYPTOCOCCOSIS Principal Investigator & Institution: Kornfeld, Hardy; Professor; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007

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Summary: (provided by applicant): Interleukin-16 (IL- 16) is a structurally unique cytokine that uses CD4 as a receptor to signal diverse biological activities in target cells including but not limited to T cells, monocytes, dendritic cells and eosinophils. Initially described as a chemoattractant factor for CD4+ T cells, IL-16 was later found to upregulate IL-2Rcz and HLADR expression, and to cause reversible anergy of CD4+ T cells in vitro. A role for IL-16 in pathological immune responses is suggested by its presence in a variety of diseases characterized by CD4+ T cell accumulation including asthma, sarcoidosis, inflammatory bowel disease, and rheumatoid arthritis. In some disease states, epithelial cells or fibroblasts express IL-16. A role for IL-16 in host defense is suggested by elevated blood levels in HIV-infected hosts, and by its expression in tuberculous granulomas. The biological activities described for IL-16 in vitro suggest that it could function either as a pro-inflammatory or anti-inflammatory cytokine in vivo. We cloned the murine IL-16 gene and used it to create an IL- 16 knockout mouse. In this application, we propose to challenge the IL-16 knockout mouse by experimental infection with Cryptococcus neoformans to learn how IL-16 functions within the integrated immune response in vivo. Preliminary data suggest that IL-16-/- mice fail to control pulmonary C. neoformans infection despite mounting an exuberant inflammatory response. We will investigate the specific deficits displayed by IL-16-/mice in both the T cell and macrophage components of cell-mediated immunity, and we will examine the role of IL-16 expression by bronchial epithelial cells in host defense. Our research plan capitalizes on a well-characterized mouse model of cryptococcal infection that provides an excellent basis to study normal and abnormal cell mediated immune responses in the lung. The project will contribute new basic knowledge about the role of IL-16 in immunity, and it will provide additional understanding of protective immunity against the important AIDS co-pathogen C. neoformans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE FUNCTIONS OF ACCESSORY CELLS IN THE LUNG Principal Investigator & Institution: Schneeberger, Eveline E.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-JUL-1986; Project End 06-JUL-2003 Summary: In this proposal we address two central questions in lung dendritic cell (DC) biology. 1. What are the mechanisms by which DC precursors enter the lung to adopt their sentinel function? 2. What role is played by DC in granulomatous inflammation? These questions build on the following two observations made recently in our laboratory. a. DC precursors, and not their mature counterparts, enter the lung in response to chemokines using mechanisms that depend, in part, on CD18 integrin and ICAM-1 expression. b. DC are the first cells to contact intravenously injected antigencoated beads, thereby initiating granuloma formation. Origin of DC precursors. i. We establish the phenotype and function of DC precursors that migrate to the lung and provide evidence that they are a subset of monocytes. ii. Differences in the sensitivity of a. monocytes, b. interstitial lung DC precursors and c. mature lung DC to a series of chemotactic agents is examined in vitro. Parallel studies in vivo examine how the tisssue distribution of these cells is altered when a chemotactic agent is administered intratracheally. iii. By using mutant mice treated with blocking antibodies, we will show for the first time that DC precursor transmigration is dependent on integrins and immunoglobulin superfamily adhesion molecules. Transmigration in situ is examined at steady state, under conditions of heightened migration and after generating increased numbers of circulating DC precursors treatment with flt3 ligand. DC activity in granulomatous inflammation. Using beads coated with mycobacterial antigen, we

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induce granulomas in the lung and examine over time the phenotype and antigen presenting activity of the DC population in the granuloma, hilar lymph nodes and the spleen. The key role of IL-12 in the induction of the cellular immune response in granulomatous inflammation will be demonstrated by i. Immuno-localizing IL-12 in DC. ii. Quantifying IL-12 mRNA by RT-PCR-ELISA and iii. Assaying by ELISA for IL-12 cytokine secretion by DC within the first 12 h after bead inoculation. These studies contribute important new insights into the biology of pulmonary DC, their role in the immune defense of the lung and provide basic information that can be drawn upon to devise strategies to harness these cells in the defense against inhaled pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOREGULATION OF INTESTINAL GRANULOMAS Principal Investigator & Institution: Weinstock, Joel V.; Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 19-APR-1986; Project End 30-NOV-2003 Summary: Our goal is to treat ineffective immune responses like Crohn's disease (CD) by pharmacological manipulation of endogenous immunoregulatory pathways. In CD, defective immunoregulatory circuits probably allow granulomatous inflammation, which leads to tissue damage and fibrosis. Neurokines like substance P (SP) can modulate immune function. Our hypothesis is that SP has a critical role in inflammation at mucosal surfaces and elsewhere, and that immune mechanisms govern SP receptor expression on leukocytes. Using murine schistosomiasis, a chronic granulomatous disease of the liver and intestines, we discovered a SP/SOM IFN-gamma immunoregulatory circuit. We will investigate further this important discovery with the following three specific aims: 1. The first specific aim derives from studies suggesting that SP receptors (SPr) are inducible on inflammatory cells, which could be an important mechanism allowing regulation of neurokine action. We will learn the full extent of SPr distribution among the various granuloma and mucosal immune cell subtypes. Also, we will resolve if antigenic stimulation and cytokines induce or modulate SPr expression. These studies will use a SPr receptor gene, quantitative mRNA analysis and competitive binding assays. 2. It remains unknown if SP is critically important for immune defense. Our second specific aim will use a SPr transgenic mouse to ascertain if normal immune responses need SP. Also, we will analyze the mechanisms leading to the immune disturbances. 3. SP controls IFN-gamma secretion, and IFN-gamma is centrally important to TH1-type immunity. We need to learn how SP regulations IFN-gamma within granulomas and the mucosa, since CD probably results from an inappropriately vigorous Th1 reaction to luminal factors. Thus, the third specific aim is to determine if SP modulates IL-12 production or if SP acts directly on lymphocytes to stimulate IFNgamma secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LEUKOCYTE TRAFFICKING IN SIV INFECTED RHESUS MONKEYS Principal Investigator & Institution: Sasseville, Vito G.; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: In terminal SIV infection in macaques, lentivirus-infected leukocytes are numerous in SIV-specific infiltrates yet are rarely detected at inflammatory sites associated with opportunistic infections such as mycobacteriosis, SV40, and toxoplasmosis or in complete Freund's adjuvant (CFA)-induced skin granulomas This

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refutes the theory that opportunistic infections during HIV/SIV infection serve as a stimulus for the recruitment of lentivirus-infected cells However, during acute SIVinfection we have observed occasional animals with SIV-positive leukocytes associated with Pneumonyssus- and CFA-induced granulomas We have also described viruspositive cells in the cellular infiltrates associated with pulmonary granulomas induced by tetrathyridia of Mesocestoides in a pigtailed macaque (Macaca nemestrina) during acute SIV infection Our hypothesis is that SIV-infected leukocytes are able to traffic to inflammatory sites early in infection, but lose this ability late in dise ase Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LOCAL ANGIOTENSIN SYSTEM IN LUNG FIBROGENESIS Principal Investigator & Institution: Maier, Lisa A.; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2002; Project Start 04-SEP-1998; Project End 31-AUG-2003 Summary: (Adapted from applicant's abstract) Chronic beryllium disease (CBD) is a granulomatous lung disease that occurs after exposure to beryllium in the workplace. Beryllium stimulates an exuberant cellular immune response resulting in granuloma formation which eventually may progress to pulmonary fibrosis. The mechanism of fibrosis in the setting of T-cell mediated hypersensitivity is not well understood. Preliminary studies in CBD have found mast cells as the source of basic fibroblast growth factor (bFGF) in the formation of the fibrosis that surrounds granulomas. It is a potent activator of fibroblast and smooth muscle cell proliferation, contributing to fibrogenesis. Basic FGF is one of the key growth factors stimulated by angiotensin II. Angiotensin-converting enzyme (ACE) and its enzymatic product angiotensin II (ATII) promote fibrosis in cardiovascular disease, by an unknown mechanism. ACE activity is high in CBD. Thus, the investigators hypothesize that the local angiotensin system responds to beryllium-induced lung injury by promoting fibrosis through the production of bFGF. Furthermore, they hypothesize that this fibrotic response is counterbalanced by a cell mediated immune response to beryllium in which there is marked interferon gamma (IFN-y) production. They will conduct experiments to determine whether beryllium can increase ACE activity and ATII production in CBD bronchoalveolar lavage (BAL) cells. By examining biopsy tissues after beryllium skin patch testing, they will assess the role of beryllium in stimulating ACE, ATII, and mRNA expression for ACE and ATII receptors during granuloma formation. The investigators will link the ATII production from beryllium stimulated macrophages to fibrosis by measuring ATII stimulation of the fibrotic growth factor, bFGF, from mast cells using a human mast cell line. They will define the mechanism of bFGF upregulation by ATII. Finally, to demonstrate that the beryllium-mediated immune response inhibits this fibrotic response, they will assess the role of IFN-y in downregulating the ATII stimulated bFGF production. These studies will help establish a role for the angiotensin system in granulomatous lung disease and the path to fibrogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF CELL GROWTH ARREST IN LATENT TUBERCULOSIS. Principal Investigator & Institution: Fontan, Patricia A.; Public Health Research Institute 225 Warren St Newark, Nj 071033535 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009

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Summary: (provided by applicant): During the latent phase of tuberculosis the tubercle bacillus is believed to be metabolically active but in a slow or non-growing state which can resume bacterial replication at an opportune time later in life. However the mechanisms involved in the cessation of Mycobacterium tuberculosis (Mtb) division are unknown. There have been recent descriptions of bacterial possessing systems, resembling plasmid encoded toxin-antitoxin proteins that induce cell growth arrest when the microorganism is exposed to an environmental stress. We and other investigators have identified proteins resembling these putative toxin-antitoxin modules in Mtb. To provide evidence that these systems are cell growth arrest modules involved in the persistent phase of Mtb infection, we propose: 1-To demonstrate the inhibitory effect of the putative Mtb "toxin-antitoxin modules" on bacterial growth in vitro. 2-To determine the patterns of expression of the putative Mtb "toxin-antitoxin modules" during the persistent phase of bacterial infection in mice lung and guinea pig granulomas. 3-To analyze the regulatory mechanisms for the expression of the putative Mtb "toxin-antitoxin modules". 4-To determine the mechanism of action of the putative Mtb '_toxin-antitoxin modules". 5-To evaluate the role of the Mtb "toxin-antitoxin modules" in bacterial virulence, using a model of mouse lung infection. These studies will provide insight into the latent phase of tuberculosis and they will allow us to identify possible targets form the design of antimycobacterial drugs. During the research supported by this proposal the candidate will gain knowledge in the study of transcriptional regulation of Mtb under the mentorship of Dr. Issar Smith, who is an expert in the field. The candidate will obtain expertise in the management of State-ofthe-Art techniques at the Public Health Research Institute, an Institution with a high level of scientific achievement in the area of infectious diseases like TB. The completion of this proposal in this framework of scientific and institutional support will be fundamental for the candidate to establish herself as an independent investigator in the field of Mtb pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METALLOPROTEINASE GRANULOMAS

FUNCTON

IN

TUBERCULOSIS

Principal Investigator & Institution: Izzo, Angelo A.; Microbiol, Immunology & Path (Mip); Colorado State University-Fort Collins Fort Collins, Co 80523 Timing: Fiscal Year 2004; Project Start 01-JUN-2004; Project End 31-MAY-2005 Summary: (provided by applicant): Mycobacterium tuberculosis (Mtb) infects approximately one third of the world's population. In the US, there are an estimated 10 to 15 million people infected with Mtb who have the potential to develop active disease. Among otherwise healthy persons, infection with Mtb is likely to be asymptomatic. In recent years it has become clear that if these individuals become immunosuppressed, as in cases of HIV infection, Mtb infection is reactivated. The purpose of this proposal is to use a murine model of pulmonary Mtb infection to dissect the host's immune response to identify factors that promote the formation and maintenance of granulomas during chronic Mtb infection and possible mechanisms that may also cause reactivation. Expression of anti-mycobacterial immunity depends on type 1 immune cytokines such as interferon-gamma that enable the host to mount a granulomatous inflammatory response to the infection. The lung provides an excellent environment for the organism to persist, despite the presence of a continuous immune response. Matrix metalloproteinases (MMPs) are endopeptidases that degrade the extracellular matrix and have been associated with various pathogenic states. Tissue inhibitors of MMPs regulate the activity of MMPs and provide a mechanism for controlling their activity.

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We propose that during pulmonary Mtb infection, MMPs are a dual-edged sword, being induced by Mtb, but required by the host to form the granuloma and then down regulated to maintain the structure. Specifically, increased MMP activity causes extracellular matrix degradation/tissue remodeling, which enables Mtb to disseminate and facilitates leukocyte trafficking into infected lungs, providing the foundation for granuloma formation. Finally, MMP down regulation is critical for fibrosis formation that is essential for granuloma stability. The MMPs that function during this process are macrophage-derived MMP-2, MMP-9 and MMP-12, which play significant roles in the disease process, being regulated directly by the virulent organism. Understanding how the immune response modulates MMP activity and produces tight, well-formed granulomas will provide insight into mechanisms that could accelerate and stabilize the natural healing process. It is intended that the information obtained from these investigations will provide a better understanding of the immunopathogenesis of tuberculosis and therefore allow for the development of better treatment regimens particularly during reactivation of infection that can be used in association with conventional anti-tuberculosis therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GRANULOMAS

ANALYSIS

OF

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SARCOIDOSIS

Principal Investigator & Institution: Drake, Wonder P.; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2004; Project Start 09-JUL-2004; Project End 30-JUN-2006 Summary: (provided by applicant): Sarcoidosis is a multisystem granulomatous disease of unknown etiology that has worldwide prevalence. In the United States, it most commonly affects African Americans who are less than 40 years of age. The pathologic, epidemiologic, and immunologic features of sarcoidosis are similar to Mycobacterium infections, particularly tuberculosis. In preliminary studies, polymerase chain reaction (PCR) analysis revealed sequences corresponding to Mycobacterium species in 15 of 25 paraffin-embedded granulomas from sarcoidosis patients local to Nashville, TN, but none of 25 control specimens from the same locale (p<0.00002, chi square). This analysis was expanded to include frozen specimens from other regions of the United States, in which mycobacterial nucleic acid was amplified from 50% of frozen sarcoidosis specimens and none of control tissues (p<0.016, Fisher's exact test). These findings lead to the hypothesis that sarcoidosis is an immunologic response in a genetically susceptible host to mycobacterial infection, involving a novel Mycobacterium which is closely related to Mycobacterium tuberculosis. The proposed research will test this hypothesis by (i) evaluating sarcoidosis specimens for the presence of immunodominant genes associated with virulence in mycobacterial infections, and (ii) comparing antigen specific T-cell responses in sarcoidosis patients with normal healthy controls, and patients with M. tuberculosis infection. This work will contribute important new information about the etiology of sarcoidosis and establish a strong experimental framework for ongoing studies of the immunopathogenesis of this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MONOCYTE RECRUITMENT IN PLEUROPULMONARY TB IN AIDS Principal Investigator & Institution: Antony, Veena B.; Professor; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167

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Timing: Fiscal Year 2002; Project Start 01-FEB-1996; Project End 31-JAN-2006 Summary: Tuberculosis is endemic among patients with AIDS and follows an aggressive course with poor localization of mycobacteria into granuloma and widespread infection. Granulomas are monocyte rich collections of cells which derive from the circulating peripheral blood monocyte (PBMC). Monocytes are recruited to the site of tuberculous infection by the interaction of C-C chemokines, (mainly monocyte chemoattractant protein-1, MCP- 1) and monocyte expression of the CCR2 receptor. It is the hypothesis of this proposal that recruitment and retention of the monocyte at the site of tuberculous infection is predicated not only on local release of MCP-1 but on the expression of CCR2 receptor on PBMC. CD4 depletion alters monocyte recruitment and retention by altering the in vivo expression of CCR2 on PBMC and macrophages. This inhibitory effect of CD4 depletion is due to the relative imbalance between Thi and Th2 cytokines. We have developed a model of pleural tuberculosis in CD4 -1- and CD4 +/+ mice to evaluate the Th1/Th2 regulation of the CCR2 receptor on PBMC. We will evaluate our hypothesis in our model of pleural tuberculosis in vivo as well as in vitro in PBMC and elicited pleural macrophages (PM). Our specific aims are 1) To determine the in vivo moncyte influx, granulonia formation, mycobacterial clearance and mortality utilizing our model of pleural tuberculosis in a CD4 knockout mouse model, CD4 -/mice and control, wild type CD4 +1+/- mice. 2) To determine the in vivo effect of CD4 depletion on the compartmentalized and peripheral expression of CCR2 receptor on PBMC and PM and the regulatory role of Th1 (IL2, IL-12) and Th2 (11-10, JL-4) cytokines inCD4 -/- and CD 4 +/+ mice with pleural tuberculosis. 3) To determine the in vitro molecular and cellular regulation of CCR2 expression in PBMC and PM in the presence of Th1 and Th2 cytokines and 4) To determine the role of tubercie bacilli stimulated pleural mesothelial cell derived cytokines in the regulation of CCR2 receoptor on peripheral blood monocytes (PBMC) and pleural niacrophages (PM) in vivo and in vitro. Understanding the mechanism of regulation of CCR2 receptor by Th1 and Th2 cytokines may help us discern the pathophysiology of pleuro-pulmonary tuberculosis seen in patients with AIDS and may help develop therapeutic modalities that augment host-defense responses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NEUROPEPTIDES NEUROCYSTICERCOSIS

IN

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PATHOGENESIS

OF

Principal Investigator & Institution: Robinson, Prema; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Neurocysticercosis (NCC) is a parasitic infection of the human central nervous system caused by the helminth Taenia solium. NCC is recognized as a leading cause of seizures worldwide. Seizures in NCC are evoked by localized granulomatous responses to dying parasites in the brain. The mediators of the seizures are unknown, identification of seizure mediator(s) in NCC may result in treatment with specific antagonists. The neuropeptide substance P (SP) stimulates granuloma growth and Th1 cytokine production. Another neuropeptide, somatostatin, stimulates Th2 cytokine production and impairs granuloma formation. SP evokes epileptiform responses in neurons, whereas, somatostatin has anticonvulsant properties. We divided granulomas associated with murine cysticercosis into 4 stages based on the histologic appearance of the degenerating parasite. Early stage granulomas expressed Th1 cytokines and SP, whereas Th2 cytokines and somatostatin were only expressed in later stages. Preliminary results also noted that behavioral seizures and increased

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hippocampal activity were induced when extracts from early granulomas were injected into brain of rats. Pretreatment with SP receptor antagonist inhibited these effects. Similarly, injection of SP into rat brain also induced seizures and altered hippocampal activity that was completely blocked by pretreatment with SP receptor antagonist or somatostatin. We hypothesize that SP mediates and somatostatin inhibits the granulomatous response and seizures in NCC. Specific aim 1: To test the hypothesis that SP and somatostatin modulate granulomatous responses in cysticercosis. Granuloma size, Th1/Th2 and pro-inflammatory cytokine levels in infected, wildtype mice, SP knockout mice (SP KO), SP receptor KO mice and somatostatin KO mice will be compared. Specific aim 2: To determine if SP and somatostatin are respectively responsible for the mediation and modulation of seizure responses in NCC. SP protein expression will be examined in brain biopsies from NCC patients with seizures. Epileptogenic activity of granuloma extracts from infected, SP KO and somatostatin KO mice will be compared to that from wildtype mice. Specific aim 3: To determine if seizures in NCC are directly due to SP and/or indirectly due to SP induced cytokines. Epileptogenic activity of early granuloma extracts will be tested with or without inhibition or blocking of SP, IL-1beta, TNF-alpha or IL-6. Also epileptogenic activity of early granulomas from infected IL-1beta, TNF-alpha or IL-6 knockouts will be tested. Specific aim 4: To test the hypothesis that somatostatin inhibits seizures in NCC. Epileptogenic activity of early granuloma extracts with or without somatostatin analogues or SOM antagonist will be studied. These studies will determine the importance of SP and SOM in pathogenesis of NCC, and may lead to future use of SP antagonist and SOM analogues as anti-epileptic agents for treatment of seizures in NCC and other seizure related diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENIC T CELLS IN BERYLLIUM-INDUCED LUNG DISEASE Principal Investigator & Institution: Fontenot, Andrew P.; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-JUN-2003 Summary: Chronic beryllium disease (CBD) is a granulomatous disorder which occurs in one to five percent of individuals exposed to beryllium usually in the workplace. The lung is the predominant organ affected, with noncaseating granulomas and the accumulation of CD4+ T cells. Bronchoalveolar lavage (BAL) fluid from CBD patients demonstrates CD4+ T cells which have been selectively activated and have the ability to proliferate in response to beryllium sulfate (BeSO4) in culture. Studies from our laboratory have found alterations in the T cell receptor (TCR) gene expression in the BAL compared to blood of CBD patients. In particular, five CBD patients demonstrated CD4+ T cell expansions expressing Vbeta3. Sequencing the TCR beta-chain (TCRB) and alpha-chain (TCRA) junctional regions expressed in BAL CD4+ T cells demonstrated clonal T cell expansions. Clones from different patients were found to express nearly identical TCRs. We hypothesize that these expanded CD4+ T cell clones are responding to beryllium-peptide complexes in the lungs of patients and are important in the pathogenesis of disease. Studies are proposed to confirm that these T cell clones are selectively expanded in CBD patients and therefore not present in the lungs of healthy control subjects or patients with other granulomatous disorders. We will also study BAL in CBD patients at subsequent times of disease progression for the continued presence of these T cell clones. Using patch testing to BeSO4 in these same patients, we will determine whether similar TCRs are used by CD4+ cells infiltrating the skin. The TCR of in vivo clonal expansions will also be compared to TCR expressed by BAL and blood T

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cells after stimulation with BeSO4 in vitro. Separate studies will focus on the mechanism in which beryllium-reactive CD4+ T cells in CBD patients recognize antigen resulting in stimulation. CD4+ T cell hybridomas expressing the TCR of particular T cell clonal expansions in CBD patients will be used to analyze the response to BeSO4 and determine whether responses are restricted by particular self class II major histocompatibility complex (MHC) molecules. Additional studies will examine whether antigen processing is required for stimulation of these T cell hybridomas. Together, these studies will provide new insight into the immunopathogenesis of CBD and other granulomatous disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT INVESTIGATION OF SAFETY AND EFFICACY OF THALIDOMIDE IN SARCOIDOSIS Principal Investigator & Institution: Oliver, Stephen J.; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002 Summary: Sarcoidosis is a multisystem disease of unknown etiology characterized by the formation of noncaseating granulomas. Disease involvement can be self limited or chronic, ranging from asymptomatic to end organ failure. The disease may affect lungs, thoracic lymph nodes, skin, eyes, and other organs. Corticosteroids remain the primary sarcoidosis therapy. However, steroid treatment has multiple side effects and may fail to alter the disease course. The proinflammatory cytokine TNF-alpha may play an important role in mediating sarcoid disease activity. TNF-alpha production by activated macrophages is an important element in the cell mediated immune response leading to granuloma formation. Serum levels of TNF-alpha and soluble TNF-alpha receptors are elevated in sarcoidosis patients and correlate with disease activity. Thalidomide, an inhibitor of TNF-alpha production, has been shown to have both anti-inflammatory and immune modulating effects in a number of autoimmune diseases, including discoid lupus, aphthous ulcer formation, erythema nodosum leprosum, and others. The addition of thalidomide to antibiotic regimens has also improved morbidity and mortality in animal models of M. tuberculosis infection of the pulmonary and central nervous systems. This study will evaluate the effect of daily thalidomide administration in sarcoidosis patients over a 4 month period, using clinical and laboratory based disease activity measures. Serially recorded clinical disease activity measures include spirometry, skin photographs, erythrocyte sedimentation rates, Health Assessment Questionnaires, and joint counts. Chest x-rays and several skin biopsies will be performed at several defined time points. Laboratory based disease activity measures include plasma TNF-alpha and soluble TNF-alpha receptor, soluble interleukin 2 receptor, and intercellular cell adhesion molecule-1. Interferon gamma plasma levels will also be determined. T-lymphocytes subsets and antigen-stimulated lymphocyte proliferation will be measured. Drug safety in this patient group will be monitored by blood chemistries and cell counts, history and physical exams, and renal function assessments performed during monthly patient visits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PPARGAMMA DYSFUNCTION IN SARCOIDOIS Principal Investigator & Institution: Thomassen, Mary J.; Medicine; Cleveland Clinic Lerner Col/Med-Cwru Cleveland, Oh 44195 Timing: Fiscal Year 2004; Project Start 09-JUL-2004; Project End 30-JUN-2006

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Summary: (provided by applicant): Sarcoidosis is a relatively common inflammatory disease of unknown etiology and significant morbidity. Sarcoid inflammation is characterized by complex interrelationships among macrophages, T-helper lymphocytes, and cytokines (tumor necrosis factor [TNF], interferon gamma [IFNgamma] and others) which lead to formation of granulomas and variable degrees of fibrosis in the lung and other organs. Epidemiologic data (i.e. familial clustering, racial variation) strongly support a genetic role for host susceptibility (i.e. polymorphisms of regulatory genes). A potential regulator of inflammation is the nuclear transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma). This recently described, ligand-dependent transcription factor is expressed in cells of the monocyte-macrophage lineage which play a critical role in sarcoid inflammation. In experimental models of autoimmune and inflammatory diseases, PPARgamma activation antagonizes expression and actions of inflammatory mediators, many of which are known to be overexpressed in sarcoidosis. Preliminary studies indicate that PPARgamma activity and gene expression are deficient in the alveolar compartment of sarcoidosis while in contrast, activity of the inflammatory transcription factor, NF-KappaB is upregulated. Insufficient PPARgamma activity may perpetuate the chronic inflammatory injury of sarcoidosis by failing to repress NFKappaB. Based on these observations, it is hypothesized that PPARgamma regulation is dysfunctional in sarcoidosis. The specific aims of this study are to: (1) Evaluate intrinsic PPARgamma mRNA (by real time RT-PCR) and protein expression (by immunoblotting and immunocytochemistry) in pulmonary granuloma tissue and bronchoalveolar lavage (BAL) cells; (2) Investigate in vitro PPARgamma responses of BAL and peripheral blood cells to challenge with positive (interleukin 4 [IL-4], granulocyte-macrophage colony stimulating factor [GM-CSF]), phorbol myristate acetate [PMA]); and negative (PPARgamma ligands, IFNgamma) regulators of PPARgamma; and (3) Determine by sequence analysis whether PPARgamma polymorphisms are associated with sarcoidosis. The study will use a combination of banked open-lung biopsy specimens as well as bronchoscopically obtained fresh specimens from sarcoidosis patients vs healthy controls to characterize the status of PPARgamma in sarcoidosis. These studies are the first to focus upon the role of PPARgamma in sarcoidosis and preliminary data strongly suggest the presence of PPARgamma dysfunction. Investigation of PPARgamma involvement in sarcoidosis will be critical to better understanding the disease process and to generating novel approaches to therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REACTIVATION TUBERCULOSIS IN A/J MICE Principal Investigator & Institution: Jagannath, Chinnaswamy; Associate Professor; Pathology and Lab Medicine; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant) One quarter of the world's population is infected with M. tuberculosis resulting in approximately 2.9 million deaths each year. Reactivation tuberculosis is the major cause of adult tuberculosis today although the mechanisms that predispose to reactivation are complex and enigmatic. Since animal models are useful for understanding pathogenesis of tuberculosis, we performed a series of studies to standardize murine models of acute, chronic and reactivation tuberculosis by varying the mouse strain, route and dose of infection. We then found that A/J mice were highly susceptible while C57Bl/6 mice were relatively resistant to progressive disease when infected either i.v. or via aerosol routes. A/J mice were unable

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to form granulomas in lungs and their macrophages were defective in killing MTB. Unlike C57Bl/6 mice, A/J mice also underwent an early and near uniform reactivation of tuberculosis following the Cornell model. A/J mice have a deletion in the gene encoding for Complement C5 which in intact mice yields the C5a anaphylatoxin, a known regulator of cytokine and chemokine synthesis of macrophages. Therefore, in this investigation, we will examine the hypothesis that the lack of C5a compromises the immune responses in mice allowing the reactivation of tuberculosis through the following aims. Specific Aim I will investigate whether the deletion in C5 gene affects the synthesis of cytokines (TNF alpha, IL1-beta and IL-6), prevents macrophage activation and thereby macrophage mediated killing of MTB in A/J mice. Specific Aim II will investigate the effects of the deletion in C5 gene to the secretion of chemokines by MTB infected A/J macrophages and evaluate whether they are important in causing influx of immune cells into the lungs and formation of granulomas. Specific Aim III will characterize histological, cytokine and chemokine responses of lungs in A/J mice to determine the type of immune response (Th1 vs Th2) that dominates during the reactivation of tuberculosis. These studies are anticipated to enhance our understanding on putative mechanisms that precede the reactivation of tuberculosis in the lungs of mice and ultimately help us to develop better strategies to prevent tuberculosis in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF INFLAMMATION BY SOMATOSTATIN VIA SSTR 2 Principal Investigator & Institution: Elliott, David E.; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Somatostatin (SOM) decreases inflammation in murine models and human disease. SOM is a cyclic 14 amino acid peptide produced in the mucosa and at sites of inflammation. SOM is made by inflammatory macrophages. SOM may have a critical role regulating inflammation by inhibiting T cell IFN-? release. Macrophage SOM production is induced by LPS, IFN-?, IL 10, TNF-?, PgE2 and cAMP. Murine inflammatory T cells express only one type of SOM receptor, SSTR2. SSTR2 also is expressed at sites of inflammation in patients. SOM-mediated inhibition of IFN-? production requires functional SSTR2. The central hypothesis of this proposal is that the regulation of SOM production and signaling through the SSTIR2 receptor controls Th1 responses in health and disease. SOM may be a particularly important immunomodulator at mucosal surfaces where SOM is plentiful. This proposal has three specific aims. Aim 1 seeks to determine how macrophage production of SOM is regulated at the molecular level. The goal of this aim is to elucidate the pathways used by LPS and IFN-? to induce macrophage SOM expression. Aim 2 seeks to determine how SSTR2 regulates T cell function. This aim will determine if SSTR2 couples to phosphatases and inhibitory signaling factors in Th1 cells to down regulate IFN-? release. Aim 3 seek to determine the in vivo effects of removing SOM-SSTR2 circuitry on inflammation. This aim will use inbred mice that lack SOM or SSTR2 to study the immunoregulatory role of SOM-SSTR2 in three murine models of inflammation. The models are: TNBS colitis, IL 10 deficient colitis, and schistosome egg granulomas.This proposal will study the mechanisms controlling SOM production and regulation of T cell-mediated inflammation. These studies will provide novel insights into the immunoregulation of inflammation at mucosal surfaces rich in endogenous SOM. The results of these studies will provide rationale for novel therapeutic treatment of IBD and other inflammatory diseases.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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 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

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Project Title: ROLE OF FAS LIGAND IN THE PATHOGENESIS OF LUNG GRANULOMA Principal Investigator & Institution: Serlin, David M.; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 12-FEB-2003 Summary: (provided by applicant): Granulomatous inflammation represents a complex and tightly regulated response to multiple types of antigens. Cell-antigen, as well as cellcell, interactions determine the fate of the granulomatous response: involution or tissue destruction. Although Fas ligand (FasL)-mediated apoptosis, or programmed cell death, has previously been shown important in both human and animal inflammation, its potential role in regulating granuloma development is yet to be defined. Using a murine model of pulmonary granuloma formation, we have demonstrated that FasL is expressed and apoptosis is active in lung granuloma. Preliminary data also suggest that FasL-deficient animals develop an aberrant granulomatous response. We hypothesize that Fas and FasL-mediated signals are essential to the resolution of the pulmonary granulomatous response. Using standard techniques and a well-characterized model of Schistosoma (S.) mansoni egg-induced synchronous lung granulomas, we propose to first characterize the expression of Fas and FasL and the degree of apoptosis during

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granuloma development. Second, using FasL-deficient (gld) mice, we will determine the impact of defective Fas/FasL signaling on granuloma formation, cytokine production and resolution. As a result, we will show that the Fas/FasL signaling pathway plays an integral role in down-modulating the granulomatous inflammatory process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF OSTEOPONTIN IN GRANULOMATOUS INFLAMMATION Principal Investigator & Institution: Berman, Jeffrey S.; Professor of Medicine; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: The key regulatory events behind granuloma formation and particularly the role of the granuloma matrix are not well understood. We have recently demonstrated the presence of the early T-cell activation gene Eta-1 (also known as osteopontin {OPN}, a bone matrix acidic glycoprotein) in active granulomatous lesions of tuberculosis rid sarcoidosis. Our preliminary data demonstrate that Eta-1/OPN is a potent chemoattractant, adhesin and proliferative co-stimulant for T lymphocytes in vitro. These data, the association of reduced osteopontin in mice with defective host response to intracellular pathogens such as Rickettsia tsutsugamushi in vivo, and the fact that steopontin is a potent chemoattractant for monocytes and macrophages suggest that Eta-1/OPN represents a new class of RGD-containing cytokine which regulates T cell and macrophage function, serving a key role in the initiation and maintenance of (lung) granulomatous inflammation. Specifically, we hypothesize that the expression of Eta1/OPN by macrophages, lymphocytes, endothelial and epithelial cells is an early and important event in granuloma formation which regulates inflammatory cell traffic, cellular activation and cytokine production, proliferation, and cell death. This grant proposes to elucidate its immunologic functions and study its role in granuloma formation. In vitro studies include characterizing the production of Eta-1/OPN by immune cells and lung cells and the phosphorylation and glycosylation variants produced by these cells. The effects on T cell function of purified and recombinant OPN will be studied. In vivo studies will be performed to determine the role of Eta-1/OPN in the formation of granulomas in he lung. A model will be used in which granulomas are induced by the embolization of sepharose beads containing antigens which induce the formation of granulomas dependent on Th1 and Th2 cytokines. The model will be applied to a genetically engineered Eta-1/OPN deficient mouse and wild type controls. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF OXIDATVE STRESS IN CHRONIC BERYLLIUM DISEASE Principal Investigator & Institution: Day, Brian J.; Associate Professor; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206 Timing: Fiscal Year 2003; Project Start 04-AUG-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The overall goal of this application is to understand the role of oxidative stress in chronic beryllium disease (CBD). CBD is an inflammatory hypersensitivity lung disease that continues to occur in 10% of the estimated 800,000 beryllium-exposed workers in the United Sates and is characterized by the presence of non-caseating granulomas with accumulation of macrophages and beryllium specific CD4+ T lymphocytes. Upon beryllium stimulation in vitro, these T cells proliferate and produce Th1 cytokines (i.e. TNF-alpha, INF-gamma, and IL-2) at unusually high levels. The precise molecular mechanism(s) by which beryllium regulates the production of these high levels of cytokines is unknown. It is hypothesized that oxidative stress

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enhances the APC's ability to present beryllium antigen to T cells, which may, in part, explain both the excessive cytokine response and associated lung granuloma formation. Exciting preliminary studies indicate that the redox status of the antigen presenting cell (APC) affects the T cell's response and may help explain why only a portion of the people exposed to beryllium actually develop CBD. The presence of APCs expressing class II molecules is required for CD4+ T cells from CBD patients to proliferate in the presence of beryllium in vitro. This project will use a modification of the clinical beryllium lymphocyte proliferation test (BeLPT) to examine the effect of redox balance on beryllium antigen presentation. This system will enable the testing of the hypothesis that oxidative stress affects the APC's ability to present beryllium antigen to T cells and the role of oxidative stress in modulating T cell activation. The hypothesis is addressed by the AIMS: (1) examine the effect of beryllium on APC and T cell antioxidant status and stimulation response; (2) examine the effect of altered APC glutathione status on beryllium antigen presentation; (3) examine the effect of altered oxidant status on beryllium antigen presentation by APC and T cell activation. Primary endpoints measured are (1) glutathione and enzymes involved in its synthesis and utilization; (2) markers of lipid, protein and DNA oxidation; and (3) T cell proliferation and Th1 cytokine release and accessory molecule expression. It is proposed that beryllium, itself; initiates oxidative stress in the APC and also serve as the antigen. Inherent differences in either resting APC antioxidant status or APC oxidant response to beryllium are predicted to be critical factors in determining whether people exposed to beryllium go on to develop CBD. These studies have the potential to further define the etiology of CBD, risk factors, and suggest novel approaches to prevent and treat this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE/FUNCTION ANALYSIS OF PHAGOCYTE PROTEINS Principal Investigator & Institution: Dinauer, Mary C.; Professor; Pediatrics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 02-DEC-1991; Project End 30-JUN-2006 Summary: (provided by applicant): The phagocyte respiratory burst oxidase that generates the superoxide radical plays a central role in host defense and the inflammatory response. Assembly of the active oxidase complex requires the participation of both membrane and cytosolic proteins, and is regulated by small GTPases. A phagocyte-specific b-type flavocytochrome heterodimer, located in the plasma and, in neutrophils, specific granule membranes, is the focal point for oxidase assembly, and contains both the flavin and heme redox centers for transfer of electrons from NADPH to molecular oxygen. Genetic defects in oxidase proteins, including the two flavocytochrome subunits, result in chronic granulomatous disease (CGD), a syndrome characterized by an absent respiratory burst, recurrent infections, and chronic granulomas. The structural and functional relationships between the various oxidase subunits and the assembly of the active NADPH oxidase complex remain incompletely understood. This low-potential flavocytochrome is a heterodimer comprised of gp91 phox, a 91-kDa glycoprotein encoded by an X-linked gene that is the site of mutations in X-linked CGD, and p221-phOx, a non-glycosylated peptide derived from an autosomal CGD locus. The proposed studies take a genetic approach to investigating the structure and function of the oxidase flavocytochrome b and its role as a focal point for assembly of the active NADPH oxidase complex. The project has 3 specific objectives, which take advantage of a gp91 phox deficient phagocyte cell line developed by gene targeting as well as heterologous cell systems we have developed for expression of functional

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recombinant oxidase subunits. First, the relative roles of gp91 phox and p22phox in flavocytochrome b biosynthesis and function will be examined using heterologous cells for expression of unassembled subunits, which are otherwise unstable in phagocytes. Second, identification of domains in gp91 phox and p22 phox that function in the assembly and regulation of oxidase activity will pursued, using a strategy that emphasizes site-directed mutagenesis of candidate hydrophilic regions followed by expression and analysis of function in intact cells. Third, functional domains important for flavocytochrome b trafficking and NADPH oxidase assembly during phagocytosis will be investigated using similar approaches in heterologous and phagocytic cell lines. These studies will provide further insight into the superoxide-generating system of the phagocyte, which may lead to new approaches in modulating superoxide formation in the inflammatory response and host defense. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDIES OF M TUBERCULOSIS SURVIVAL IN ANIMAL MODELS Principal Investigator & Institution: Smith, Issar; Member; Public Health Research Institute 225 Warren St Newark, Nj 071033535 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2004 Summary: Tuberculosis, one of the oldest human diseases, still kills approximately 3 million people annually, despite the use of a generally safe, but sometimes ineffectual vaccine. While this staggering number is frightening enough, 1/3 of the world s population has been infected by the causative organism, Mycobacterium tuberculosis. Depending on the immunological state and/or age of the latently infected individual, the disease can reoccur, without new infections, at a significant frequency. Antibiotics can control tuberculosis, when therapy is given quickly and efficiently, but the disease is not cured and quiescent M. tuberculosis can be reactivated. Antibiotic resistance is also a growing problem. Currently, little is known about bacterial survival mechanisms in the lung and the nature of the so-called latent state. The general aims of this new grant proposal are: the identification and characterization of M. tuberculosis genes that are specifically induced late in the infection of animal models. Information concerning these differentially regulated bacterial genes and their products will help us to understand interactions between M. tuberculosis and cells in the lung. This knowledge will aid in the development of new anti-tubercular therapies and will provide bacterial markers that will be useful in evaluating the efficacy of other treatments. An IVET romoter trap system has been previously developed in our laboratory to isolate M. tuberculosis genes that are induced after infection of human macrophages and mice. We will extend the IVET screening method to guinea pigs, because the progression of the disease in lungs of this animal model more closely resemble the human disease than that observed in mouse infections. In addition, we have modified our mouse IVET protocols to identify M. tuberculosis genes that are expressed late in the infectious process. The expression of M. tuberculosis genes in infected lung tissue will also be measured. A sensitive and accurate fluorescence based RT-PCR method has been developed to quantitate the in vivo expression of M. tuberculosis genes. Several genes that are induced during infection of human macrophages have already been identified including several iron regulated genes. We will extend this technique to study bacterial gene expression in guinea pig granulomas and mouse lungs. M. tuberculosis genes identified by the experiments outlined above as being induced late in mouse or guinea pig infection will be tested for their roles in virulence. Using techniques developed in our laboratory and others, we will systematically inactivate these genes and will test the ability of mutants to survive in macrophages and animal models.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: T CELLS IN GRANULOMATOUS IMMUNE RESPONSES Principal Investigator & Institution: Sandor, Matyas; Pathology and Lab Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 31-MAY-2005 Summary: Early immunity to infectious agents generally involves a very well defined T cell response to a few immunodominant epitopes. However, the role of antigen specificity in T cell accumulation at chronic inflammatory sites is much less understood. The primary goal of this application is to understand the role of antigen and T cell receptor specificity in chronic granulomatous inflammatory reactions. This information is not presently available due to the technically challenging problem of tracing the low frequency T cells specific for a given antigen. T cell receptor transgenic animals and their respective antigens will be used to overcome this difficulty. This technology will help us to characterize the phenotype and function of T cells activated specifically by antigen or through alternative activation pathways within a localized inflammatory site. Our model will be one of granulomas induced by Leishmania chagasi donovani (LCD) where T cells are crucial for granuloma formation. T cell receptor transgenic mice with a T cell repertoire consisting only two different monospecific T cells will be infected with recombinant LCD expressing an epitope recognized by only one kind of the T cells. The localization and activation stages of these cells will be measured. The two transgenic T cell populations will be sorted and their capacity to control parasite load, form granulomas, and produce lymphokines will be tested in adoptive transfer studies. The experiments will be repeated in wild type adoptive transfer recipients to examine the function of the monospecific T cells within a normal population. These systems will be used to study the effects of immunization on cytokine and effector functions of specific and non-specific T cells. There are three Specific Aims for our application. First, we will determine the proportion of antigen-specific and unrelated antigen restricted T cells in granulomas and in the immune periphery during infection. (Aim 1). Next, we will study the functional role and characteristics of these defined populations throughout the parasitic infection (Aim 2). Finally, we will use vaccination to modify the T cells, activated specifically by antigen or through alternative activation pathways in the granulomas in order to design new, precisely targeted therapies for T cell functions in parasitic diseases (Aim 3). We believe that the successful completion of this research project will lead to an improved understanding of the role of T cells in granulomatous diseases and thus provide the foundation for new therapeutic methodologies for controlling granulomatous inflammatory diseases, such as leishmaniasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE TUBERCULOSIS

DYNAMICS

OF

GRANULOMA

FORMATION

IN

Principal Investigator & Institution: Kirschner, Denise E.; Associate Professor; Microbiology and Immunology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant) The goal of this proposal is to explain the formation of granuloma in infection with Mycobacterium tuberculosis. Understanding granuloma formation and function will elucidate the primary immune mechanism for controlling tuberculosis infection. Our goal is to simulate the process of granuloma formation on a

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spatio-temporal scale and present the results in a time-lapse movie format. This will yield an interactive tool to study the role of specific immune elements in granuloma formation and function. Development of a virtual model of human infection will allow for integration of the plethora of chemokine, cytokine, cellular influx information and other relevant immunological factors, as generated by experimental systems. To this end, powerful techniques (e.g., microarrays) are available for obtaining comprehensive gene expression data. Using these methods to survey expression within the granulomas of non-human primates and mice will enable us to determine which immunological mediators are involved in granuloma formation, what the timing of their expression is in the formation, and their location within the granuloma. Further studies will indicate which cell-types are expressing which mediators. Our specific aims are to: (1) Identify the temporal and spatial expression of host immune elements participating in granuloma formation using gene expression tools in murine models of tuberculosis (2) Identify the temporal and spatial expression of host immune elements participating in granuloma formation using gene expression tools in murine models of tuberculosis (3) Determine the dynamics of granuloma formation and function in humans using mathematical models of the granuloma response in tuberculosis. Through this unique approach, the interaction of multiple factors that control the formation of the granuloma will be defined. Key parameters governing these interactions will be identified. The ability to synthesize the data generated by the experiments in the models allows for an understanding of the dynamics of granuloma formation as more than the sum of its parts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF MYCOBACTERIA IN CROHN'S DISEASE Principal Investigator & Institution: Graham, David Y.; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2006 Summary: (provided by applicant): Crohn's disease is an idiopathic non- caseating granulomatous disease. One of the proposed etiologies is infection with Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis), the causative agent of Crohn's-like disease in ruminants (Johne's disease). Recent evidences to support M paratuberculosis infection in Crohn's disease include: 1) its isolation from Crohn's disease tissues and breast milk by culture, 2) its identification in tissues by PCR assays, 3) its detection as cell wall deficient forms in tissues by in situ hybridization, 4) the long term remission (possibly cure) in an increasing number of Crohn's patients by using anti-mycobacterial therapies, and 5) by an association with the M paratuberculosis antigens p35, p36 and the 32k mycobacterial associated antigen termed HupB protein. These data suggest a causal role for mycobacteria in at least a proportion of patients with Crohn's disease. Identification of the subgroup of Crohn's disease patients infected with M paratuberculosis has been hampered due to the lack of a simple and specific serodiagnostic test to identify those who would be candidates for anti- mycobacterial therapy. The long-range objective of this proposal is to confirm M paratuberculosis p35/ p36 antigens as serologic markers and to test whether there are specific clinical/pathologic stratification(s) that correlate with their presence. We will assess the presence of M paratuberculosis infection in Crohn's disease patients by serologic testing of sera from patients and controls and in situ hybridization for the detection of the cell wall-deficient form of M paratuberculosis in involved diseased tissues. We will also use the laser capture microdissection technique to test whether M paratuberculosis are present in granulomas of Crohn's disease patients. The results from serology and

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molecular studies will be compared with the clinical/pathological information and demographic and epidemiologic data gathered about each patient as well as with outcome of anti-mycobacterial therapy. The results of this study should either confirm or refute the proposed etiologic association of M. paratuberculosis and Crohn's disease as well as the identification of patients with Crohn's disease and M. paratuberculosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF OSTEOPONTIN IN EARLY GRANULOMA FORMATION Principal Investigator & Institution: O'regan, Anthony; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 12-APR-2000; Project End 31-MAR-2005 Summary: Therapeutic options for granulomatous disease are limited by an incomplete understanding of granuloma pathogenesis. The role of granuloma matrix in granuloma formation is unknown. Early T lymphocyte activation-1/Osteopontin, is an RGD containing matrix protein that is expressed in early cell mediated immune responses and modulates T cell and monocyte function in vitro. As initial granuloma formation is dependent on T cell:monocyte interactions, it is hypothesized that Eta- 1/Opn plays a role in granuloma development by regulating the early recruitment, activation and cytokine production of T cells and monocytes. The work proposed in this grant will characterize the ability of Eta-1/Opn to regulate T cell and monocyte migration, adhesion and cytokine production in vitro. Based on these studies, the in vivo role of Eta-l/Opn will be determined by inducing synchronous pulmonary granulomas in Eta1/Opn deficient (knockout) and Eta-1/Opn over-expressing (lung specific transgenic) mice. The research training plan includes formal course work, bench research and clinical activities and will allow the investigator to gain expertise in a broad range of experimental techniques including basic studies of cellular immunology, molecular biology, histopathology, and animal models of disease. An experienced advisory committee will regularly review the progress of the investigator and the institutional environment is well equipped to facilitate the proposed experiments. The investigator will participate in a broad range of research, clinical and ethics seminars provided by the institution and attend national immunology meetings and symposia relevant to granuloma formation. The goal of the investigator is to acquire conceptual and technical skills in preparation for an independent research career in academic pulmonary immunology. Understanding early determinants and the role of matrix in granuloma development will provide basic insights into granuloma pathogenesis and may contribute to novel therapeutic approaches to granulomatous disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE OF THE GRANULOMA IN M. TUBERCULOSIS INFECTIONS Principal Investigator & Institution: Russell, David G.; Professor and Chairperson; Microbiology and Immunology; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 30-SEP-1995; Project End 31-MAR-2006 Summary: M. tuberculosis demonstrates an extraordinary penetrance of the human population. Much of its success is liked to its ability to persist within the host, which is dependent on the formation of granulomas, or localized infections that support bacterial persistence without overt disease. The granuloma fulfills functions ambivalent to the

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host because although it limits spread of the infection it also provides a haven for the bacterium from the more extreme rigors of the host immune response. Dr. Russell proposes to extend his existing studies into the life cycle stages of M. tuberculosis by studying how both the host and the bacterium initiate and maintain the granuloma in both the murine and human infections. The specific aims of the proposal are: 1. Characterization of the bacterial factors that induce and modulate granuloma development. M. tuberculosis synthesize and release 7 major lipids these lipids induce granuloma-like structures in mice and stimulate a pro-inflammatory response in macrophages in culture. These lipids will be identified structurally and their biological activities delineated. 2. Elucidation of the roles of host cytokines, chemokines and their receptors in the biology of the granuloma. The ability of the cell wall lipids to induce granuloma in non-immune and immune mice will be determined and compared with bacterial granulomas. Bacterial lipid granulomas will be dissected in an in vivo model that mixes labeled macrophages from relevant knock-out mice with the lipid-bearing particles and the data compared to immunohistological analysis of murine tuberculosis granulomas. The PI will also develop an in vitro cell migration model to determine the cytokines and chemokines responsible for recruitment of macrophages to the infection foci. 3. Examination of human alveolar macrophages from BAL cells from tuberculosis patients. These studies will encompass functional characterization of BAL macrophages for phagocytosis, vacuolar acidification and cellular responsiveness. The PI will also examine the cytokine/chemokine profiles of these cells as well as whether or not they contain mycobacterial cell wall constituents. The BAL cells will also be examined in cell migration assays based on the result from the murine granuloma model described in aim # 2. 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 “granulomas” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for granulomas in the PubMed Central database: •

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A chemoattractant cytokine associated with granulomas in tuberculosis and silicosis. by Nau GJ, Guilfoile P, Chupp GL, Berman JS, Kim SJ, Kornfeld H, Young RA.; 1997 Jun 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21064

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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Accessory cell function of liver granuloma macrophages of Schistosoma mansoniinfected mice. by Schook LB, Wellhausen SR, Boros DL, Niederhuber JE.; 1983 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=264381

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Adequate Expression of Protective Immunity in the Absence of Granuloma Formation in Mycobacterium tuberculosis-Infected Mice with a Disruption in the Intracellular Adhesion Molecule 1 Gene. by Johnson CM, Cooper AM, Frank AA, Orme IM.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108103

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Alteration of granuloma angiotensin I-converting enzyme activity by regulatory T lymphocytes in murine schistosomiasis. by Weinstock JV, Boros DL.; 1982 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351063

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Ampicillin concentrations in human dental granuloma after a single oral administration of talampicillin. by Akimoto Y, Nishimura H, Komiya M, Kaneko K, Fujii A, Tamura T.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172221

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Analysis of cells of the mononuclear phagocyte series in experimental mycobacterial granulomas by monoclonal antibodies. by Mathew RC, Katayama I, Gupta SK, Curtis J, Turk JL.; 1983 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=347945

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Analysis of egg granuloma formation in Schistosoma japonicum-infected mice treated with antibodies to interleukin-5 and gamma interferon. by Cheever AW, Xu YH, Sher A, Macedonia JG.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258998

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Angiotensin-1-converting enzyme activity of murine macrophages isolated from granulomas elicited by eggs of Schistosoma mansoni. by Krulewitz AH, Stadecker MJ, Wright JA, Fanburg BL.; 1983 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=264739

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Anti-L3T4 antibody treatment suppresses hepatic granuloma formation and abrogates antigen-induced interleukin-2 production in Schistosoma mansoni infection. by Mathew RC, Boros DL.; 1986 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260243

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Both Interleukin-4 (IL-4) and IL-4 Receptor [alpha] Signaling Contribute to the Development of Hepatic Granulomas with Optimal Antileishmanial Activity. by Stager S, Alexander J, Carter KC, Brombacher F, Kaye PM.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166035

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Brain Granulomas in Neurocysticercosis Patients Are Associated with a Th1 and Th2 Profile. by Restrepo BI, Alvarez JI, Castano JA, Arias LF, Restrepo M, Trujillo J, Colegial CH, Teale JM.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98532

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Cloning of TH0- and TH2-type helper lymphocytes from liver granulomas of Schistosoma mansoni-infected mice. by Zhu Y, Lukacs NW, Boros DL.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186215

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Deficiency of interleukin-2 production upon addition of soluble egg antigen to cultures of isolated hepatic granulomas or hepatic granuloma cells from mice infected with Schistosoma japonicum. by Stavitsky AB, Harold WW.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313452

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Distribution of cefpirome (HR 810) to exudate in the croton oil-induced rat granuloma pouch and its therapeutic effects on experimental infections in the pouch. by Arai S, Kobayashi S, Hayashi S, Sakaguchi T.; 1988 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=175875

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Effect of Antimacrophage Serum on Dermal Tuberculin Sensitivity and Allergic Pulmonary Granuloma Formation in Rabbits. by Moore VL, Myrvik QN.; 1970 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=416095

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Effects of continuously administered murine interleukin-1 alpha: tolerance development and granuloma formation. by Otterness IG, Golden HW, Brissette WH, Seymour PA, Daumy GO.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313520

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Endogenous gamma interferon is essential in granuloma formation induced by glycolipid-containing mycolic acid in mice. by Asano M, Nakane A, Minagawa T.; 1993 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280933

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Eosinophil chemotactic lymphokine produced by egg-associated granulomas in murine schistosomiasis japonicum. by Owhashi M, Maruyama H, Nawa Y.; 1986 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260229

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Epithelioid granuloma induced by muramyl dipeptide in immunologically deficient rats. by Nagao S, Ota F, Emori K, Inoue K, Tanaka A.; 1981 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=350966

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Establishment and characterization of an antigen-specific T-cell line from liver granulomas of Schistosoma mansoni-infected mice. by Ragheb S, Mathew RC, Boros DL.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=259952

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Exudate Levels and Bactericidal Activity of Cefazolin in a New Local Infection System Using Rat Granuloma Pouches. by Nishida M, Murakawa T.; 1977 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=352126

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Fatal Granuloma Necrosis without Exacerbated Mycobacterial Growth in Tumor Necrosis Factor Receptor p55 Gene-Deficient Mice Intravenously Infected with

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Mycobacterium avium. by Ehlers S, Benini J, Kutsch S, Endres R, Rietschel ET, Pfeffer K.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116546 •

Granulocyte-macrophage colony-stimulating factor enhances the production of eosinophil chemotactic lymphokine by egg-associated granulomas of Schistosoma japonicum-infected mice. by Owhashi M, Maruyama H, Nawa Y.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260653

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High-Level Expression of NRAMP1 in Peripheral Blood Cells and Tuberculous Granulomas from Mycobacterium bovis-Infected Bovines. by Estrada-Chavez C, Pereira-Suarez AL, Meraz MA, Arriaga C, Garcia-Carranca A, Sanchez-Rodriguez C, Mancilla R.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100114

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Histiocytosis X. Purified (T6+) cells from bone granuloma produce interleukin 1 and prostaglandin E2 in culture. by Arenzana-Seisdedos F, Barbey S, Virelizier JL, Kornprobst M, Nezelof C.; 1986 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423345

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Identification by 16S rRNA Gene Analyses of a Potential Novel Mycobacterial Species as an Etiological Agent of Canine Leproid Granuloma Syndrome. by Hughes MS, James G, Ball N, Scally M, Malik R, Wigney DI, Martin P, Chen S, Mitchell D, Love DN.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86311

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Identification of larval cross-reactive and egg-specific antigens involved in granuloma formation in murine schistosomiasis mansoni. by Lukacs NW, Boros DL.; 1991 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258158

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Immunohistochemical distribution of ferritin, lactoferrin, and transferrin in granulomas of bovine paratuberculosis. by Momotani E, Furugouri K, Obara Y, Miyata Y, Ishikawa Y, Yoshino T.; 1986 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=261048

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Immunopathogenesis of Pulmonary Granulomas in the Guinea Pig after Infection with Mycobacterium tuberculosis. by Turner OC, Basaraba RJ, Orme IM.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145351

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Immunostimulatory mouse granuloma protein. by Fontan E, Fauve RM, Hevin B, Jusforgues H.; 1983 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=394304

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In Situ Detection of Mycobacterium tuberculosis Transcripts in Human Lung Granulomas Reveals Differential Gene Expression in Necrotic Lesions. by Fenhalls G, Stevens L, Moses L, Bezuidenhout J, Betts JC, Helden PV, Lukey PT, Duncan K.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130373

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In Situ Study of Abundant Expression of Proinflammatory Chemokines and Cytokines in Pulmonary Granulomas That Develop in Cynomolgus Macaques

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Experimentally Infected with Mycobacterium tuberculosis. by Fuller CL, Flynn JL, Reinhart TA.; 2003 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=308896 •

In Vivo Administration of Mycobacterial Cord Factor (Trehalose 6,6[prime prime or minute]-Dimycolate) Can Induce Lung and Liver Granulomas and Thymic Atrophy in Rabbits. by Hamasaki N, Isowa KI, Kamada K, Terano Y, Matsumoto T, Arakawa T, Kobayashi K, Yano I.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97662

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Induced and spontaneous diabetes mellitus and suppression of cell-mediated immunologic responses. Granuloma formation, delayed dermal reactivity and allograft rejection. by Mahmoud AA, Rodman HM, Mandel MA, Warren KS.; 1976 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=436660

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Interactions between adherent mononuclear cells and lymphocytes from granulomas of mice with schistosomiasis mansoni. by Elliott DE, Ragheb S, Wellhausen SR, Boros DL.; 1990 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258679

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Intercellular adhesion molecule 1 is the major adhesion molecule expressed during schistosome granuloma formation. by Ritter DM, McKerrow JH.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174435

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Interleukin 5 is required for the blood and tissue eosinophilia but not granuloma formation induced by infection with Schistosoma mansoni. by Sher A, Coffman RL, Hieny S, Scott P, Cheever AW.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53199

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Isolated hepatic granulomas from mice infected with Schistosoma mansoni contain nerve growth factor. by Varilek GW, Weinstock JV, Pantazis NJ.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=259061

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Markedly elevated angiotensin converting enzyme in lymph nodes containing nonnecrotizing granulomas in sarcoidosis. by Silverstein E, Friedland J, Lyons HA, Gourin A.; 1976 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=430465

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Microbicidal activity and morphological characteristics of lung macrophages in Mycobacterium bovis BCG cell wall-induced lung granuloma in mice. by Kato K, Yamamoto K, Okuyama H, Kimura T.; 1984 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263224

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Modulation of Schistosoma mansoni egg-induced granuloma formation: I-J restriction of T cell-mediated suppression in a chronic parasitic infection. by Green WF, Colley DG.; 1981 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=319965

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Mononuclear Cell Recruitment, Granuloma Assembly, and Response to Treatment in Experimental Visceral Leishmaniasis: Intracellular Adhesion Molecule 1-Dependent and -Independent Regulation. by Murray HW.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97712

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Mycobacterium bovis BCG-Induced Granuloma Formation Depends on Gamma Interferon and CD40 Ligand but Does Not Require CD28. by Hogan LH, Markofski W, Bock A, Barger B, Morrissey JD, Sandor M.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98196

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Mycobacterium tuberculosis Uptake by Recipient Host Macrophages Is Influenced by Environmental Conditions in the Granuloma of the Infectious Individual and Is Associated with Impaired Production of Interleukin-12 and Tumor Necrosis Factor Alpha. by Li YJ, Petrofsky M, Bermudez LE.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130307

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Nasal Granuloma Caused by Scedosporium apiospermum in a Dog. by Cabanes FJ, Roura X, Garcia F, Domingo M, Abarca ML, Pastor J.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105201

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Passive transfer of acquired resistance to Listeria monocytogenes infection is independent of mononuclear cell granuloma formation. by Roberts EC, Demartini JC, Orme IM.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260054

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Pasteurella haemolytica-like bacterium from a progressive granuloma of cattle in Brazil. by Ribeiro GA, Carter GR, Frederiksen W, Riet-Correa F.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267570

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Protective immunity and granuloma formation are mediated by two distinct tumor necrosis factor alpha- and gamma interferon-dependent T cell-phagocyte interactions in murine listeriosis: dissociation on the basis of phagocyte adhesion mechanisms. by Mielke ME, Rosen H, Brocke S, Peters C, Hahn H.; 1992 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=257088

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Recombinant interleukin-1 alpha augments granuloma formation and cytokine production but not parasite clearance in mice infected with Leishmania donovani. by Curry AJ, Kaye PM.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=257483

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Regulation of Mycobacterium bovis BCG and foreign body granulomas in mice by the Bcg gene. by Sato IY, Kobayashi K, Kasama T, Kaga S, Kasahara K, Kanemitsu H, Nakatani K, Takahashi T, Nakamura RM, Skamene E, et al.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258611

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Regulation of schistosome egg granuloma formation: host-soluble L-selectin enters tissue-trapped eggs and binds to carbohydrate antigens on surface membranes of miracidia. by El Ridi R, Velupillai P, Harn DA.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174434

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Relationship of BCG-Induced Pulmonary Delayed Hypersensitivity to Accelerated Granuloma Formation in Rabbit Lungs: Effect of Cortisone Acetate. by Moore VL, Myrvik QN.; 1973 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=422758

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Role of Cord Factor (Trehalose-6, 6[prime prime or minute]-Dimycolate) in Allergic Granuloma Formation in Rabbits. by Moore VL, Myrvik QN, Kato M.; 1972 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=422481

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Role of lipoxygenase products in murine pulmonary granuloma formation. by Kunkel SL, Chensue SW, Mouton C, Higashi GI.; 1984 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370504

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Role of the major histocompatibility complex in resistance and granuloma formation in response to Mycobacterium lepraemurium infection. by Adu HO, Curtis J, Turk JL.; 1983 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=264915

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Role of the thymus in streptococcal cell wall-induced arthritis and hepatic granuloma formation. Comparative studies of pathology and cell wall distribution in athymic and euthymic rats. by Allen JB, Malone DG, Wahl SM, Calandra GB, Wilder RL.; 1985 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423980

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Role of thymus for N-acetyl muramyl-L-alanyl-D-isoglutamine-induced polyarthritis and granuloma formation in euthymic and athymic nude rats or in neonatally thymectomized rats. by Kohashi O, Pearson CM, Tamaoki N, Tanaka A, Shimamura K, Ozawa A, Kotani S, Saito M, Hioki K.; 1981 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351375

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Schistosoma mansoni egg granuloma size reduction in challenged baboons after vaccination with irradiated cryopreserved schistosomula. by Damian RT, Roberts ML, Powell MR, Clark JD, Lewis FA, Stirewalt MA.; 1984 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=345547

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Sequential Expression of the Neuropeptides Substance P and Somatostatin in Granulomas Associated with Murine Cysticercosis. by Robinson P, White AC, Lewis DE, Thornby J, David E, Weinstock J.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128166

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Significance of inducible cephalosporinase remaining in the experimentally infected rat granuloma pouch after beta-lactam therapy. by Araki H, Minami S, Watanabe Y, Yasuda T.; 1991 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284299

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Splenic and granuloma T-lymphocyte responses to fractionated soluble egg antigens of Schistosoma mansoni-infected mice. by Lukacs NW, Boros DL.; 1991 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258350

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Spontaneous and egg antigen-induced syntheses of immunoglobulin and antibody by spleen cells and hepatic granulomas of mice infected with Schistosoma japonicum. by Stavitsky AB, Garb KS.; 1984 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=261476

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Suppressive effect of interleukin-4 neutralization differs for granulomas around Schistosoma mansoni eggs injected into mice compared with those around eggs laid in infected mice. by Eltoum IA, Wynn TA, Poindexter RW, Finkelman FD, Lewis FA, Sher A, Cheever AW.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173338

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T-cell subsets in delayed-type hypersensitivity, protection, and granuloma formation in primary and secondary Listeria infection in mice: superior role of Lyt-2+ cells in acquired immunity. by Mielke ME, Ehlers S, Hahn H.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=259502

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Temporal and Spatial Arrangement of Lymphocytes within Lung Granulomas Induced by Aerosol Infection with Mycobacterium tuberculosis. by Gonzalez-Juarrero M, Turner OC, Turner J, Marietta P, Brooks JV, Orme IM.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98078

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The p47phox[minus sign]/[minus sign] Mouse Model of Chronic Granulomatous Disease Has Normal Granuloma Formation and Cytokine Responses to Mycobacterium avium and Schistosoma mansoni Eggs. by Segal BH, Doherty TM, Wynn TA, Cheever AW, Sher A, Holland SM.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96510

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Treatment of disseminated granuloma annulare with fumaric acid esters. by Kreuter A, Gambichler T, Altmeyer P, Brockmeyer NH.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101386

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Trehalose 6,6[prime prime or minute]-Dimycolate (Cord Factor) of Mycobacterium tuberculosis Induces Foreign-Body- and Hypersensitivity-Type Granulomas in Mice. by Yamagami H, Matsumoto T, Fujiwara N, Arakawa T, Kaneda K, Yano I, Kobayashi K.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97956

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Tumor necrosis factor receptor p55 is essential for intrahepatic granuloma formation and hepatocellular apoptosis in a murine model of bacterium-induced fulminant hepatitis. by Tsuji H, Harada A, Mukaida N, Nakanuma Y, Bluethmann H, Kaneko S, Yamakawa K, Nakamura SI, Kobayashi KI, Matsushima K.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175237

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Variable severity and Ia antigen expression in streptococcal-cell-wall-induced hepatic granulomas in rats. by Allen JB, Wilder RL.; 1987 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260392

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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 granulomas, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “granulomas” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for granulomas (hyperlinks lead to article summaries): •

A 10-year-old girl with renal failure and granulomas. Author(s): Soylemezoglu O, Ozkaya O, Derici U, Memis L, Kalman S, Buyan N. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 June; 39(6): 1323-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12046051

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A case of Wegener's granulomatosis without granulomas and with a negative CANCA. Author(s): Ahmad S, Reed D, Harisdangkul V. Source: J Miss State Med Assoc. 2002 April; 43(4): 104. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11989186

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A chemoattractant cytokine associated with granulomas in tuberculosis and silicosis. Author(s): Nau GJ, Guilfoile P, Chupp GL, Berman JS, Kim SJ, Kornfeld H, Young RA. Source: Proceedings of the National Academy of Sciences of the United States of America. 1997 June 10; 94(12): 6414-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9177232

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A clinicopathologic series of 22 cases of tonsillar granulomas. Author(s): Kardon DE, Thompson LD. Source: The Laryngoscope. 2000 March; 110(3 Pt 1): 476-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10718441

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 keyhole middle fossa approach to large cholesterol granulomas of the petrous apex. Author(s): Cristante L, Puchner MA. Source: Surgical Neurology. 2000 January; 53(1): 64-70; Discussion 70-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10697235

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A management strategy for vocal process granulomas. Author(s): Havas TE, Priestley J, Lowinger DS. Source: The Laryngoscope. 1999 February; 109(2 Pt 1): 301-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10890783

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A transient emergence of hepatic granulomas in a patient with chronic hepatitis B. Author(s): Kanno A, Murakami K. Source: The Tohoku Journal of Experimental Medicine. 1998 August; 185(4): 281-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9865475

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Adenolymphoma (Warthin's tumor) with multiple sarcoid-like granulomas. Author(s): Ryska A, Seifert G. Source: Pathology, Research and Practice. 1999; 195(12): 835-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10631719

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Allergic granulomas of the conjunctiva. Author(s): Teichmann KD, Huaman A. Source: Australian and New Zealand Journal of Ophthalmology. 1998 May; 26(2): 157-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9630297

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Aluminium-induced granulomas after inaccurate intradermal hyposensitization injections of aluminium-adsorbed depot preparations. Author(s): Vogelbruch M, Nuss B, Korner M, Kapp A, Kiehl P, Bohm W. Source: Allergy. 2000 September; 55(9): 883-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11003454

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Amiodarone-induced bone marrow granulomas. Author(s): Moran SK, Manoharan A. Source: Pathology. 2002 June; 34(3): 267-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12109789

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Amiodarone-induced bone marrow granulomas. Author(s): Boutros NY, Dilly S, Bevan DH. Source: Clinical and Laboratory Haematology. 2000 June; 22(3): 167-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10931167

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An intraperitoneal tumorous mass caused by granulomas of microfibrillar collagen hemostat (Avitene). Author(s): Nakajima M, Kamei T, Tomimatu K, Manabe T. Source: Archives of Pathology & Laboratory Medicine. 1995 December; 119(12): 1161-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7503666

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An outbreak of trematode-induced granulomas of the conjunctiva. Author(s): Rathinam S, Fritsche TR, Srinivasan M, Vijayalakshmi P, Read RW, Gautom R, Namperumalsamy P, Rao NA. Source: Ophthalmology. 2001 July; 108(7): 1223-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11425679

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Apoptosis in lymph node granulomas from white-tailed deer (Odocoileus virginianus) experimentally infected with Mycobacterium bovis. Author(s): Palmer MV, Gosch G, Lyon R, Waters WR, Whipple DL. Source: Journal of Comparative Pathology. 2002 July; 127(1): 7-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12354540

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Application of image analysis to the study of skin granulomas. Author(s): Esterre P, Guerret S, Grimaud JA. Source: Analytical Cellular Pathology : the Journal of the European Society for Analytical Cellular Pathology. 1995 April; 8(3): 191-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7547493

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Aspiration cytology of malignant neoplasms associated with granulomas and granuloma-like features: diagnostic dilemmas. Author(s): Khurana KK, Stanley MW, Powers CN, Pitman MB. Source: Cancer. 1998 April 25; 84(2): 84-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9570210

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Association of man-made mineral fibre exposure and sarcoidlike granulomas. Author(s): Drent M, Bomans PH, Van Suylen RJ, Lamers RJ, Bast A, Wouters EF. Source: Respiratory Medicine. 2000 August; 94(8): 815-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10955759

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Attempted suicide by intravenous injection of mercury: a rare cause of cardiac granulomas. A case report. Author(s): Kedziora A, Duflou J. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 1995 June; 16(2): 172-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7572878

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Basement membrane-type heparan sulfate proteoglycan (perlecan) and low-density lipoprotein (LDL) are co-localized in granulation tissues: a possible pathogenesis of cholesterol granulomas in jaw cysts. Author(s): Yamazaki M, Cheng J, Hao N, Takagi R, Jimi S, Itabe H, Saku T. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2004 March; 33(3): 177-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15128060

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BCG immunotherapy: be cautious of granulomas. Disseminated BCG infection and mycotic aneurysm as late complications of intravesical BCG instillations. Author(s): Kamphuis JT, Buiting AG, Misere JF, van Berge Henegouwen DP, van Soolingen D, Rensma PL. Source: The Netherlands Journal of Medicine. 2001 February; 58(2): 71-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11166448

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Beau's lines and pyogenic granulomas following hand trauma. Author(s): Price MA, Bruce S, Waidhofer W, Weaver SM. Source: Cutis; Cutaneous Medicine for the Practitioner. 1994 October; 54(4): 246-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7805406

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Bee-sting granulomas in the skin. Author(s): Lee CW, Cho JH, Yu HJ, Yang HY, Park CK, Park MH. Source: Dermatology (Basel, Switzerland). 1996; 193(4): 355-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8993970

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Bilateral central giant cell granulomas in a patient with neurofibromatosis: report of a case and review of the literature. Author(s): Ardekian L, Manor R, Peled M, Laufer D. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1999 July; 57(7): 869-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10416639

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Bilateral cholesterol granulomas of the temporal bone. Author(s): Eby TL, Guthrie BL. Source: Orl; Journal for Oto-Rhino-Laryngology and Its Related Specialties. 1998 November-December; 60(6): 318-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9742279

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Bilateral external chalazia presenting as granulomas of the lower eyelids. Author(s): Williams HC, Aclimandos WA, Salisbury J. Source: Clinical and Experimental Dermatology. 1992 November; 17(6): 441-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1486713

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Bone marrow fibrin ring granulomas and cytomegalovirus infection. Author(s): Young JF, Goulian M. Source: American Journal of Clinical Pathology. 1993 January; 99(1): 65-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8380679

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Bone marrow fibrin-ring (doughnut) granulomas and peripheral T-cell lymphoma: an exceptional association. Author(s): Raya Sanchez JM, Arguelles HA, Brito Barroso ML, Nieto LH. Source: Haematologica. 2001 January; 86(1): 112. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11146588

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Bone marrow granulomas associated with chronic natural killer cell lymphocytosis. Author(s): Tefferi A, Li CY. Source: American Journal of Hematology. 1997 March; 54(3): 258-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9067507

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Bone marrow granulomas in hairy cell leukaemia following 2-chlorodeoxyadenosine therapy. Author(s): Franco V, Florena AM, Quintini G, Musso M. Source: Histopathology. 1994 March; 24(3): 271-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7911119

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Bone marrow granulomas in hairy cell leukaemia. Author(s): Schmidt HH, Hofler G, Beham-Schmid C, Sill H, Linkesch W. Source: Histopathology. 1996 September; 29(3): 291-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8884362

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Bone marrow granulomas in infiltrating lobular breast cancer. Author(s): Kettle P, Allen DC. Source: Journal of Clinical Pathology. 1997 February; 50(2): 166-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9155702

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Bone marrow granulomas possibly associated with amiodarone. Author(s): Yamreudeewong W, McIntyre WW, Sun TJ, Ranelli PL. Source: Pharmacotherapy. 2000 July; 20(7): 855-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10907978

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Bone marrow granulomas, fever, pancytopenia, and lupus-like syndrome due to tocainide. Author(s): Gelfand MS, Yunus F, White FL. Source: Southern Medical Journal. 1994 August; 87(8): 839-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8052899

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Brain granulomas in neurocysticercosis patients are associated with a Th1 and Th2 profile. Author(s): Restrepo BI, Alvarez JI, Castano JA, Arias LF, Restrepo M, Trujillo J, Colegial CH, Teale JM. Source: Infection and Immunity. 2001 July; 69(7): 4554-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11401999

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Breast carcinoma associated with necrotic granulomas in axillary lymph nodes. Author(s): Sethi S, Carter D. Source: Annals of Diagnostic Pathology. 1998 December; 2(6): 370-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9930574

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Breast implant-related silicone granulomas: the literature and the litigation. Author(s): Austad ED. Source: Plastic and Reconstructive Surgery. 2002 April 15; 109(5): 1724-30; Discussion 1731-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11932626

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Bronchoalveolar lavage fluid granulomas in a case of severe sarcoidosis. Author(s): Hendricks MV, Crosby JH, Davis WB. Source: American Journal of Respiratory and Critical Care Medicine. 1999 August; 160(2): 730-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10430753

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Buttock granulomas: a consequence of intramuscular injection of Sandostatin detected by In-111 octreoscan. Author(s): Rideout DJ, Graham MM. Source: Clinical Nuclear Medicine. 2001 July; 26(7): 650. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11416760

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Calcitonin treatment for central giant cell granulomas of the mandible: report of two cases. Author(s): Pogrel MA, Regezi JA, Harris ST, Goldring SR. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1999 July; 57(7): 848-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10416634

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Candida albicans cerebral granulomas associated with a nonfunctional cerebrospinal fluid shunt: case report. Author(s): Soto-Hernandez JL, Ramirez-Crescencio MA, Moreno Estrada VM, del Valle Robles R. Source: Neurosurgery. 2000 October; 47(4): 973-6; Discussion 976-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11014440

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Central giant cell granulomas: a systematic review of the radiographic characteristics with the addition of 20 new cases. Author(s): Stavropoulos F, Katz J. Source: Dento Maxillo Facial Radiology. 2002 July; 31(4): 213-7. Review. Erratum In: Dentomaxillofac Radiol 2002 November; 31(6): 394. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087437

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Cholesterol granulomas of the lungs associated with microangiopathic hemolytic anemia and thrombocytopenia in pulmonary hypertension. Author(s): Fischer EG, Marek JM, Morris A, Nashelsky MB. Source: Archives of Pathology & Laboratory Medicine. 2000 December; 124(12): 1813-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11100063

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Choroidal granulomas in systemic sarcoidosis. Author(s): Desai UR, Tawansy KA, Joondeph BC, Schiffman RM. Source: Retina (Philadelphia, Pa.). 2001; 21(1): 40-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11217928

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Clinical correlates of granulomas in muscle. Author(s): Mozaffar T, Lopate G, Pestronk A. Source: Journal of Neurology. 1998 August; 245(8): 519-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9747915

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Clinical evolution of laryngeal granulomas: treatment and prognosis. Author(s): de Lima Pontes PA, De Biase NG, Gadelha EC. Source: The Laryngoscope. 1999 February; 109(2 Pt 1): 289-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10890781

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Coexistence of histoplasma granulomas and Warthin's tumor in the submaxillary salivary gland. Author(s): Udoji WC. Source: Tenn Med. 1999 May; 92(5): 175-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10230319

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Comparison of the T cell patterns in leprous and cutaneous sarcoid granulomas. Presence of Valpha24-invariant natural killer T cells in T-cell-reactive leprosy together with a highly biased T cell receptor Valpha repertoire. Author(s): Mempel M, Flageul B, Suarez F, Ronet C, Dubertret L, Kourilsky P, Gachelin G, Musette P. Source: American Journal of Pathology. 2000 August; 157(2): 509-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10934154

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Contact granulomas. Author(s): Hynes B. Source: The Journal of Otolaryngology. 1998 October; 27(5): 310. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9800633

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Cutaneous and hepatic granulomas in a young woman with common variable immunodeficiency. Author(s): Cornejo P, Romero A, Lopez S, Guerra A, Gil R, Iglesias L. Source: The British Journal of Dermatology. 1999 March; 140(3): 546-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10233289

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Cutaneous granulomas associated with high-grade T-cell non-Hodgkin's lymphoma. Author(s): Farrell AM, Henry K, Woodrow D, Francis N, Newlands ES, Mitchell DN, Cream JJ. Source: The British Journal of Dermatology. 1999 January; 140(1): 145-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10215786

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Cutaneous granulomas caused by an aluminum-zirconium complex: an ingredient of antiperspirants. Author(s): Montemarano AD, Sau P, Johnson FB, James WD. Source: Journal of the American Academy of Dermatology. 1997 September; 37(3 Pt 1): 496-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9308573

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Cutaneous granulomas in a patient with common variable immunodeficiency. Author(s): Alvarez-Cuesta C, Molinos L, Cascante JA, Soler T, Perez-Oliva N. Source: Acta Dermato-Venereologica. 1999 July; 79(4): 334. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10430004

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Cutaneous granulomas masquerading as tuberculoid leprosy in a patient with congenital combined immunodeficiency. Author(s): Krupnick AI, Shim H, Phelps RG, Cunningham-Rundles C, Sapadin AN. Source: The Mount Sinai Journal of Medicine, New York. 2001 September-October; 68(45): 326-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11514920

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Cutaneous granulomas with two clinical presentations in a patient with common variable immunodeficiency. Author(s): Ziegler EM, Seung LM, Soltani K, Medenica MM. Source: Journal of the American Academy of Dermatology. 1997 September; 37(3 Pt 1): 499-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9308574

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Cutaneous sarcoid foreign body granulomas developing in sites of previous skin injury after systemic interferon-alpha treatment for chronic hepatitis C. Author(s): Eberlein-Konig B, Hein R, Abeck D, Engst R, Ring J. Source: The British Journal of Dermatology. 1999 February; 140(2): 370-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10233247

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Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response. Author(s): Bergeron A, Bonay M, Kambouchner M, Lecossier D, Riquet M, Soler P, Hance A, Tazi A. Source: Journal of Immunology (Baltimore, Md. : 1950). 1997 September 15; 159(6): 303443. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9300729

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Cytology of peritoneal keratin granulomas. Author(s): Chen KT. Source: Diagnostic Cytopathology. 1999 February; 20(2): 105-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9951608

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Cytotoxic T lymphocytes versus streptococcal colonization in periapical granulomas. Author(s): Hren NI, Gubina M, Ihan A. Source: Journal of Endodontics. 1999 April; 25(4): 239-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10425947

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Defining epithelioid cell granulomas. Author(s): Dundas SA, Mansour P. Source: Journal of Clinical Pathology. 1997 October; 50(10): 880. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9462278

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Delayed appearance of carbon granulomas of the scalp after use of carbon fiber pins for refixation of a stereotactic head frame. Case report. Author(s): McCormick WE, Barnett GH, Peereboom DM, Stevens GH, Biscotti CV. Source: Journal of Neurosurgery. 2001 July; 95(1): 129-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11453383

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Delayed relapse of Churg-Strauss syndrome manifesting as colon ulcers with mucosal granulomas: 3 cases. Author(s): Memain N, De BM, Guillevin L, Wechsler B, Meyer O. Source: The Journal of Rheumatology. 2002 February; 29(2): 388-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11838861

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Delayed skin reaction to Red Sea coral injury showing superficial granulomas and atypical CD30+ lymphocytes: report of a case. Author(s): Miracco C, Lalinga AV, Sbano P, Rubegni P, Romano C. Source: The British Journal of Dermatology. 2001 November; 145(5): 849-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11736921

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Detection of antibodies to Pneumocystis carinii in bronchoalveolar lavage fluid by immunoreactivity to Pneumocystis carinii within alveoli, granulomas, and disseminated sites. Author(s): Blumenfeld W, McCook O, Griffiss JM. Source: Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc. 1992 March; 5(2): 107-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1574487

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Detection of tumour necrosis factor alpha in sarcoidosis and tuberculosis granulomas using in situ hybridisation. Author(s): Myatt N, Coghill G, Morrison K, Jones D, Cree IA. Source: Journal of Clinical Pathology. 1994 May; 47(5): 423-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8027394

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Development of progressive pulmonary interstitial and intra-alveolar cholesterol granulomas (PICG) associated with therapy-resistant chronic systemic juvenile arthritis (CJA). Author(s): Schultz R, Mattila J, Gappa M, Verronen P. Source: Pediatric Pulmonology. 2001 November; 32(5): 397-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11596165

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Diagnostic significance of epithelioid granulomas in Crohn's disease in children. Multicenter Paediatric Crohn's Disease Study Group. Author(s): Keller KM, Bender SW, Kirchmann H, Ball F, Schmitz-Moormann P, Wirth S, Baumann W. Source: Journal of Pediatric Gastroenterology and Nutrition. 1990 January; 10(1): 27-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2182814

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Differentiating solitary small cysticercus granulomas and tuberculomas in patients with epilepsy. Clinical and computerized tomographic criteria. Author(s): Rajshekhar V, Haran RP, Prakash GS, Chandy MJ. Source: Journal of Neurosurgery. 1993 March; 78(3): 402-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8433141

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Differentiation of periapical granulomas and radicular cysts by digital radiometric analysis. Author(s): Shrout MK, Hall JM, Hildebolt CE. Source: Oral Surg Oral Med Oral Pathol. 1993 September; 76(3): 356-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8378051

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Difficulties in endoscopic removal of Teflon granulomas of the vocal fold. Author(s): Ossoff RH, Koriwchak MJ, Netterville JL, Duncavage JA. Source: The Annals of Otology, Rhinology, and Laryngology. 1993 June; 102(6): 405-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8512266

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Diffuse progressive pulmonary interstitial and intra-alveolar cholesterol granulomas in childhood. Author(s): Sato K, Takahashi H, Amano H, Uekusa T, Dambara T, Kira S. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1996 November; 9(11): 2419-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8947094

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Disseminated coccidioidomycosis presenting as facial granulomas in pregnancy: a report of two cases and a review of the literature. Author(s): Hadsall FJ, Acquarelli MJ. Source: The Laryngoscope. 1973 January; 83(1): 51-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4683913

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Disseminated Nocardia asteroides presenting as pulmonary non-caseating granulomas in a patient with Waldenstrom macroglobulinemia. Author(s): Apisarnthanarak A, Razavi B, Bailey T. Source: Infection. 2002 January; 30(1): 38-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11876515

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Disseminated pulmonary granulomas after intravesical bacillus Calmette-Guerin immunotherapy. Author(s): De Diego A, Rogado MC, Prieto M, Nauffal D, Perpina M. Source: Respiration; International Review of Thoracic Diseases. 1997; 64(4): 304-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9257368

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Distant cutaneous granulomas after bacille Calmette-Guerin immunotherapy for malignant melanoma: case for direct infection. Author(s): Moff SL, Corey GR, Gottfredsson M. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1999 December; 29(6): 1569-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10585816

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Distribution of IFN-gamma, IL-4 and TNF-alpha protein and CD8 T cells producing IL-12p40 mRNA in human lung tuberculous granulomas. Author(s): Fenhalls G, Stevens L, Bezuidenhout J, Amphlett GE, Duncan K, Bardin P, Lukey PT. Source: Immunology. 2002 March; 105(3): 325-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11918694

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Does treatment change the outcome of seizures and computerized tomographic lesions in intracranial granulomas? Author(s): Rajadhyaksha S, Shah KN, Kanhere S, Naik N, Mehta R. Source: Journal of Tropical Pediatrics. 1999 June; 45(3): 161-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10401195

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Double-ligature: a treatment for pedunculated umbilical granulomas in children. Author(s): Lotan G, Klin B, Efrati Y. Source: American Family Physician. 2002 May 15; 65(10): 2067-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12046774

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Dysphagia due to mediastinal granulomas: diagnosis with endoscopic ultrasonography. Author(s): Savides TJ, Gress FG, Wheat LJ, Ikenberry S, Hawes RH. Source: Gastroenterology. 1995 August; 109(2): 366-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7615184

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Elemental mercury foreign body granulomas. Author(s): Allen CC, Lund KA, Treadwell P. Source: International Journal of Dermatology. 1992 May; 31(5): 353-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1587668

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Enhanced expression of human metalloelastase (MMP-12) in cutaneous granulomas and macrophage migration. Author(s): Vaalamo M, Kariniemi AL, Shapiro SD, Saarialho-Kere U. Source: The Journal of Investigative Dermatology. 1999 April; 112(4): 499-505. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10201535

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Enlarging solitary cysticercus granulomas. Author(s): Rajshekhar V, Chandy MJ. Source: Journal of Neurosurgery. 1994 May; 80(5): 840-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8169623

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Eosinophils from schistosome-induced hepatic granulomas produce superoxide and hydroxyl radical. Author(s): McCormick ML, Metwali A, Railsback MA, Weinstock JV, Britigan BE. Source: Journal of Immunology (Baltimore, Md. : 1950). 1996 December 1; 157(11): 500915. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8943408

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Epithelioid cell granulomas in chronic hepatitis C: immunohistochemical character and histological marker of favourable response to interferon-alpha therapy. Author(s): Harada K, Minato H, Hiramatsu K, Nakanuma Y. Source: Histopathology. 1998 September; 33(3): 216-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9777387

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Epithelioid granulomas as main clinical manifestation at the outset of non-Hodgkin's lymphoma: report of two cases. Author(s): Lerza R, Schenone E, Barsotti BP, Botta M, Arboscello E, Truini M, Bogliolo G, Pannacciulli I. Source: Oncology Research. 2002; 13(1): 55-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12201675

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Epithelioid granulomas in Hodgkin's disease--prognostic significance. Author(s): Chopra R, Rana R, Zachariah A, Mahajan MK, Prabhakar BR. Source: Indian J Pathol Microbiol. 1995 October; 38(4): 427-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9726157

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Epithelioid granulomas in small noncleaved cell lymphoma. Author(s): Chan JK, Tsang WY. Source: The American Journal of Surgical Pathology. 1993 October; 17(10): 1068. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8372946

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Eruptive pyogenic granulomas: a successfully treated patient and review of the literature. Author(s): Shah M, Kingston TP, Cotterill JA. Source: The British Journal of Dermatology. 1995 November; 133(5): 795-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8555038

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Estrogen and progesterone receptors in the peripheral giant cell granulomas of the oral cavity. Author(s): Gunhan M, Gunhan O, Celasun B, Mutlu M, Bostanci H. Source: J Oral Sci. 1998 June; 40(2): 57-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9680761

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Estrogen receptor proteins in peripheral and central giant cell granulomas of the jaws. Author(s): Kamel A, Elsharkawy TM. Source: Egypt Dent J. 1995 July; 41(3): 1243-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9497663

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Evolution of sarcoid granulomas of the retina. Author(s): Frohman L, Grigorian R, Slamovits T. Source: American Journal of Ophthalmology. 2001 May; 131(5): 661-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11336948

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Excessive fibrosis of supraclavicular lymph-node granulomas in a patient with progressive systemic sclerosis. Author(s): Andonopoulos AP, Tzanakakis G. Source: Rheumatology International. 1993; 12(6): 255-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8484100

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Expression of costimulatory molecules B7-1 and B7-2 in macrophages and granulomas of Crohn's disease: demonstration of cell-to-cell contact with T lymphocytes. Author(s): Hara J, Ohtani H, Matsumoto T, Nakamura S, Kitano A, Arakawa T, Nagura H, Kobayashi K. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1997 August; 77(2): 175-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9274860

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Expression of inducible nitric oxide synthase in human granulomas and histiocytic reactions. Author(s): Facchetti F, Vermi W, Fiorentini S, Chilosi M, Caruso A, Duse M, Notarangelo LD, Badolato R. Source: American Journal of Pathology. 1999 January; 154(1): 145-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9916929

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Expression of intercellular adhesion molecule-1 and lymphocytefunction-associated antigen-1 in experimental Schistosoma mansoni infection and in synchronous periparticular hepatic granulomas in mice: immunohistochemistry, confocal laser scanning microscopy, and immunoelectron microscopy. Author(s): Jacobs W, Bogers J, Deelder A, Van Marck E. Source: Parasitology Research. 1997; 83(5): 405-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9197386

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Expression of regulatory apoptotic proteins in peripheral giant cell granulomas and lesions containing osteoclast-like giant cells. Author(s): Pammer J, Weninger W, Hulla H, Mazal P, Horvat R. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1998 July; 27(6): 267-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9707279

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Expression of thioredoxin in granulomas of sarcoidosis: possible role in the development of T lymphocyte activation. Author(s): Koura T, Gon Y, Hashimoto S, Azuma A, Kudoh S, Fukuda Y, Sugawara I, Yodoi J, Horie T. Source: Thorax. 2000 September; 55(9): 755-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10950894

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Extrahepatic biliary atresia with palisading granulomas. Author(s): Calder CJ, Hubscher SG. Source: Histopathology. 1993 December; 23(6): 585-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8314247

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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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12174116

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F.I.GU.R.E.: facial idiopathic granulomas with regressive evolution. is 'lupus miliaris disseminatus faciei' still an acceptable diagnosis in the third millennium? Author(s): Skowron F, Causeret AS, Pabion C, Viallard AM, Balme B, Thomas L. Source: Dermatology (Basel, Switzerland). 2000; 201(4): 287-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11146335

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Fansidar and hepatic granulomas. Author(s): Lazar HP, Murphy RL, Phair JP. Source: Annals of Internal Medicine. 1985 May; 102(5): 722. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3985527

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Fibrin ring granulomas and allopurinol. Author(s): Stricker BH, Blok AP, Babany G, Benhamou JP. Source: Gastroenterology. 1989 April; 96(4): 1199-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2925064

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Fibrin ring granulomas in hepatitis A. Author(s): Ruel M, Sevestre H, Henry-Biabaud E, Courouce AM, Capron JP, Erlinger S. Source: Digestive Diseases and Sciences. 1992 December; 37(12): 1915-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1473440

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Fibrin-ring granulomas: a non-specific reaction to liver injury? Author(s): Murphy E, Griffiths MR, Hunter JA, Burt AD. Source: Histopathology. 1991 July; 19(1): 91-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1916692

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Fine-needle aspiration cytology of silicone granulomas in the augmented breast. Author(s): Dodd LG, Sneige N, Reece GP, Fornage B. Source: Diagnostic Cytopathology. 1993 October; 9(5): 498-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8287755

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Fine-needle aspiration cytology of suture granulomas of the breast: a potential pitfall in the cytologic diagnosis of recurrent breast cancer. Author(s): Maygarden SJ, Novotny DB, Johnson DE, Powers CN, Frable WJ. Source: Diagnostic Cytopathology. 1994; 10(2): 175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8187601

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Foamy cells in itp spleens and in granulomas induced by murine platelets, commercialized phospholipids, and erythrocyte membrane. Histological and ultrastructural studies. Author(s): Ishihara T, Akizuki S, Yamanami S, Yamashita Y, Yokota T, Okuzono Y, Takahashi M, Kamei T, Uchino F, Matsumoto N. Source: Acta Pathol Jpn. 1983 September; 33(5): 943-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6685966

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Focal prostatic granulomas rheumatoid like--probably iatrogenic in origin. Author(s): Pieterse AS, Aarons I, Jose JS. Source: Pathology. 1984 April; 16(2): 174-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6462781

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Foreign body episcleral granulomas complicating intravitreal silicone oil tamponade: a clinicopathological study. Author(s): Srinivasan S, Singh AK, Desai SP, Talbot JF, Parsons MA. Source: Ophthalmology. 2003 September; 110(9): 1837-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13129886

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Foreign body granulomas caused by polymethylmethacrylate microspheres: an added perspective. Author(s): Thaler MP. Source: Archives of Dermatology. 2003 November; 139(11): 1505-6; Author Reply 1506. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623717

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Foreign body granulomas caused by polymethylmethacrylate microspheres: successful treatment with allopurinol. Author(s): Reisberger EM, Landthaler M, Wiest L, Schroder J, Stolz W. Source: Archives of Dermatology. 2003 January; 139(1): 17-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12533157

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Foreign body granulomas due to injectable aesthetic microimplants. Author(s): Rudolph CM, Soyer HP, Schuller-Petrovic S, Kerl H. Source: The American Journal of Surgical Pathology. 1999 January; 23(1): 113-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9888711

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Foreign body granulomas in normal ovaries. Author(s): Mostafa SA, Bargeron CB, Flower RW, Rosenshein NB, Parmley TH, Woodruff JD. Source: Obstetrics and Gynecology. 1985 November; 66(5): 701-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3903583

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Foreign body granulomas in the head and neck. Author(s): Bryarly RC Jr, Stucker FJ Jr. Source: Otolaryngologic Clinics of North America. 1982 August; 15(3): 553-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6290960

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Foreign body granulomas of the breast presenting as bilateral spiculated masses. Author(s): Han BK, Choe YH, Ko YH, Nam SJ, Yang JH. Source: Korean Journal of Radiology : Official Journal of the Korean Radiological Society. 2001 April-June; 2(2): 113-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11752980

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Foreign body pulmonary granulomas in an abuser of nasally inhaled drugs. Author(s): Johnson DC, Petru A, Azimi PH. Source: Pediatrics. 1991 July; 88(1): 159-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2057254

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Formation of palisading granulomas in a patient with chronic cutaneous cryptococcosis. Author(s): Leidel GD, Metcalf JS. Source: The American Journal of Dermatopathology. 1989 December; 11(6): 560-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2604024

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Four monoclonal antibodies, AMH-1, -2, -3, and -4, give varied reactivities with monocytes, alveolar macrophages, and epithelioid-cell granulomas. Author(s): Akiyama J, Chida K, Sato A, Yamashita A. Source: Journal of Clinical Immunology. 1988 September; 8(5): 372-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3182965

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Fungal and parasitic granulomas of the head and neck. Author(s): Schlech WF 3rd, Carden GA. Source: Otolaryngologic Clinics of North America. 1982 August; 15(3): 493-513. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6752819

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Gallstone spilt granulomas caused by laparoscopic cholecystectomy. Author(s): Xu Y, Zheng P. Source: Chinese Medical Journal. 1998 January; 111(1): 92-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10322667

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Gallstones split at laparoscopic cholecystectomy: a new cause of intraperitoneal granulomas. Author(s): Warren CW, Wyatt JI. Source: Journal of Clinical Pathology. 1996 January; 49(1): 84-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8666694

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Gastric lymphoma associated with mucosal and nodal granulomas: a new differential diagnosis in granulomatous gastritis. Author(s): Leach IH, Maclennan KA. Source: Histopathology. 1990 July; 17(1): 87-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2227834

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Gastric T-cell lymphoma presenting with epithelioid granulomas mimicking tuberculosis in regional lymph nodes. Author(s): Asakawa H, Tsuji M, Tokumine Y, Kashihara T, Okuno M, Takenaka R, Kawakami F. Source: Journal of Gastroenterology. 2001 March; 36(3): 190-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11291883

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Generalized sarcoidlike granulomas with systemic angiitis, crescentic glomerulonephritis, and pulmonary hemorrhage. Report of an autopsy case. Author(s): Shintaku M, Mase K, Ohtsuki H, Yasumizu R, Yasunaga K, Ikehara S. Source: Archives of Pathology & Laboratory Medicine. 1989 November; 113(11): 1295-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2640555

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Giant cell vasculitis with extravascular granulomas in an adolescent. Author(s): Faye-Petersen O, Frankel SR, Schulman PE, Raucher H, Spiera H, Dische MR, Speira H. Source: Pediatr Pathol. 1991 March-April; 11(2): 281-95. Erratum In: Pediatr Pathol 1991 September-October; 11(5): Following 797. Speira H[corrected to Spiera H]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2052510

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Granulomas and hepatitis C. Author(s): Goldin RD, Levine TS, Foster GR, Thomas HC. Source: Histopathology. 1996 March; 28(3): 265-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8729048

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Granulomas are not just gizmos for immunologists. Author(s): Doenhoff MJ. Source: Trends in Immunology. 2003 April; 24(4): 168-9; Author Reply 169-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12697442

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Granulomas associated with tetanus toxoid immunization. Author(s): Cominos D, Strutton G, Busmanis I. Source: The American Journal of Dermatopathology. 1993 April; 15(2): 114-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8494110

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Granulomas in edentulous jaws. Author(s): Adkins KF. Source: N Z Dent J. 1972 July; 68(313): 209-12. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4567496

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Granulomas in hepatocellular carcinoma induced by lipiodolized SMANCS, a polymer-conjugated derivative of neocarzinostatin. Author(s): Ichikawa T, Takagi H, Yamada T, Abe T, Ito H, Kojiro M, Mori M. Source: Histopathology. 2002 June; 40(6): 579-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12047775

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Granulomas in primary sclerosing cholangitis. Author(s): Ludwig J, Colina F, Poterucha JJ. Source: Liver. 1995 December; 15(6): 307-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8609810

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Granulomas in schistosome and mycobacterial infections: a model of local immune responses. Author(s): Sandor M, Weinstock JV, Wynn TA. Source: Trends in Immunology. 2003 January; 24(1): 44-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495724

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Granulomas in the diagnosis of intestinal Crohn's disease: a myth exploded? Author(s): Shepherd NA. Source: Histopathology. 2002 August; 41(2): 166-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12147095

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Granulomas in the livers of humans and Fischer rats associated with the ingestion of mineral hydrocarbons: a comparison. Author(s): Fleming KA, Zimmerman H, Shubik P. Source: Regulatory Toxicology and Pharmacology : Rtp. 1998 February; 27(1 Pt 1): 75-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9629598

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Granulomas of the appendix: is it Crohn's disease? Author(s): Wettergren A, Munkholm P, Larsen LG, Meinecke B, Langholz E, Jess P, Binder V. Source: Scandinavian Journal of Gastroenterology. 1991 September; 26(9): 961-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1947789

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Granulomas of the gut in Crohn's disease. A step sectioning study. Author(s): Kuramoto S, Oohara T, Ihara O, Shimazu R, Kondo Y. Source: Diseases of the Colon and Rectum. 1987 January; 30(1): 6-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3803110

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Granulomas of the kidney induced by Bacillus Calmette Guerin (BCG) Author(s): Kondratowicz GM, Wallace DM. Source: Journal of Clinical Pathology. 1989 April; 42(4): 442. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2715357

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Ground-glass attenuation, nodules, alveolitis, and sarcoid granulomas. Author(s): Muller NL, Miller RR. Source: Radiology. 1993 October; 189(1): 31-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8372213

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Guidelines for the diagnosis and interpretation of hepatic granulomas. Author(s): Denk H, Scheuer PJ, Baptista A, Bianchi L, Callea F, De Groote J, Desmet VJ, Gudat F, Ishak KG, Korb G, et al. Source: Histopathology. 1994 September; 25(3): 209-18. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7821888

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Heavy metal injection granulomas: a source of diagnostic confusion : a composite case report. Author(s): Tamai J, Shaw JA. Source: The Journal of Bone and Joint Surgery. American Volume. 2002 May; 84-A(5): 800-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12004024

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Hemophagocytosis and granulomas in the bone marrow of a child with Down syndrome. Author(s): Sakhalkar VS, Rao SP, Gottessman SR, Miller ST. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2001 December; 23(9): 623-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11902310

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Hepatic fibrin-ring granulomas in a patient with hepatitis A. Author(s): Ponz E, Garcia-Pagan JC, Bruguera M, Bruix J, Rodes J. Source: Gastroenterology. 1991 January; 100(1): 268-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1983832

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Hepatic fibrin-ring granulomas in giant cell arteritis. Author(s): de Bayser L, Roblot P, Ramassamy A, Silvain C, Levillain P, Becq-Giraudon B. Source: Gastroenterology. 1993 July; 105(1): 272-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8514044

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Hepatic fibrin-ring granulomas in granulomatous hepatitis: report of four cases and review of the literature. Author(s): Tjwa M, De Hertogh G, Neuville B, Roskams T, Nevens F, Van Steenbergen W. Source: Acta Clin Belg. 2001 November-December; 56(6): 341-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11881318

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Hepatic fibrin-ring granulomas. Author(s): Roberts IS, Armstrong GR. Source: Histopathology. 1992 June; 20(6): 549. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1607158

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Hepatic fibrin-ring granulomas: a clinicopathologic study of 23 patients. Author(s): Marazuela M, Moreno A, Yebra M, Cerezo E, Gomez-Gesto C, Vargas JA. Source: Human Pathology. 1991 June; 22(6): 607-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1864592

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Hepatic granulomas and hepatic sarcoidosis. Author(s): Valla DC, Benhamou JP. Source: Clinics in Liver Disease. 2000 February; 4(1): 269-85, Ix-X. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11232190

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Hepatic granulomas due to visceral larva migrans in adults: appearance on US and MRI. Author(s): Jain R, Sawhney S, Bhargava DK, Panda SK, Berry M. Source: Abdominal Imaging. 1994 May-June; 19(3): 253-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8019356

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Hepatic granulomas following liver transplantation. Clinicopathologic features in 42 patients. Author(s): Ferrell LD, Lee R, Brixko C, Bass NM, Lake JR, Roberts JP, Ascher N, Rabkin J. Source: Transplantation. 1995 November 15; 60(9): 926-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7491695

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Hepatic granulomas in children. A clinicopathologic analysis of 23 cases including polymerase chain reaction for histoplasma. Author(s): Collins MH, Jiang B, Croffie JM, Chong SK, Lee CH. Source: The American Journal of Surgical Pathology. 1996 March; 20(3): 332-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8772787

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Hepatic granulomas in chronic hepatitis C. Author(s): Mert A, Tabak F, Ozaras R, Tahan V, Senturk H, Ozbay G. Source: Journal of Clinical Gastroenterology. 2001 October; 33(4): 342-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11588555

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Hepatic granulomas in Northern Ireland: a thirteen year review. Author(s): McCluggage WG, Sloan JM. Source: Histopathology. 1994 September; 25(3): 219-28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7821889

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Hepatic granulomas. Author(s): Lefkowitch JH. Source: Journal of Hepatology. 1999; 30 Suppl 1: 40-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10370899

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Hepatic granulomas. Author(s): Ho KT. Source: Singapore Med J. 1990 October; 31(5): 411-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2259932

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Hepatic granulomas--an experience over the last 8 years. Author(s): Chong RS, Ng HS, Teh LB, Ho JM. Source: Singapore Med J. 1990 October; 31(5): 422-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2259936

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Histologic, ultrastructural, and immunocytochemical features of the granulomas seen in a child with the syndrome of familial granulomatous arthritis, uveitis, and rash. Author(s): de Chadarevian JP, Raphael SA, Murphy GF. Source: Archives of Pathology & Laboratory Medicine. 1993 October; 117(10): 1050-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8215830

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Histological findings of human leprosy periapical granulomas. Author(s): Tani-Ishii N, Osada T, Watanabe Y, Umemoto T. Source: Journal of Endodontics. 1996 March; 22(3): 120-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8618092

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Human herpesvirus type 8 is not associated with pyogenic granulomas with satellite recurrence. Author(s): De Aloe G, Rubegni P, Pacenti L, Miracco C, Fimiani M. Source: The British Journal of Dermatology. 2001 January; 144(1): 202-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11167718

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Hydroxychloroquine is effective therapy for control of cutaneous sarcoidal granulomas. Author(s): Jones E, Callen JP. Source: Journal of the American Academy of Dermatology. 1990 September; 23(3 Pt 1): 487-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2212149

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Identification of Mycobacterium marinum in sea-urchin granulomas. Author(s): De la Torre C, Vega A, Carracedo A, Toribio J. Source: The British Journal of Dermatology. 2001 July; 145(1): 114-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11453918

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Images in clinical medicine. Pulmonary cryptococcal granulomas. Author(s): Fairhurst RM, Pegues DA. Source: The New England Journal of Medicine. 2002 August 15; 347(7): 497. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12181404

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Images in clinical medicine. Pulmonary granulomas in an intravenous drug user. Author(s): Lemoine R, Dusmet M. Source: The New England Journal of Medicine. 2000 November 2; 343(18): 1312. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11058676

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Imaging of carbon granulomas of the breast following carbon track localization. Author(s): Patrikeos A, Wylie EJ, Bourke A, Frost F. Source: Clinical Radiology. 1998 November; 53(11): 845-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9833790

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Immediate reaugmentation of the breasts using bilaterally divided TRAM flaps after removing injected silicone gel and granulomas. Author(s): Aoki R, Mitsuhashi K, Hyakusoku H. Source: Aesthetic Plastic Surgery. 1997 July-August; 21(4): 276-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9263552

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Immunohistochemical localization of activated and mature CD83+ dendritic cells in granulomas of sporotrichosis. Author(s): Koga T, Duan H, Urabe K, Furue M. Source: European Journal of Dermatology : Ejd. 2001 November-December; 11(6): 527-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11701401

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Immunohistochemical localization of somatostatin receptor sst2A in sarcoid granulomas. Author(s): ten Bokum AM, Hofland LJ, de Jong G, Bouma J, Melief MJ, Kwekkeboom DJ, Schonbrunn A, Mooy CM, Laman JD, Lamberts SW, van Hagen PM. Source: European Journal of Clinical Investigation. 1999 July; 29(7): 630-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10411670

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Immunohistological identification of epithelioid cell granulomas in Crohn's disease and its diagnostic values especially in the differentiation from ulcerative colitis. Author(s): Nakashima H. Source: J Med Dent Sci. 1998 December; 45(4): 211-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11186213

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Importance of cryptolytic lesions and pericryptal granulomas in inflammatory bowel disease. Author(s): Warren BF, Shepherd NA, Price AB, Williams GT. Source: Journal of Clinical Pathology. 1997 October; 50(10): 880-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9462279

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Importance of cryptolytic lesions and pericryptal granulomas in inflammatory bowel disease. Author(s): Lee FD, Maguire C, Obeidat W, Russell RI. Source: Journal of Clinical Pathology. 1997 February; 50(2): 148-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9155697

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In situ detection of Mycobacterium tuberculosis transcripts in human lung granulomas reveals differential gene expression in necrotic lesions. Author(s): Fenhalls G, Stevens L, Moses L, Bezuidenhout J, Betts JC, Helden Pv P, Lukey PT, Duncan K. Source: Infection and Immunity. 2002 November; 70(11): 6330-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12379712

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In situ expression of B7 and CD40 costimulatory molecules by normal human lung macrophages and epithelioid cells in tuberculoid granulomas. Author(s): Soler P, Boussaud V, Moreau J, Bergeron A, Bonnette P, Hance AJ, Tazi A. Source: Clinical and Experimental Immunology. 1999 May; 116(2): 332-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10337027

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In situ production of gamma interferon, interleukin-4, and tumor necrosis factor alpha mRNA in human lung tuberculous granulomas. Author(s): Fenhalls G, Wong A, Bezuidenhout J, van Helden P, Bardin P, Lukey PT. Source: Infection and Immunity. 2000 May; 68(5): 2827-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10768979

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Increased expression of vascular endothelial growth factor in pyogenic granulomas. Author(s): Bragado R, Bello E, Requena L, Renedo G, Texeiro E, Alvarez MV, Castilla MA, Caramelo C. Source: Acta Dermato-Venereologica. 1999 November; 79(6): 422-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10598753

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Inflammatory granulomas: evaluation with proton MRS. Author(s): Jayasundar R, Singh VP, Raghunathan P, Jain K, Banerji AK. Source: Nmr in Biomedicine. 1999 May; 12(3): 139-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10414948

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Interferon-gamma-producing cells and inducible nitric oxide synthase-producing cells in periapical granulomas. Author(s): Kabashima H, Nagata K, Maeda K, Iijima T. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1998 March; 27(3): 95-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9563799

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Interleukin-1 expression in inflammatory myopathies: evidence of marked immunoreactivity in sarcoid granulomas and muscle fibres showing ischaemic and regenerative changes. Author(s): Authier FJ, Mhiri C, Chazaud B, Christov C, Cherin P, Barlovatz-Meimon G, Gherardi RK. Source: Neuropathology and Applied Neurobiology. 1997 April; 23(2): 132-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9160898

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Intraoperative cytologic diagnosis of granulomas: a retrospective study of 156 cases. Author(s): Eltoum IA, Tabbara S. Source: Diagnostic Cytopathology. 1998 January; 18(1): 62-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9451560

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Involvement of substance P, mast cells, TNF-alpha and ICAM-1 in the infiltration of inflammatory cells in human periapical granulomas. Author(s): Kabashima H, Nagata K, Maeda K, Iijima T. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2002 March; 31(3): 175-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903825

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Is silver nitrate the best agent for management of umbilical granulomas? Author(s): Daniels J. Source: Archives of Disease in Childhood. 2001 November; 85(5): 432. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035816

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Keratin granulomas in irradiated squamous cell carcinoma of various sites. Author(s): Safall H, Azar HA. Source: Cancer Research. 1966 March; 26(3): 500-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5930697

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Keratin granulomas in squamous cell carcinomas treated by irradiation. Author(s): Reddy CR, Rajakumari K, Jayasimha P. Source: Indian Journal of Cancer. 1975 September; 12(3): 327-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1193665

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Langerhans' cell histiocytosis in association with periapical granulomas and cysts. Author(s): Pringle GA, Daley TD, Veinot LA, Wysocki GP. Source: Oral Surg Oral Med Oral Pathol. 1992 August; 74(2): 186-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1508527

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Laryngeal granulomas of the false vocal fold. Author(s): Sataloff RT, Spiegel JR, Hawkshaw MJ. Source: Ear, Nose, & Throat Journal. 1995 October; 74(10): 687. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8529545

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Laryngeal pyogenic granulomas do not express oestrogen or progesterone receptors. Author(s): Marrinan MS, Myssiorek D, Fuchs A, Wasserman P. Source: The Journal of Laryngology and Otology. 2001 October; 115(10): 798-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11667991

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Letter: Granulomas in pulmonary veno-occlusive disease. Author(s): Olsen GN. Source: Chest. 1976 January; 69(1): 138. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1244280

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Leuprorelin acetate granulomas: recurrent subcutaneous nodules mimicking metastatic deposits at injection sites. Author(s): Whitaker IS, Fazel MZ, Joshi HB, Moseley RP, Turner WH. Source: Bju International. 2002 August; 90(3): 350. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12133078

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Leuprorelin acetate granulomas: recurrent subcutaneous nodules mimicking metastatic deposits at injections sites. Author(s): Saxby M. Source: Bju International. 2003 January; 91(1): 125. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614269

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Liver adenoma with granulomas. The appearance of granulomas in oral contraceptive-related hepatocellular adenoma and in the surrounding nontumorous liver. Author(s): Malatjalian DA, Graham CH. Source: Archives of Pathology & Laboratory Medicine. 1982 May; 106(5): 244-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6896136

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Liver adenomatosis with granulomas in two patients on long-term oral contraceptives. Author(s): Le Bail B, Jouhanole H, Deugnier Y, Salame G, Pellegrin JL, Saric J, Balabaud C, Bioulac-Sage P. Source: The American Journal of Surgical Pathology. 1992 October; 16(10): 982-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1357995

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Liver and bone marrow granulomas in Q fever. Author(s): Voigt JJ, Delsol G, Fabre J. Source: Gastroenterology. 1983 April; 84(4): 887-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6826001

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Liver granulomas and allopurinol. Author(s): Medline A, Cohen LB, Tobe BA, Sellers EM. Source: British Medical Journal. 1978 May 20; 1(6123): 1320-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=647256

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Liver granulomas in schistosomiasis: mast cell-dependent induction of SCF expression in hepatic stellate cells is mediated by TNF-alpha. Author(s): Brito JM, Borojevic R. Source: Journal of Leukocyte Biology. 1997 September; 62(3): 389-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9307079

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Liver granulomas: a possible paraneoplastic manifestation of hypernephroma. Author(s): Chagnac A, Gal R, Kimche D, Zevin D, Machtey I, Levi J. Source: The American Journal of Gastroenterology. 1985 December; 80(12): 989-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4073005

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Localisation of mycobacterial DNA and mRNA in human tuberculous granulomas. Author(s): Fenhalls G, Stevens-Muller L, Warren R, Carroll N, Bezuidenhout J, Van Helden P, Bardin P. Source: Journal of Microbiological Methods. 2002 October; 51(2): 197-208. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12133612

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Localization of angiotensin converting enzyme (ACE) in granulomas of sarcoidosis cutaneous lesions. Author(s): Takemura S, Fujioka A, Yasui Y, Baba S, Suzuki H. Source: The Journal of Dermatology. 1987 April; 14(2): 122-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3038979

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Localized eosinophilic gastroenteritis with necrotizing granulomas presenting as acute abdomen. Author(s): Fraile G, Rodriguez-Garcia JL, Beni-Perez R, Redondo C. Source: Postgraduate Medical Journal. 1994 July; 70(825): 510-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7937432

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Longterm survival in acute rhinocerebral mucormycosis with giant cell arteritis and foreign body granulomas. Author(s): Castillo L, Hofman V, Betis F, Piche M, Roger PM, Santini J, Hofman P. Source: Pathology, Research and Practice. 2001; 197(3): 199-203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11314785

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Low-grade B-cell lymphoma and concomitant extensive sarcoidlike granulomas: a case report and review of the literature. Author(s): Dunphy CH, Panella MJ, Grosso LE. Source: Archives of Pathology & Laboratory Medicine. 2000 January; 124(1): 152-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10629150

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Lung metastases from synovial sarcoma simulating granulomas. Author(s): Zollikofer C, Castaneda-Zuniga W, Stenlund R, Sibley R. Source: Ajr. American Journal of Roentgenology. 1980 July; 135(1): 161-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6249104

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Lymphocyte subsets in granulomas of human tuberculosis: an in situ immunofluorescence study using monoclonal antibodies. Author(s): Randhawa PS. Source: Pathology. 1990 July; 22(3): 153-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2243727

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Lysinuric protein intolerance with chronic interstitial lung disease and pulmonary cholesterol granulomas at onset. Author(s): Kerem E, Elpelg ON, Shalev RS, Rosenman E, Bar Ziv Y, Branski D. Source: The Journal of Pediatrics. 1993 August; 123(2): 275-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8345427

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Macronodular hepatic granulomas due to visceral leishmaniasis in an AIDS patient: imaging findings. Author(s): Canalias J, Falco J, Martin J, Jurado I. Source: Journal of Computer Assisted Tomography. 1997 July-August; 21(4): 677-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9216784

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Magnetic resonance imaging appearance of foreign body granulomas of the upper arms. Author(s): Varma DG, Ro JY, Guo SQ, Moulopoulos LA. Source: Clinical Imaging. 1994 January-March; 18(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8180859

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Management of cholesterol granulomas of the petrous apex based on clinical and radiologic evaluation. Author(s): Mosnier I, Cyna-Gorse F, Grayeli AB, Fraysse B, Martin C, Robier A, Gardini B, Chelikh L, Sterkers O. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2002 July; 23(4): 522-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12170156

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Manganese superoxide dismutase, but not CuZn superoxide dismutase, is highly expressed in the granulomas of pulmonary sarcoidosis and extrinsic allergic alveolitis. Author(s): Lakari E, Paakko P, Kinnula VL. Source: American Journal of Respiratory and Critical Care Medicine. 1998 August; 158(2): 589-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9700139

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Meningeal granulomas: sarcoidosis or tuberculosis? Differentiation can be difficult. Author(s): Jarman PR. Source: Bmj (Clinical Research Ed.). 1995 February 25; 310(6978): 517-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7888899

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Minocycline for the treatment of cutaneous silicone granulomas. Author(s): Senet P, Bachelez H, Ollivaud L, Vignon-Pennamen D, Dubertret L. Source: The British Journal of Dermatology. 1999 May; 140(5): 985-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10354059

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Minocycline-induced systemic adverse reaction with liver and bone marrow granulomas and Sezary-like cells. Author(s): Kettaneh A, Fain O, Ziol M, Lejeune F, Eclache-Saudreau V, Biaggi A, Guettier-Bouttier C, Thomas M. Source: The American Journal of Medicine. 2000 March; 108(4): 353-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11014736

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Misdiagnosis of cancer due to multiple glove powder granulomas. Author(s): Giercksky KE. Source: Eur J Surg Suppl. 1997; (579): 11-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9195176

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Mucosa-associated lymphoid tissue lymphoma coexisting with epithelioid granulomas in the stomach of a patient with systemic sarcoidosis. Author(s): Fukuda T, Sato K, Tachikawa S, Ohnuki K, Ohtani H, Suzuki T. Source: Pathology International. 1997 December; 47(12): 870-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9503470

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Multiple and synchronous peripheral giant cell granulomas of the gums. Author(s): Junquera LM, Lupi E, Lombardia E, Fresno MF. Source: The Annals of Otology, Rhinology, and Laryngology. 2002 August; 111(8): 751-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12184600

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Multiple glove powder granulomas masquerading as peritoneal carcinomatosis. Author(s): Giercksky KE, Qvist H, Giercksky TC, Warloe T, Nesland JM. Source: Journal of the American College of Surgeons. 1994 September; 179(3): 299-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8069426

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Multiple palisading granulomas in the scalp of an infant: a case report. Author(s): Hata N, Inamura T, Imayama S, Morioka T, Nishio S, Miyazono M, Fukui M, Iwaki T. Source: Surgical Neurology. 2001 December; 56(6): 396-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11755979

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Multiple plasma cell granulomas of the central nervous system: case report. Author(s): Hsiang J, Moorhouse D, Barba D. Source: Neurosurgery. 1994 October; 35(4): 744-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7808621

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Multiple pyogenic granulomas in sigmoid colon. Author(s): Chen TC, Lien JM, Ng KF, Lin CJ, Ho YP, Chen CM. Source: Gastrointestinal Endoscopy. 1999 February; 49(2): 257-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9925711

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Multiple recurrent laryngeal granulomas. Author(s): Sataloff RT, Sataloff DM, Hawkshaw M. Source: Ear, Nose, & Throat Journal. 1997 May; 76(5): 292. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9170709

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Myocarditis and subcutaneous granulomas in a patient with Crohn's disease of the colon. Author(s): Weiss N, Rademacher A, Zoller WG, Schlondorff D. Source: The American Journal of Medicine. 1995 October; 99(4): 434-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7573101

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Necrobiosis lipoidica and silicotic granulomas on Muller's phlebectomy scars. Author(s): Vion B, Burri G, Ramelet AA. Source: Dermatology (Basel, Switzerland). 1997; 194(1): 55-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9031793

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Necrobiotic granulomas of the urogenital system. Author(s): Slater D, Henry L. Source: Journal of Clinical Pathology. 1995 July; 48(7): 690. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7560190

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Necrobiotic granulomas of the urogenital system. Author(s): Aqel NM. Source: Journal of Clinical Pathology. 1995 February; 48(2): 185. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7745122

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Necrobiotic palisading granulomas associated with face cream injections. Author(s): Mir RN. Source: Plastic and Reconstructive Surgery. 1996 April; 97(4): 871-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8628791

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Necrobiotic palisading suture granulomas involving bone and joint: report of two cases. Author(s): Marcus VA, Roy I, Sullivan JD, Sutton JR. Source: The American Journal of Surgical Pathology. 1997 May; 21(5): 563-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9158681

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Necrotising granulomas of the uterine corpus. Author(s): Smith JH, Kennedy A, Sharp F, Reid PC, Thurrell W. Source: Journal of Clinical Pathology. 1994 April; 47(4): 381-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8027387

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Necrotizing granulomas in B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma. Author(s): Blanco M, Ratzan J, Cabello-Inchausti B, Fernandes L. Source: Annals of Diagnostic Pathology. 2002 August; 6(4): 216-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12170452

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Nerve granulomas and vasculitis in sarcoid peripheral neuropathy: a clinicopathological study of 11 patients. Author(s): Said G, Lacroix C, Plante-Bordeneuve V, Le Page L, Pico F, Presles O, Senant J, Remy P, Rondepierre P, Mallecourt J. Source: Brain; a Journal of Neurology. 2002 February; 125(Pt 2): 264-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11844727

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Non-caseating granulomas as a cause of ischaemic retinal vasculitis. Author(s): Palmer HE, Stanford MR, McCartney AC, Graham EM. Source: The British Journal of Ophthalmology. 1997 November; 81(11): 1018-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9505832

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Non-ossifying fibromas and giant cell reparative granulomas in a child with ocularectodermal syndrome. Author(s): Toriello HV, Bultman R, Panek RW, Hammers Y, Kohut G, Droste P, Freyer DR. Source: Clinical Dysmorphology. 1999 October; 8(4): 265-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10532175

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Occupational skin granulomas. Author(s): Bigardi AS, Pigatto PD, Moroni P. Source: Clinics in Dermatology. 1992 April-June; 10(2): 219-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1393958

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On the isolation of infectious agents from granulomas of patients with sarcoid. Author(s): Bowman BU, Koehler RM, Kubina G. Source: Am Rev Respir Dis. 1973 March; 107(3): 467-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4690495

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Operative treatment of intracranial epidermoid cysts and cholesterol granulomas: report of 21 cases. Author(s): Altschuler EM, Jungreis CA, Sekhar LN, Jannetta PJ, Sheptak PE. Source: Neurosurgery. 1990 April; 26(4): 606-13; Discussion 614. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2330082

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Oral giant pyogenic granulomas associated with facial skin hemangiomas (SturgeWeber syndrome). Author(s): Ilgenli T, Canda T, Canda S, Unal T, Baylas H. Source: Periodontal Clin Investig. 1999; 21(2): 28-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10860035

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Oral pyogenic granulomas. Author(s): Butler EJ, Macintyre DR. Source: Dent Update. 1991 June; 18(5): 194-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1884869

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Origin of malignant centrofacial granulomas: surface markers and gene rearrangement of malignant cells. Author(s): Cabane J, Raphael M, Lamas G, Mossalayi D, Dubois A, Chomette G, Godeau P, Marty-Double C, Rossi JF. Source: The Laryngoscope. 1991 September; 101(9): 998-1001. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1886450

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Orofacial granulomas after injection of cosmetic fillers. Histopathologic and clinical study of 11 cases. Author(s): Lombardi T, Samson J, Plantier F, Husson C, Kuffer R. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 2004 February; 33(2): 115-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720198

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Osteopontin is associated with T cells in sarcoid granulomas and has T cell adhesive and cytokine-like properties in vitro. Author(s): O'Regan AW, Chupp GL, Lowry JA, Goetschkes M, Mulligan N, Berman JS. Source: Journal of Immunology (Baltimore, Md. : 1950). 1999 January 15; 162(2): 1024-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9916729

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Osteopontin is strongly expressed by histiocytes in granulomas of diverse etiology. Author(s): Carlson I, Tognazzi K, Manseau EJ, Dvorak HF, Brown LF. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1997 July; 77(1): 103-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9251683

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Ovarian granulomas: a report of 32 cases. Author(s): McCluggage WG, Allen DC. Source: Journal of Clinical Pathology. 1997 April; 50(4): 324-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9215150

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Pathogenetic roles of angiogenic factors in pyogenic granulomas in pregnancy are modulated by female sex hormones. Author(s): Yuan K, Wing LY, Lin MT. Source: J Periodontol. 2002 July; 73(7): 701-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12146528

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Pathologic quiz case. Supraglottic granulomas in a young Central American Man. Author(s): Omeroglu A, Weisenberg E, Baim HM, Rhone DP. Source: Archives of Pathology & Laboratory Medicine. 2001 January; 125(1): 157-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11151073

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PCR detection of Mycobacterium paratuberculosis in Crohn's disease granulomas isolated by laser capture microdissection. Author(s): Ryan P, Bennett MW, Aarons S, Lee G, Collins JK, O'Sullivan GC, O'Connell J, Shanahan F. Source: Gut. 2002 November; 51(5): 665-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377804

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Petrous apex cholesterol granulomas: evolution and management. Author(s): Eisenberg MB, Haddad G, Al-Mefty O. Source: Journal of Neurosurgery. 1997 May; 86(5): 822-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9126898

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Petrous apex granulomas: CT and MR imaging. Author(s): Hentschel S, Durity F. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2002 May; 29(2): 169-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035839

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Postoperative granulomas of the endometrium: histological features after endometrial ablation. Author(s): Silvernagel SW, Harshbarger KE, Shevlin DW. Source: Annals of Diagnostic Pathology. 1997 December; 1(2): 82-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9869829

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Presence of granulomas is associated with recurrence after surgery for Crohn's disease: experience of a surgical unit. Author(s): Anseline PF, Wlodarczyk J, Murugasu R. Source: The British Journal of Surgery. 1997 January; 84(1): 78-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9043461

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Psychological profiles of patients with laryngeal contact granulomas. Author(s): Kiese-Himmel C, Pralle L, Kruse E. Source: European Archives of Oto-Rhino-Laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (Eufos) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 1998; 255(6): 296-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9693925

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Pulmonary cholesterol granulomas in patients with pulmonary artery hypertension: chest radiographic and CT findings. Author(s): Nolan RL, McAdams HP, Sporn TA, Roggli VL, Tapson VF, Goodman PC. Source: Ajr. American Journal of Roentgenology. 1999 May; 172(5): 1317-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10227509

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Pulmonary miliary tuberculosis with multiple intracerebral tuberculous granulomas-report of two cases. Author(s): Muin IA, Zurin AR. Source: British Journal of Neurosurgery. 1998 December; 12(6): 585-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10070474

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Quantitation of hepatic granulomas and epithelioid cells in primary biliary cirrhosis. Author(s): Nakanuma Y, Ohta G. Source: Hepatology (Baltimore, Md.). 1983 May-June; 3(3): 423-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6840688

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Rapid detection of mycobacteria in inflammatory necrotizing granulomas from formalin-fixed, paraffin-embedded tissue by PCR in clinically high-risk patients with acid-fast stain and culture-negative tissue biopsies. Author(s): Hardman WJ, Benian GM, Howard T, McGowan JE Jr, Metchock B, Murtagh JJ. Source: American Journal of Clinical Pathology. 1996 September; 106(3): 384-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8816599

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Re: Transrectal ultrasound appearance of prostatic granulomas secondary to bacillus Calmette-Guerin instillation. Author(s): Shandera KC. Source: The Journal of Urology. 1998 April; 159(4): 1313-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9507874

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Re: Use of tissue expanders in reconstruction after excision of multiple large silicone granulomas. Author(s): Boskovic DM. Source: Annals of Plastic Surgery. 1993 October; 31(4): 379. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8239442

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Recurrent laryngeal granulomas. Author(s): Sataloff RT, Spiegel JR, Baroody MM. Source: Ear, Nose, & Throat Journal. 1995 August; 74(8): 514. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7555866

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Relation of granulomas to lymphatic vessels in Crohn's disease. Author(s): Mooney EE, Walker J, Hourihane DO. Source: Journal of Clinical Pathology. 1995 April; 48(4): 335-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7615853

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Renal granulomas in systemic vasculitis. EC/BCR Project for ANCA-Assay Standardization. Author(s): Bajema IM, Hagen EC, Ferrario F, Waldherr R, Noel LH, Hermans J, van der Woude FJ, Bruijn JA. Source: Clinical Nephrology. 1997 July; 48(1): 16-21. Erratum In: Clin Nephrol 1998 April; 49(4): 272. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9247773

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Resection of liver granulomas under a diagnosis of metastases from breast cancer. Author(s): Matsuo K, Sugawara Y, Yamamoto J, Yamasaki S, Shimada K, Kosuge T, Sakamoto M, Takayama T, Makuuchi M. Source: Abdominal Imaging. 2000 May-June; 25(3): 259-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10823446

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Restraining mycobacteria: role of granulomas in mycobacterial infections. Author(s): Saunders BM, Cooper AM. Source: Immunology and Cell Biology. 2000 August; 78(4): 334-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10947857

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Rheumatoid arthritis complicated by pachy- and leptomeningeal rheumatoid nodulelike granulomas and systemic vasculitis. Author(s): Kamio N, Kuramochi S, Wang RJ, Hirose S, Hosoda Y. Source: Pathology International. 1996 July; 46(7): 526-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8870010

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Role of the HLA-DP gene in susceptibility to lung granulomas. Author(s): Saltini C, Sorrentino R, Richeldi L, Luisetti M, Bisetti A. Source: Sarcoidosis. 1993 September; 10(2): 171-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8140323

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Silicon granulomas and dermatomyositis-like changes associated with chronic eyelid edema after silicone breast implant. Author(s): Meyer DR, Bui HX, Carlson JA, Ratliff CD, Guevarra MC, DelRosario AD, Ross JS, Mihm M Jr. Source: Ophthalmic Plastic and Reconstructive Surgery. 1998 May; 14(3): 182-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9612809

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Skin granulomas after liver transplantation: unusual presentation of recurrent primary biliary cirrhosis. Author(s): Armali Z, Bassan L, Bergman R, Baruch Y. Source: Transplantation Proceedings. 2000 June; 32(4): 717. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10856557

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Spermatic granulomas resembling testicular neoplasia. Author(s): Divani S, Alexopoulou E, Demetriadis I. Source: Cytopathology : Official Journal of the British Society for Clinical Cytology. 1998 October; 9(5): 354-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9800137

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Spinal cord compression by catheter granulomas in high-dose intrathecal morphine therapy: case report. Author(s): Langsam A. Source: Neurosurgery. 1999 March; 44(3): 689-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10069613

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Spinal cord compression by catheter granulomas in high-dose intrathecal morphine therapy: case report. Author(s): Cabbell KL, Taren JA, Sagher O. Source: Neurosurgery. 1998 May; 42(5): 1176-80; Discussion 1180-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9588567

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Study of the expression of CD68+ macrophages and CD8+ T cells in human granulomas and periapical cysts. Author(s): Rodini CO, Lara VS. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001 August; 92(2): 221-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11505271

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Surgical management of petrous apex cholesterol granulomas. Author(s): Brackmann DE, Toh EH. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2002 July; 23(4): 529-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12170157

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Suture granulomas: sonography enables a correct preoperative diagnosis. Author(s): Rettenbacher T, Macheiner P, Hollerweger A, Gritzmann N, Weismann C, Todoroff B. Source: Ultrasound in Medicine & Biology. 2001 March; 27(3): 343-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11369119

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Systemic sarcoidosis presenting with multiple tattoo granulomas and an extra-tattoo cutaneous granuloma. Author(s): Papageorgiou PP, Hongcharu W, Chu AC. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 1999 January; 12(1): 51-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10188151

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The calcified intracorporeal vacuole: an aid to the pathological diagnosis of solitary cerebral cysticercus granulomas. Author(s): Pandian JD. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2001 November; 71(5): 708. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11688496

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The calcified intracorporeal vacuole: an aid to the pathological diagnosis of solitary cerebral cysticercus granulomas. Author(s): Chacko G, Rajshekhar V, Chandy MJ, Chandi SM. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2000 October; 69(4): 525-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10990517

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The development of granulomas in schistosomiasis: genetic backgrounds, regulatory pathways, and specific egg antigen responses that influence the magnitude of disease. Author(s): Stadecker MJ. Source: Microbes and Infection / Institut Pasteur. 1999 June; 1(7): 505-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10603566

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The etiology of hepatic granulomas. Author(s): Mert A, Ozaras R, Bilir M, Tahan V, Cetinkaya A, Yirmibescik S, Ozbay G, Senturk H. Source: Journal of Clinical Gastroenterology. 2001 March; 32(3): 275-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11246365

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The presence of chemokine receptor (CCR5, CXCR3, CCR3)-positive cells and chemokine (MCP1, MIP-1alpha, MIP-1beta, IP-10)-positive cells in human periapical granulomas. Author(s): Kabashima H, Yoneda M, Nagata K, Hirofuji T, Ishihara Y, Yamashita M, Maeda K. Source: Cytokine. 2001 October 21; 16(2): 62-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11683586

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The role of ultrasound in the diagnosis of stitch granulomas following paediatric herniotomy. Author(s): Nagar H, Kessler A, Graif M. Source: Pediatric Radiology. 1999 November; 29(11): 803-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10552055

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Treatment of laryngeal contact ulcers and granulomas: a 12-year retrospective analysis. Author(s): Emami AJ, Morrison M, Rammage L, Bosch D. Source: Journal of Voice : Official Journal of the Voice Foundation. 1999 December; 13(4): 612-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10622526

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Tuberculoid granulomas and cervical granulomatous lymphadenitis. Author(s): Svebis M, Cserni G. Source: Histopathology. 2000 November; 37(5): 478-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11119141

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Tuberculous choroidal granulomas in a patient with systemic lupus erythematosus. A case report. Author(s): Wang JC, Chuah GC, Yap EY. Source: International Ophthalmology. 2001; 24(2): 107-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12201345

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Tuberculous granulomas in childhood tuberculous meningitis: radiological features and course. Author(s): Ravenscroft A, Schoeman JF, Donald PR. Source: Journal of Tropical Pediatrics. 2001 February; 47(1): 5-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11245351

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Ultrastructural analysis of periapical granulomas. Author(s): Piattelli A, Artese L. Source: Bull Group Int Rech Sci Stomatol Odontol. 1994 March-June; 37(1-2): 27-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7994157

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Ultrastructural characteristics of macrophages in dermal leprosy granulomas: macrophages in leprosy granulomas. Author(s): Kumar V, Narayanan RB, Malaviya GN. Source: Nippon Rai Gakkai Zasshi. 1989 July-September; 58(3): 185-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2642167

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Ultrastructural heterogeneity of epithelioid cells in cutaneous organized granulomas of diverse etiology. Author(s): Epstein WL. Source: Archives of Dermatology. 1991 June; 127(6): 821-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2036027

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Umbilical granulomas: a randomised controlled trial. Author(s): Daniels J, Craig F, Wajed R, Meates M. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2003 May; 88(3): F257. Erratum In: Arch Dis Child Fetal Neonatal Ed. 2003 September; 88(5): F446. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12719409

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Unexplained bone marrow granulomas: is amiodarone the culprit? A report of 2 cases. Author(s): Mukhopadhyay S, Mukhopadhyay S, Abraham NZ Jr, Jones LA, Howard L, Gajra A. Source: American Journal of Hematology. 2004 February; 75(2): 110-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755379

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Unusual development of granulomas on the healing surface of burn wounds associated with MRSA infections. Author(s): Gang RK, Bajec J, Krishna J, Sanyal SC. Source: Burns : Journal of the International Society for Burn Injuries. 1996 February; 22(1): 57-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8719319

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Unusual particles and crystals in Crohn's disease granulomas. Author(s): Roge J, Fabre M, Levillain P, Dubois P. Source: Lancet. 1991 February 23; 337(8739): 502-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1671513

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Use of tissue expanders in reconstruction after excision of multiple large silicone granulomas. Author(s): Wilke CP, Woods JE. Source: Annals of Plastic Surgery. 1993 April; 30(4): 367-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8512296

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Uterine granulomas: clinical and pathologic features. Author(s): Almoujahed MO, Briski LE, Prysak M, Johnson LB, Khatib R. Source: American Journal of Clinical Pathology. 2002 May; 117(5): 771-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12090427

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Uterine granulomas: tuberculosis, an important cause. Author(s): Mishra K, Wadhwa N. Source: American Journal of Clinical Pathology. 2002 December; 118(6): 966-7; Author Reply 967. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12472289

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Vaccination granulomas and aluminium allergy: course and prognostic factors. Author(s): Kaaber K, Nielsen AO, Veien NK. Source: Contact Dermatitis. 1992 May; 26(5): 304-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1395591

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Value of gallium imaging in the evaluation of tattoo granulomas due to sarcoidosis. Author(s): Colp CR, Goldfarb R, Ongseng F. Source: Chest. 1991 December; 100(6): 1737-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1959427

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Variably acid-fast bacteria in a rare case of coexistent malignant lymphoma and cutaneous sarcoid-like granulomas. Author(s): Cantwell AR Jr. Source: International Journal of Dermatology. 1982 March; 21(2): 99-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7068309

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Viral glycoproteins in herpesviridae granulomas. Author(s): Nikkels AF, Debrus S, Delvenne P, Sadzot-Delvaux C, Piette J, Rentier B, Pierard GE. Source: The American Journal of Dermatopathology. 1994 December; 16(6): 588-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7864296

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Visceral eosinophilic granulomas. Author(s): Salfelder K, De Liscano TR, De Mendelovici M. Source: Beitr Pathol. 1973 September; 149(4): 420-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4771311

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Vocal cord granulomas. Author(s): Benjamin B, Croxson G. Source: The Annals of Otology, Rhinology, and Laryngology. 1985 NovemberDecember; 94(6 Pt 1): 538-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4073728

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Warthin's tumor with multiple sarcoid-like granulomas: a case report. Author(s): To EW, Tsang WM, Leung CY, Lee KL. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2002 May; 60(5): 585-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11988942

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What makes granulomas tick? Author(s): James DG. Source: Thorax. 1991 October; 46(10): 734-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1750022

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Widespread foreign-body granulomas and elevated serum angiotensin-converting enzyme. Author(s): Pucevich MV, Rosenberg EW, Bale GF, Terzakis JA. Source: Archives of Dermatology. 1983 March; 119(3): 229-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6297413

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Ziehl-Neelsen staining and polymerase chain reaction study of tissue from tuberculous granulomas. Author(s): Mert A, Ozaras R, Bilir M, Tabak F, Aki H, Ozturk R. Source: Respirology (Carlton, Vic.). 2003 December; 8(4): 548. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629660

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Zinc sulfate therapy for vocal cord granulomas. Author(s): Marshak A, Marshak G. Source: The Journal of Laryngology and Otology. 1973 June; 87(6): 573-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4718445

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Zirconium granuloma resulting from an aluminum zirconium complex: a previously unrecognized agent in the development of hypersensitivity granulomas. Author(s): Skelton HG 3rd, Smith KJ, Johnson FB, Cooper CR, Tyler WF, Lupton GP. Source: Journal of the American Academy of Dermatology. 1993 May; 28(5 Pt 2): 874-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8491884

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CHAPTER 2. NUTRITION AND GRANULOMAS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and granulomas.

Finding Nutrition Studies on Granulomas 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 “granulomas” (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 information is typical of that found when using the “Full IBIDS Database” to search for “granulomas” (or a synonym): •

Central giant cell granulomas of the jaws regress with calcitonin therapy. Author(s): Joint Department of Maxillofacial Surgery and Oral Medicine, Eastman Dental Hospital, London. Source: Harris, M Br-J-Oral-Maxillofac-Surg. 1993 April; 31(2): 89-94 0266-4356

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Cholesterol granulomas in mice deficient in apolipoprotein E. Author(s): Johns Hopkins University, School of Medicine, 459 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA. Source: Owiny, J R Strandberg, J D Contemp-Top-Lab-Anim-Sci. 2000 November; 39(6): 57-8 1060-0558

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Comparison of lipid accumulation and metabolism in carrageenan-induced granulomas to aorta and blood monocytes of normal and cholesterol-fed rabbits. Author(s): Metabolic Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001. Source: Bell, F P Schaub, R G Exp-Mol-Pathol. 1989 June; 50(3): 327-36 0014-4800

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Effect of chronic treatment with a purified flavonoid fraction on inflammatory granuloma in the rat. Study of prostaglandin E2 and F2 alpha and thromboxane B2 release and histological changes. Author(s): INSERM, U 58, Montpellier, France. Source: Damon, M Flandre, O Michel, F Perdrix, L Labrid, C Crastes de Paulet, A Arzneimittelforschung. 1987 October; 37(10): 1149-53 0004-4172

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Effect of policosanol on foam-cell formation in carrageenan-induced granulomas in rats. Author(s): Laboratory of Histology, National Center for Scientific Research, La Habana, Cuba. Source: Noa, M de la Rosa, M C Mas, R J-Pharm-Pharmacol. 1996 March; 48(3): 306-9 0022-3573

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Granuloma formation by artificial microparticles in vitro. Macrophages and monokines play a critical role in granuloma formation. Author(s): First Department of Internal Medicine and Showa University School of Medicine, Tokyo, Japan. Source: Shikama, Y Kobayashi, K Kasahara, K Kaga, S Hashimoto, M Yoneya, I Hosoda, S Soejima, K Ide, H Takahashi, T Am-J-Pathol. 1989 June; 134(6): 1189-99 0002-9440

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In vivo administration of mycobacterial cord factor (Trehalose 6, 6'-dimycolate) can induce lung and liver granulomas and thymic atrophy in rabbits. Author(s): Department of Host Defense, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan. [email protected] Source: Hamasaki, N Isowa, K Kamada, K Terano, Y Matsumoto, T Arakawa, T Kobayashi, K Yano, I Infect-Immun. 2000 June; 68(6): 3704-9 0019-9567

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Influence of dietary n-6 and n-3 lipids upon the development of pulmonary granulomas induced by Schistosoma mansoni eggs. Author(s): Departamento de Parasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil. Source: Lima, S F Ribeiro, R A Arantes, R Coelho, P M Vieira, L Q Mem-Inst-OswaldoCruz. 1998; 93 Suppl 1197-8 0074-0276

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Influence of hypercholesterolemia and cholesterol accumulation on rabbit carrageenan granuloma macrophage activation. Author(s): Department of Pathology, University of Texas Health Science Center, San Antonio 78284. Source: Kelley, J L Suenram, C A Rozek, M M Schwartz, C J Am-J-Pathol. 1988 June; 131(3): 539-46 0002-9440

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Influence of the acyl-CoA: cholesterol O-acyltransferase inhibitor, CL 277082, on cholesteryl ester accumulation in rabbit macrophage-rich granulomas and hepatic tissue. Author(s): Department of Pathology, University of Texas Health Science Center, San Antonio 78284. Source: Kelley, J L Suenram, C A Rozek, M M Schaffer, S A Schwartz, C J BiochimBiophys-Acta. 1988 May 2; 960(1): 83-90 0006-3002

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Interactions between adherent mononuclear cells and lymphocytes from granulomas of mice with schistosomiasis mansoni. Author(s): Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201. Source: Elliott, D E Ragheb, S Wellhausen, S R Boros, D L Infect-Immun. 1990 June; 58(6): 1577-83 0019-9567

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Linoleic and dihomo-gamma-linolenic acids modulate granuloma growth and granuloma macrophage eicosanoid release. Source: Elliott, G R Adolfs, M J Van Batenburg, M Bonta, I L Eur-J-Pharmacol. 1986 May 27; 124(3): 325-9 0014-2999

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Macrophage-specific expression of class A scavenger receptors enhances granuloma formation in the absence of increased lipid deposition. Author(s): Gill Heart Institute, Atherosclerosis Research Group, Division of Cardiovascular Medicine, University of Kentucky, L543 KY Clinic, Lexington, KY 405360284, USA. [email protected] Source: Daugherty, A Kosswig, N Cornicelli, J A Whitman, S C Wolle, S Rateri, D L JLipid-Res. 2001 July; 42(7): 1049-55 0022-2275

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Modulation of granuloma formation in vitro by endogenous mediators. Author(s): First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan. Source: Sato, I Y Kobayashi, K Yamagata, N Shikama, Y Kasama, T Kasahara, K Takahashi, T Immunopharmacology. 1991 Mar-April; 21(2): 73-82 0162-3109

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Monokine production by hypersensitivity (Schistosoma mansoni egg) and foreign body (Sephadex bead)-type granuloma macrophages. Evidence for sequential production of IL-1 and tumor necrosis factor. Author(s): Department of Pathology, Veterans Administration Medical Center, Ann Arbor, MI 48105. Source: Chensue, S W Otterness, I G Higashi, G I Forsch, C S Kunkel, S L J-Immunol. 1989 February 15; 142(4): 1281-6 0022-1767

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Nodular tertiary syphilis mimicking granuloma annulare. Author(s): Division of Dermatology, The Ohio State University, Columbus 43210, USA. Source: Wu, S J Nguyen, E Q Nielsen, T A Pellegrini, A E J-Am-Acad-Dermatol. 2000 February; 42(2 Pt 2): 378-80 0190-9622

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Nonparenchymal liver cells and granulomas during lamprey biliary atresia. Source: Youson, J H Sargent, P A Yamamoto, K Ogilvie, D Fisher, M M Am-J-Anat. 1987 June; 179(2): 155-68 0002-9106

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Pulmonary granulomas of guinea pigs induced by inhalation exposure of heat-treated BCG Pasteur, purified trehalose dimycolate and methyl ketomycolate. Author(s): Department of Molecular Pathology, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Kiyose, Tokyo. [email protected] Source: Sugawara, I Udagawa, T Hua, S C Reza Gholizadeh, M Otomo, K Saito, Y Yamada, H J-Med-Microbiol. 2002 February; 51(2): 131-7 0022-2615

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Rapid growth of giant cell granuloma in pregnancy treated with calcitonin. Author(s): Central Pathology Laboratory, St James's Hospital, Dublin, Ireland, United Kingdom. Source: O'Regan, E M Gibb, D H Odell, E W Oral-Surg-Oral-Med-Oral-Pathol-OralRadiol-Endod. 2001 November; 92(5): 532-8 1079-2104

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Relationship between induction of macrophage chemotactic factors and formation of granulomas caused by mycoloyl glycolipids from Rhodococcus ruber (Nocardia rubra). Author(s): Department of Bacteriology, Osaka City University Medical School. Source: Matsunaga, I Oka, S Fujiwara, N Yano, I J-Biochem-(Tokyo). 1996 September; 120(3): 663-70 0021-924X

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Squamous cell granulomas of the neck: histologic regression of metastatic squamous cell carcinoma following chemotherapy and/or radiotherapy. Author(s): Department of Pathology, Johns Hopkins Hospital, Baltimore, MD 212876417, USA. Source: Westra, W H Forastiere, A A Eisele, D W Lee, D J Head-Neck. 1998 September; 20(6): 515-21 1043-3074

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The production of macrophage aggregation factor (MAF) by in vitro cultured Schistosoma mansoni egg granulomas isolated from experimentally infected mice. Source: Giron, M E Rodriguez Acosta, F A Arch-Roum-Pathol-Exp-Microbiol. 1987 JanMarch; 46(1): 83-7 0004-0037

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Translocation of particle-laden alveolar macrophages and intra-alveolar granuloma formation in rats exposed to Ludox colloidal amorphous silica by inhalation. Author(s): Central Research and Development, Du Pont Company, Haskell Laboratory for Toxicology and Industrial Medicine, Newark, DE 19714. Source: Lee, K P Kelly, D P Toxicology. 1993 March 19; 77(3): 205-22 0300-483X

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Treatment of a granuloma caused by Halicephalobus gingivalis in a horse. Author(s): Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Canada. Source: Pearce, S G Boure, L P Taylor, J A Peregrine, A S J-Am-Vet-Med-Assoc. 2001 December 15; 219(12): 1735-8, 1708 0003-1488

Nutrition

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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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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND GRANULOMAS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to granulomas. 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 granulomas 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 “granulomas” (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 granulomas: •

Acupuncture granulomas. Author(s): Alani RM, Busam K. Source: Journal of the American Academy of Dermatology. 2001 December; 45(6 Suppl): S225-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11712067

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Anti-granuloma activity of Iraqi Withania somnifera. Author(s): al-Hindawi MK, al-Khafaji SH, Abdul-Nabi MH. Source: Journal of Ethnopharmacology. 1992 September; 37(2): 113-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1434685

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Bone marrow granulomas in acute myeloid leukaemia following interleukin 2 and lymphokine-activated killer cells. Author(s): O'Brien DV, Boon AP, Boughton BJ.

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Source: Histopathology. 1992 March; 20(3): 271-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1563716 •

Characterization of two dipeptidases purified from hepatic schistosome egg granulomas in mice. Leukotriene D4 hydrolases of granulomatous tissue. Author(s): Sato N, Ito Y, Iida T, Fukuyama K, Epstein WL. Source: The Biochemical Journal. 1992 June 15; 284 ( Pt 3): 885-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1622404

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Chronic inflammatory granuloma mimics clinical manifestations of lumbar spinal stenosis after acupuncture: a case report. Author(s): Ha KY, Kim YH. Source: Spine. 2003 June 1; 28(11): E217-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12782998

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Comparative study on the accelerative effect of “koushikon” and “nanshikon” and their constituents on proliferation of granuloma tissue in rats. Author(s): Ozaki Y, Ohno A, Abe K, Saito Y, Satake M. Source: Biological & Pharmaceutical Bulletin. 1993 July; 16(7): 683-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8401402

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Cutaneous granulomas as the first manifestation of Hodgkin's disease. Author(s): Macaya A, Servitje O, Moreno A, Peyri J. Source: European Journal of Dermatology : Ejd. 2003 May-June; 13(3): 299-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804995

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Effect of demineralization on stainability of human mast cells in normal periodontal membranes, apical granulomas and radicular cysts. Author(s): Mathiesen A. Source: Scand J Dent Res. 1973; 81(6): 441-51. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4128495

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Effects of the aqueous extract of Bridelia ferruginea stem bark on carrageenaninduced oedema and granuloma tissue formation in rats and mice. Author(s): Olajide OA, Makinde JM, Awe SO. Source: Journal of Ethnopharmacology. 1999 July; 66(1): 113-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10432217

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Elemental mercury-induced skin granuloma: a case report and review of the literature. Author(s): Bradberry SM, Feldman MA, Braithwaite RA, Shortland-Webb W, Vale JA.

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Source: Journal of Toxicology. Clinical Toxicology. 1996; 34(2): 209-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8618256 •

Eosinophilic foreign body granuloma after multiple self-administered bee stings. Author(s): Park JH, Kim JG, Cha SH, Park SD. Source: The British Journal of Dermatology. 1998 December; 139(6): 1102-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9990382

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Fine needle aspiration biopsy of a cutaneous relapse of lymphomatoid granulomatosis. A case report. Author(s): Vargas J, Arguelles M, Nevado M, de la Serna J, de Agustin P. Source: Acta Cytol. 1993 March-April; 37(2): 205-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8465642

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Gelatinase is the main matrix metalloproteinase involved in granuloma-induced cartilage degradation. Author(s): Trancart MM, Chalmeigne N, Girardot C, Zarpanelian C, Prigent D. Source: Int J Tissue React. 1992; 14(6): 287-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1339118

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Germinoma with a granulomatous reaction. Problems of differential diagnosis. Author(s): Konno S, Oka H, Utsuki S, Kondou K, Tanaka S, Fujii K, Yagishita S. Source: Clin Neuropathol. 2002 November-December; 21(6): 248-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12489672

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Granuloma annulare associated with Hodgkin's disease. Author(s): Setoyama M, Kerdel FA, Byrnes JJ, Kanzaki T. Source: International Journal of Dermatology. 1997 June; 36(6): 445-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9248891

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Granuloma annulare in a patient with malignant lymphoma. Author(s): Ono H, Yokozeki H, Katayama I, Nishioka K. Source: Dermatology (Basel, Switzerland). 1997; 195(1): 46-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9267737

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Granuloma maturation in the rat is advanced by the oral administration of Eucommia ulmoides OLIVER leaf. Author(s): Li Y, Metori K, Koike K, Kita F, Che QM, Sato T, Shirai W, Takahashi S. Source: Biological & Pharmaceutical Bulletin. 2000 January; 23(1): 60-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10706412

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Granulomatous gastroenteritis. Case report with comparison to idiopathic isolated granulomatous gastritis. Author(s): Zuckerman MJ, al-Samman M, Boman DA. Source: Digestive Diseases and Sciences. 1994 August; 39(8): 1649-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8050313

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Influence of dietary n-6 and n-3 lipids upon the development of pulmonary granulomas induced by Schistosoma mansoni eggs. Author(s): Lima SF, Ribeiro RA, Arantes R, Coelho PM, Vieira LQ. Source: Memorias Do Instituto Oswaldo Cruz. 1998; 93 Suppl 1: 197-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9921349

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Inhibition of protein kinases prevents lymphocyte activation by Schistosoma mansoni antigens and reduces in vitro [correction of in vivo] granuloma reaction. Author(s): Almeida CA, Romano-Silva MA, Goes AM. Source: Immunology Letters. 1998 July; 62(3): 137-43. Erratum In: Immunol Lett 1999 April 1; 67(2): 155. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9698111

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Interstitial and granulomatous drug reaction presenting as erythema nodosum-like lesions. Author(s): Lee MW, Choi JH, Sung KJ, Moon KC, Koh JK. Source: Acta Dermato-Venereologica. 2002; 82(6): 473-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12575862

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Isotretinoin in the treatment of granuloma annulare. Author(s): Looney M, Smith KM. Source: The Annals of Pharmacotherapy. 2004 March; 38(3): 494-7. Epub 2004 January 23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14970372

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Markedly elevated angiotensin converting enzyme in lymph nodes containing nonnecrotizing granulomas in sarcoidosis. Author(s): Silverstein E, Friedland J, Lyons HA, Gourin A. Source: Proceedings of the National Academy of Sciences of the United States of America. 1976 June; 73(6): 2137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6963

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Matrix metalloproteases are involved in granuloma-induced cartilage degradation. Author(s): Trancart MM, Chalmeigne N, Girardot C, Zarpanelian C, Prigent D. Source: Int J Tissue React. 1991; 13(4): 165-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1821411

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Medical management of eosinophilic granuloma of the cervical spine. Author(s): Levy EI, Scarrow A, Hamilton RC, Wollman MR, Fitz C, Pollack IF. Source: Pediatric Neurosurgery. 1999 September; 31(3): 159-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10708359

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Nasal natural killer cell lymphoma presenting as lethal midline granuloma. Author(s): Yamazaki M, Kakuta M, Takimoto R, Murayama N, Takamori K. Source: International Journal of Dermatology. 2000 December; 39(12): 931-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168665

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Pathology of liver granulomas in turkeys. Author(s): Arp LH, Robinson IM, Jensen AE. Source: Veterinary Pathology. 1983 January; 20(1): 80-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6849221

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Pulmonary granulomatosis caused by aspirated green tea. Author(s): Sakamoto O, Saita N, Yamasaki H, Tamanoi M, Ando M. Source: Chest. 1994 July; 106(1): 308-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8020300

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Pyogenic granuloma of the cornea induced by “snake oil”. Author(s): Proia AD, Small KW. Source: Cornea. 1994 May; 13(3): 284-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8033584

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Selective inhibition by magnosalin and magnoshinin, compounds from “Shin-i” (Flos magnoliae), of adjuvant-induced angiogenesis and granuloma formation in the mouse pouch. Author(s): Kimura M, Kobayashi S, Luo B, Kimura I. Source: Agents Actions Suppl. 1991; 32: 197-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1712537

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Selective inhibition by magnosalin and magnoshinin, compounds from 'shin-i' (Flos magnoliae), of adjuvant-induced angiogenesis and granuloma formation in the mouse pouch. Author(s): Kimura M, Kobayashi S, Luo B, Kimura I. Source: Int Arch Allergy Appl Immunol. 1990; 93(4): 365-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1713572

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Silica granuloma: scanning electron microscopy and energy dispersive X-ray microanalysis. Author(s): Chun SI, Cho SW.

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Source: The Journal of Dermatology. 1991 February; 18(2): 92-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1649207 •

Silicone granuloma on the entry points of acupuncture, venepuncture and surgical needles. Author(s): Yanagihara M, Fujii T, Wakamatu N, Ishizaki H, Takehara T, Nawate K. Source: Journal of Cutaneous Pathology. 2000 July; 27(6): 301-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10885407

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Squamous cell granulomas of the neck: histologic regression of metastatic squamous cell carcinoma following chemotherapy and/or radiotherapy. Author(s): Westra WH, Forastiere AA, Eisele DW, Lee DJ. Source: Head & Neck. 1998 September; 20(6): 515-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9702538

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Successful treatment of generalized granuloma annulare with polyethylene sheet bath PUVA. Author(s): Szegedi A, Begany A, Hunyadi J. Source: Acta Dermato-Venereologica. 1999 January; 79(1): 84-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10086870

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Suspected malignant lymphoma presenting with widespread granulomatous lesions in bones and lymph nodes and responding to combination chemotherapy. Author(s): Jensen MK, Pulczynski S, Johansen P. Source: Acta Haematologica. 1996; 96(4): 237-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8922491

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Systemic granulomatous disease in a horse grazing pasture containing vetch (Vicia sp.). Author(s): Woods LW, Johnson B, Hietala SK, Galey FD, Gillen D. Source: J Vet Diagn Invest. 1992 July; 4(3): 356-60. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1515503

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Systemic granulomatous disease in cattle in California associated with grazing hairy vetch (Vicia villosa). Author(s): Johnson B, Moore J, Woods LW, Galey FD. Source: J Vet Diagn Invest. 1992 July; 4(3): 360-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1515504

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Tetracycline and niacinamide for the treatment of sterile pyogranuloma/granuloma syndrome in a dog. Author(s): Rothstein E, Scott DW, Riis RC.

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Source: Journal of the American Animal Hospital Association. 1997 NovemberDecember; 33(6): 540-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9358425 •

The effect of sho-saiko-to on concentration of vitamin E in serum and on granuloma formation in carrageenin cotton pellet-induced granuloma rats. Author(s): Yoshida K, Mizukawa H, Honmura A, Uchiyama Y, Nakajima S, Haruki E. Source: The American Journal of Chinese Medicine. 1994; 22(2): 183-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7992818

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The effect of sho-saiko-to on the concentration of acid soluble glycoprotein in serum and on granuloma formation in carrageenin cotton pellet-induced granuloma rats. Author(s): Yoshida K, Mizukawa H, Honmura A, Uchiyama Y, Kaku H, Nakajima S, Haruki E. Source: The American Journal of Chinese Medicine. 1993; 21(2): 171-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7694453

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Treatment of recurrent eosinophilic granuloma with systemic therapy. Author(s): Song A, Johnson TE, Dubovy SR, Toledano S. Source: Ophthalmic Plastic and Reconstructive Surgery. 2003 March; 19(2): 140-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644761

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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WebMDHealth: 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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Granulomas

Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to granulomas; 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 Sarcoidosis Source: Integrative Medicine Communications; www.drkoop.com

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Herbs and Supplements Ashwagandha Source: Prima Communications, Inc.www.personalhealthzone.com Cinnamomum Alternative names: Cinnamon; Cinnamomum zeylanicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Withania Ashwagandha Alternative names: Ashwagandha; Withania somnifera L. 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. PATENTS ON GRANULOMAS 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.8 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 “granulomas” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on granulomas, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Granulomas By performing a patent search focusing on granulomas, 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 will tell you how to obtain this information later in the chapter. The following is an 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on granulomas: •

Compositions and methods for treating skin conditions and promoting wound healing Inventor(s): Band; Philip A. (Brooklyn, NY), Rothman; John (Lebanon, NJ) Assignee(s): John Morris Co., Inc. (South Plainfield, NJ) Patent Number: 5,047,249 Date filed: March 3, 1989 Abstract: This invention relates to activated protein-containing compositions comprising reducing agents, oxidizing agents and/or anti-oxidants and methods of use. The therapeutic compositions and methods of the present invention are particularly effective in promoting wound healing, and in inhibiting certain skin disorders, including eczema and seborrhea, sclerodema and acne. The therapeutic compositions and methods of the present invention have also shown enhanced effect as veterinary tools in reducing the debilitation associated with certain skin conditions in mammals including eczematoid dermatitis, chronic dermatitis, equine exuberant granuloma ("proud flesh"), decubitis ulcers, and canine cutaneous granulomas ("lick" granuloma). Excerpt(s): This invention relates to therapeutic compositions using novel activated protein-containing ingredients and includes reducing agents and optionally, oxidizing agents and/or anti-oxidants. The therapeutic compositions of the present invention are particularly effective in promoting wound healing, and in inhibiting certain skin disorders, including eczema and seborrhea, dandruff, psoriases and other rash-like indications, scleroderma and acne. The therapeutic methods of the present invention have also shown enhanced effect as veterinary tools in reducing the debilitation associated with certain skin conditions in mammals including eczematoid dermatitis, chronic dermatitis, equine exuberant granuloma ("proud flesh"), decubitis ulcers, and canine cutaneous granulomas ("lick" granuloma). U.S. Pat. No. 4,438,102 describes compositions which are useful for promoting the growth of normal dermal and epidermal tissue, and described as being useful to promote wound healing in the soft keratin tissue of the epidermis. The compositions of the patent are described as containing defined percentages of thioglycollic acid, ammonium hydroxide, glycerine, citric acid, hydrogen peroxide, gelatin, a lower alkanol, and a solvent such as acetone or diethyl ether. Several examples of wound healing are provided in the specification. The commercial gelatins described in the patent do not contain sufficient cysteinyl residues to covalently bind to keratinous tissue, especially skin and the patent does not disclose that the gelatin covalently binds to skin. U.S. Pat. No. 3,954,974 describes disinfectant emulsions comprised of hydrogen peroxide in an oil-in-water phase. Exemplary compositions comprise hydrogen peroxide, an emulsifier or surfactant, an oil or gel and water. Certain embodiments may additionally include solvents. The compositions of the patent may be used for disinfecting hands and for treating skin diseases, irritations and injuries. Web site: http://www.delphion.com/details?pn=US05047249__

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Dermal formulation for granuloma annulare Inventor(s): Wise; Ronald D. (9037 Kildare, Skokie, IL 60076) Assignee(s): none reported Patent Number: 5,219,571 Date filed: May 13, 1992 Abstract: A dermatological formulation or topical preparation containing fine grain bentonite and a lipophilic agent is provided to treat granuloma annulare dermatosis of the skin. Excerpt(s): Granuloma annulare (G.A.) is a dermatosis of unknown cause characterized by papules that are usually present in an annular configuration. It has been reported to follow insect bites, sun exposure and trauma. Some cases appear to be due to hereditary predisposition since the lesions have occurred in identical twins and siblings as well as in more than one generation of patients. It is usually idiopathic. The most common type of G.A. occurs in children and young adults. Lesions are usually asymptomatic, skincolored, erythematous or violaceous, well defined, dome shaped papules often arranged in a complete or half circle. Solitary lesions may also be present. Lesions are most commonly seen on the dorsa of the hands and feet, but may appear on the forearms, arms, lower legs, and thighs. The face and scalp are rarely affected. Other types of G.A. include a variant with larger, deep, dermal or subcutaneous nodules which may occur on the palms, legs, buttocks or scalp. The perforating type of G.A. manifests itself as small papules with central umbilication. These lesions are most frequently reported to occur on the hands and fingers. A more rarely encountered variant of G.A. presents as circinate erythematous lesions usually on the trunk. In older adults, the disseminated form of G.A. is more commonly seen. Hundreds to thousands of individual papules arise anywhere on the skin but with usual marked involvement of the trunk. Web site: http://www.delphion.com/details?pn=US05219571__

•

Method of screening for arterial chlamydial granuloma Inventor(s): Kuo; Cho-chou (Seattle, WA), Shor; Allan (76 Klip Street, Observatory Extension, Johannesburg 2000, ZA) Assignee(s): Board of Regents of the University of Washington (Seattle, WA), Shor; Allan (Johannesburg, ZA) Patent Number: 5,424,187 Date filed: June 12, 1992 Abstract: Method of diagnosing arterial chlamydial granuloma by detecting in a biological sample both a first marker associated with Chlamydia pneumoniae and a second marker associated with arterial granuloma. Therapeutic composition for treating arterial chlamydial granulomatous disease, including an anti-Chlamydia pneumoniae agent and a granuloma inhibitor. Excerpt(s): This invention relates to diagnosis and treatment of granulomatous disease in Chlamydia pneumoniae-infected arterial tissues. Chlamydia pneumoniae strain TWAR is a recently identified third species of Chlamydia that is unique based on serological, morphological, and DNA sequence homology (2,8; see the appended Citations). Humans are reportedly the sole host of C. pneumoniae. Chlamydia are obligate intracellular bacteria. C. trachomatis and C. pneumoniae are human pathogens,

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while C. psittaci is an animal pathogen (1,18) which may incidentally infect humans. C. pneumoniae causes respiratory infections, while C. trachomatis causes mainly oculogenital infections. The primary syndrome caused by infection of humans with the arian strains of C. psittaci is a pneumonia known as psittacosis or ornithosis. The major clinical manifestations of C. pneumoniae infection are pneumonia, bronchitis, pharyngitis, and sinusitis (3,11). C. pneumoniae infection has been associated with about 10% of community-acquired pneumonia. The infections are geographically widespread. Antibody prevalence studies have shown that virtually everyone is infected with C. pneumoniae at some time and that reinfection is common. Web site: http://www.delphion.com/details?pn=US05424187__ •

Surgical and dental procedures using laser radiation Inventor(s): Levy; Guy (Marseille, FR) Assignee(s): Laser Medical Technology, Inc. (San Clemente, CA) Patent Number: 5,194,005 Date filed: May 15, 1989 Abstract: Laser radiation having a selected wavelength and in the form of pulses having a selected pulse duration, repetition rate and energy content per pulse, is employed for performing a variety of dental and medical procedures, including treatment of cysts and granulomas in the gum, and cutting of dentin, cementum, dental root material, bone and metal. Cavities and openings in teeth and bones can be filled with a mixture containing hydroxyapatite and phosphoric acid, mixed together to form a paste, and the resulting mixture, after being introduced into the openign or cavity, can be cured and hardened by application of pulses of defocussed laser radiation. Excerpt(s): The present invention relates to surgical and dental procedures utilizing laser radiation. In the treatment of various dental and other medical conditions, it is frequently necessary to remove bone, dentin, cementum or dental root material, and it is desirable to do so without subjecting the patient to adverse side effects. Frequently, when performing medical procedures within the oral cavity, the practitioner encounters metal bodies introduced by previous dental procedures, such bodies being constituted by metal filling material, metal pins, and chrome posts used to secure dental prostheses in place, and it is necessary to cut these bodies, again without producing harmful side effects. Web site: http://www.delphion.com/details?pn=US05194005__

Patent Applications on Granulomas As of December 2000, U.S. patent applications are open to public viewing.9 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 granulomas:

9

This has been a common practice outside the United States prior to December 2000.

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Implantable device with free-flowing exit and uses thereof Inventor(s): Schwartz, Anthony H.; (Owings Mills, MD) Correspondence: Hogan & Hartson Llp; One Tabor Center, Suite 1500; 1200 Seventeenth ST; Denver; CO; 80202; US Patent Application Number: 20030208166 Date filed: May 1, 2003 Abstract: The present invention provides means for keeping the lumens and the distal orifices of catheters and like articles free of undesirable granulation tissues, granulomas, and the like. The catheter of the invention overcomes the problem of catheter occlusion by providing an immediately available source of an anti-neoplastic agent that minimizes or prevents formation of granulation tissue or granulomas at the tip and/or in the lumen of the catheter, thereby maintaining catheter patency. The catheter comprises a body with an exterior surface and a distal end, wherein at least the distal end comprises an anti-neoplastic agent to prevent or minimize catheter occlusion when the distal end of the catheter is in contact with a bodily tissue and/or fluid. In one embodiment, the anti-neoplastic agent is applied to the catheter as a coating. In another embodiment, the anti-neoplastic agent is an integral part of the catheter material. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/380,126, filed May 6, 2002. This invention relates to implantable catheters and like devices which are coated or compounded with an anti-neoplastic agent which prevents fibroblast proliferation or formation of granulation tissue or granulomas, thereby maintaining catheter patency. In many patient treatment applications, it is necessary or desirable for the catheter to remain in place for an extended period of time, which may range from several days to several years. For example, in recent years implantable catheters have been developed for use as access ports for insulin therapy, chronic pain management, chemotherapy, nutrition, and peritoneal dialysis. Other applications may include delivery of medicaments such as hypertensive medications, other cardiovascular medications, and medications to treat disorders of the brain and endocrine system. However, the implanted catheter lumen is susceptible to a number of complications such as occlusion. In some forms, catheter occlusions comprise granulation tissue or granulomas. When an occlusion occurs, the catheter must be replaced or the lumen otherwise cleared before infusion of the medical fluids can be resumed. However, occlusion removal in an implanted catheter can be difficult, and removal is not a desirable alternative. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Preventives/remedies for granuloma Inventor(s): Jishage, Kou-ichi; (Shizuoka, JP), Suzuki, Hiroshi; (Shizuoka, JP) Correspondence: Morrison & Foerster Llp; 1650 Tysons Boulevard; Suite 300; Mclean; VA; 22102; US Patent Application Number: 20030171323 Date filed: December 16, 2002 Abstract: A preventive or therapeutic agent for granuloma, specifically for granuloma occurring after ligation of a deferent duct, comprising an antagonist against the scavenger receptor of macrophage, such as antibody, as an active ingredient.

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Excerpt(s): The present invention relates to a preventive and/or therapeutic agent for granuloma, specifically granuloma occurring after ligation of a deferent duct. It is believed that, after ligation of deferent duct, one of the sterilization surgeries, sperm are processed through decomposition and dissolution in the epididymal cavity and phagocytosis by macrophages. Phagocytosis by macrophages is generally known to occur through scavenger receptors expressed on the cell surface of macrophages, and the like. On the other hand, as a side effect after ligation of a deferent duct, sperm granuloma is known to occur in a small percentage of the patients and to be frequently accompanied by pain. Though anti-inflammatory agents have been used for the treatment, little is known on the cause and the mechanism of the onset of the symptoms, and hence there are no known fully effective preventive or therapeutic agents. 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 granulomas, 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 “granulomas” (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 granulomas. You can also use this procedure to view pending patent applications concerning granulomas. 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 5. BOOKS ON GRANULOMAS Overview This chapter provides bibliographic book references relating to granulomas. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on granulomas 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 “granulomas” (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 granulomas: •

Diseases of the Liver and Biliary System, Eleventh Edition Source: Malden, MA: Blackwell Science, Inc. 2002. 706 p. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: Designed to serve practicing physicians, surgeons and pathologists, as well as clinical students, this textbook presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The text offers 38 chapters: anatomy and function; the assessment of liver function; biopsy of the liver; the hematology of liver disease; ultrasound, computed tomography (CT scan) and magnetic resonance imaging (MRI); hepatocellular failure; hepatic encephalopathy; acute liver failure; ascites (fluid accumulation); the portal venous system and portal hypertension; the hepatic artery and

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hepatic vein, and the liver in circulatory failure; jaundice; cholestasis; primary biliary cirrhosis (PBC); sclerosing cholangitis; viral hepatitis, including general features, hepatitis A, hepatitis E, and other viruses; hepatitis B virus and hepatitis Delta virus; hepatitis C virus; chronic hepatitis, its general features and autoimmune chronic disease; drugs and the liver; hepatic cirrhosis (scarring); alcohol and the liver; iron overload states; Wilson's disease; nutritional and metabolic liver diseases; the liver in infancy and childhood; the liver in pregnancy; the liver is systemic disease, granulomas, and hepatic trauma; the liver in infections; nodules and benign liver lesions; malignant liver tumors; the role of interventional radiology and endoscopy in imaging of the biliary tract; cysts and congenital biliary abnormalities; gallstones and inflammatory gallbladder diseases; benign stricture of the bile ducts; diseases of the ampulla of Vater and the pancreas; tumors of the gallbladder and bile ducts; and hepatic transplantation. The text includes full-color and black-and-white illustrations and photographs. A detailed subject index concludes the volume.

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 “granulomas” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “granulomas” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “granulomas” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Pathology of Granulomas and Neoplasms of the Nose and Paranasal Sinuses by Imrich Friedman; ISBN: 0443014108; http://www.amazon.com/exec/obidos/ASIN/0443014108/icongroupinterna

Chapters on Granulomas In order to find chapters that specifically relate to granulomas, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and granulomas 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 “granulomas” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on granulomas: •

Temporal Bone Granulomas and Dystrophies Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 801-811. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X.

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Summary: Granulomatous disease and osteodystrophy are a diverse group of disorders that include osseous dysplasia, histiocytic proliferation, autoimmune disorders, and infectious diseases. This chapter on temporal bone granulomas and dystrophies is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. The authors discuss osteodystrophies and dysplasias, including Paget's disease of bone, fibrous dysplasia, osteogenesis imperfecta, osteopetrosis, endosteal hyperostosis, and osteitis fibrosa cystica; histiocytic proliferation, notably Langerhans cell histiocytosis; and autoimmune disorders, including Wegener's granulomatosis and sarcoidosis. The authors note that most of these processes are not common, but they are important to otolaryngologists. Local behavior can be aggressive, and audiologic, vestibular, or facial nerve dysfunction can result. 5 figures. 1 table. 73 references. •

Benign Granulomatous Processes Source: in Bork, K., et al. Diseases of the Oral Mucosa and the Lips. Orlando, FL: W.B. Saunders Company. 1993. p. 226-236. 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. Summary: This chapter, from a textbook on diseases of the oral mucosa and the lips, discusses benign granulomatous processes. Mucocele is a generic term used to refer to lesions that result from trauma or obstruction of minor salivary gland ducts. Topics include mucous extravasation phenomenon, mucous retention cysts, ranula, superficial mucoceles, pyogenic granuloma, traumatic (eosinophilic) granuloma of the tongue, and other granulomatous diseases, including Melkersson-Rosenthal syndrome, sarcoidosis, Heerfordt's syndrome, sarcoidal foreign body granulomas, and multicentric reticulohistiocytosis. For each topic, the authors describe the histology and clinical features and present brief therapeutic recommendations. Full-color photographs illustrate the chapter; references are provided for some sections. 25 figures. 58 references. (AA-M).

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CHAPTER 6. PERIODICALS AND NEWS ON GRANULOMAS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover granulomas.

News Services and Press Releases One of the simplest ways of tracking press releases on granulomas 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 “granulomas” (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 granulomas. 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 “granulomas” (or synonyms). The following was recently listed in this archive for granulomas: •

Fish Tank Granuloma Frequently Misdiagnosed Source: Reuters Medical News Date: December 01, 1997

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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 “granulomas” (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 “granulomas” (or synonyms). If you know the name of a company that is relevant to granulomas, 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/. 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 “granulomas” (or synonyms).

Academic Periodicals covering Granulomas Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to granulomas. In addition to

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these sources, you can search for articles covering granulomas 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 7. 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 granulomas. 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 nonprofit 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 granulomas. 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

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to granulomas: Cyclophosphamide •

Systemic - U.S. Brands: Cytoxan; Neosar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202174.html

Erythromycins •

Systemic - U.S. Brands: E.E.S.; E-Base; E-Mycin; ERYC; EryPed; Ery-Tab; Erythro; Erythrocin; Erythrocot; Ilosone; Ilotycin; My-E; PCE; Wintrocin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202223.html

Interferon, Gamma •

Systemic - U.S. Brands: Actimmune http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202631.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 granulomas 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 “granulomas” (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 granulomas: •

T-cell depleted stem cell enriched cellular produc (trade name: NONE ASSIGNED) http://www.rarediseases.org/nord/search/nodd_full?code=1132

•

Interferon gamma 1-b (trade name: Actimmune) http://www.rarediseases.org/nord/search/nodd_full?code=118

•

T-cell depleted stem cell enriched cellular produc (trade name: NONE Assigned) http://www.rarediseases.org/nord/search/nodd_full?code=1232

•

Interferon gamma l-b (trade name: Acctimmune) http://www.rarediseases.org/nord/search/nodd_full?code=600

•

Etanercept (trade name: Enbrel) http://www.rarediseases.org/nord/search/nodd_full?code=975

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 Institute10: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

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

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

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

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

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.11 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:12 •

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

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

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

•

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/

•

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

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

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/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

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

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

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

11

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). 12 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

•

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 NLM Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “granulomas” (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 26059 160 168 78 146 26611

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “granulomas” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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 Biologists18 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.19 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.20 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/.

18 Adapted 19

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. 20 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.

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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 granulomas 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 granulomas. 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 granulomas. 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 “granulomas”:

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Benign Tumors http://www.nlm.nih.gov/medlineplus/benigntumors.html Bone Marrow Transplantation http://www.nlm.nih.gov/medlineplus/bonemarrowtransplantation.html Hepatitis C http://www.nlm.nih.gov/medlineplus/hepatitisc.html Immune System and Disorders http://www.nlm.nih.gov/medlineplus/immunesystemanddisorders.html Sarcoidosis http://www.nlm.nih.gov/medlineplus/sarcoidosis.html Skin Diseases http://www.nlm.nih.gov/medlineplus/skindiseases.html 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 granulomas. 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: •

Sarcoidosis Source: Toronto, Ontario: Canadian Liver Foundation. 200x. 1 p. Contact: Available from Canadian Liver Foundation. Suite 1500, 2235 Sheppard Avenue East, Toronto Ontario, M2J 5B5. (416) 491-3353 or (800) 563-5483. Fax (416) 491-4952. Email: [email protected]. Website: [email protected]. PRICE: Full-text available online at no charge; Contact organization for print copies. Summary: This fact sheet, from the Canadian Liver Foundation, reviews sarcoidosis, a multisystem disease of unknown cause in which nests of cells appear in many tissues, including the lung, lymph nodes, and liver. Written in question-and-answer format, the fact sheet covers the symptoms and physical complications of sarcoidosis, and treatment options. Liver biopsy reveals hepatic granulomas in approximately 75 percent of patients. There is no specific treatment for sarcoidosis; individual symptoms are treated as necessary. The fact sheet concludes with the contact information for the Canadian Liver Foundation (www.liver.ca or 800-563-5483).

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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 ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to granulomas. 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. 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

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to granulomas. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with granulomas. 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 granulomas. 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. The Directory of Health Organizations database can be accessed via the Internet at

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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 “granulomas” (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 “granulomas”. 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 “granulomas” (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 “granulomas” (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.21

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

21

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)22: •

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)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

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/

22

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

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

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

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

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

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

•

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

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

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

•

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

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

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

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

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

•

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

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

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/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

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

•

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/

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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/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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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

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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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

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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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 granulomas: •

Basic Guidelines for Granulomas Granuloma inguinale Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000636.htm

•

Signs & Symptoms for Granulomas Edema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm Swelling Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003103.htm

•

Diagnostics and Tests for Granulomas Culture of tissue sample Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm Erosion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003225.htm

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Punch biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003840.htm •

Background Topics for Granulomas Endemic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002362.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Safe sex practices Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001949.htm Subcutaneous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002297.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

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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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GRANULOMAS 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] 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] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [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] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [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] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [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] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adoptive Transfer: Form of passive immunization where previously sensitized

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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 immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [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] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

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] 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] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [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] 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] Allograft: An organ or tissue transplant between two humans. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [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] Alpha-helix: One of the secondary element of protein. [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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and

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atomic weight 26.98. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Alveolitis: Inflammation of an alveolus. Called also odontobothritis. [EU] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] 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 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] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] 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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] 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] 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] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory

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and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] 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]

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] 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] Anticoagulants: Agents that prevent blood clotting. Naturally occurring agents in the blood are included only when they are used as drugs. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [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-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] 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] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [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] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [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] Antitoxin: A purified antiserum from animals (usually horses) immunized by injections of a toxin or toxoid, administered as a passive immunizing agent to neutralize a specific bacterial toxin, e.g., botulinus, tetanus or diphtheria. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU]

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Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [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] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [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] 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] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]

Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Aseptic: Free from infection or septic material; sterile. [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 Endopeptidases: A sub-subclass of endopeptidases that depend on an aspartic acid residue for their activity. EC 3.4.23. [NIH] Aspiration: The act of inhaling. [NIH] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes

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have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [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 variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [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] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autopsy: Postmortem examination of the body. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axillary lymph nodes: Lymph nodes found in the armpit that drain the lymph channels from the breast. [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] Backcross: A cross between a hybrid and either one of its parents. [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 toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [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

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or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] 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]

Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Berylliosis: A lung disease caused by exposure to metallic beryllium or its soluble salts. [NIH]

Beryllium: An element with the atomic symbol Be, atomic number 4, and atomic weight 9.01218. Short exposure to this element can lead to a type of poisoning known as berylliosis. [NIH]

Beta Rays: A stream of positive or negative electrons ejected with high energy from a disintegrating atomic nucleus; most biomedically used isotopes emit negative particles (electrons or negatrons, rather than positrons). Cathode rays are low-energy negative electrons produced in cathode ray tubes, also called television tubes or oscilloscopes. [NIH] Bewilderment: Impairment or loss of will power. [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] Biliary Atresia: Atresia of the biliary tract, most commonly of the extrahepatic bile ducts. [NIH]

Biliary Tract: The gallbladder and its ducts. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU]

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Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [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 cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [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] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] 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] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH] Bladder: The organ that stores urine. [NIH] Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [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 vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [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

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with marrow cells. [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] 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] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy on the interstitial lung tissue. [NIH] Bronchoscope: A thin, lighted tube used to examine the inside of the trachea and bronchi, the air passages that lead into the lungs. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buccal mucosa: The inner lining of the cheeks and lips. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [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] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [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]

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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] 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] 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] 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 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] 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] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] 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] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Celiac Artery: The arterial trunk that arises from the abdominal aorta and after a short course divides into the left gastric, common hepatic and splenic arteries. [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 Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [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 Degranulation: The process of losing secretory granules (secretory vesicles). This

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occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by exocytosis. [NIH] Cell Division: The fission of a cell. [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 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] 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] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [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] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Cherubism: A fibro-osseous hereditary disease of the jaws. The swollen jaws and raised eyes give a cherubic appearance; multiple radiolucencies are evident upon radiographic

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examination. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholecystectomy: Surgical removal of the gallbladder. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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] Chondrocytes: Polymorphic cells that form cartilage. [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 lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [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 phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [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] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Clavicle: A long bone of the shoulder girdle. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

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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] 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] Coccidioidomycosis: An infectious disease caused by a fungus, Coccidioides immitis, that is prevalent in the western United States and is acquired by inhalation of dust containing the spores. [NIH] Codons: Any triplet of nucleotides (coding unit) in DNA or RNA (if RNA is the carrier of primary genetic information as in some viruses) that codes for particular amino acid or signals the beginning or end of the message. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] 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] 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] 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,

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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] 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] 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 axial 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 CAT scan, computed tomography (CT scan), or computerized tomography. [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] 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] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [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] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective

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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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constriction: The act of constricting. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [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] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [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] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cor pulmonale: Heart disease that results from resistance to the passage of blood through the lungs; it often leads to right heart failure. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [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 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 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] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH]

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Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Croton Oil: Viscous, nauseating oil obtained from the shrub Croton tiglium (Euphorbaceae). It is a vesicant and skin irritant used as pharmacologic standard for skin inflammation and allergy and causes skin cancer. It was formerly used as an emetic and cathartic with frequent mortality. [NIH] Cryostat: A batchwise operating apparatus in which a cryogenic liquid or solid is used to maintain by evaporation a cryotemperature which needs not be constant but may vary in a predetermined fashion. [NIH] Cryptococcosis: Infection with a fungus of the species Cryptococcus neoformans. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]

Curette: A spoon-shaped instrument with a sharp edge. [NIH] Cutaneous: Having to do with the skin. [NIH] 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] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cysteine Endopeptidases: Endopeptidases which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22. [NIH] Cysteinyl: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cysticercus: The larval form of various tapeworms of the genus Taenia. [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] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH]

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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] 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] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [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] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] 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] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dexmedetomidine: A selective inhibitor of receptors, adrenergic alpha-2 that has analgesic and sedative properties. Medetomidine is the other racemic form. [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] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or

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concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [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] Dipeptidases: Exopeptidases that specifically act on dipeptides. EC 3.4.13. [NIH] Dipeptides: Peptides composed of two amino acid units. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [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] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [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] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [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

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effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [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] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] 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] 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] 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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] 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] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [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] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be

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done as treatment to block the flow of blood to a tumor. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emetic: An agent that causes vomiting. [EU] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [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] 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] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [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 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] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [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-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] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

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Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [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] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophilic Gastroenteritis: Infection and swelling of the lining of the stomach, small intestine, or large intestine. The infection is caused by white blood cells (eosinophils). [NIH] Eosinophilic Granuloma: The most benign clinical form of Langerhans-cell histiocytosis, which involves localized nodular lesions of the gastric mucosa, small intestine, bones, lungs, or skin, with infiltration by eosinophils. The proliferating cell that appears to be responsible for the clinical manifestations is the Langerhans cell. [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] 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] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [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] Epistaxis: Bleeding from the nose. [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]

Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH]

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Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excisional biopsy: A surgical procedure in which an entire lump or suspicious area is removed for diagnosis. The tissue is then examined under a microscope. [NIH] Excrete: To get rid of waste from the body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expander: Any of several colloidal substances of high molecular weight. used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood. called also extender. [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

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laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [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] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [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] Fold: A plication or doubling of various parts of the body. [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

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of free radical damage is being actively investigated. [NIH] Frozen Sections: Thinly cut sections of frozen tissue specimens prepared with a cryostat or freezing microtome. [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] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallium: A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [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] Gastritis: Inflammation of the stomach. [EU] 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] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] 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

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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 Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Products, rev: Trans-acting nuclear proteins whose functional expression are required for HIV viral replication. Specifically, the rev gene products are required for processing and translation of the HIV gag and env mRNAs, and thus rev regulates the expression of the viral structural proteins. rev can also regulate viral regulatory proteins. A cis-acting antirepression sequence (CAR) in env, also known as the rev-responsive element (RRE), is responsive to the rev gene product. rev is short for regulator of virion. [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] Genes, env: DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein (= gene products, rev), termed the rev-responsive element (RRE). [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 testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [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 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] Gingival Hyperplasia: A pathological increase in the depth of the gingival crevice surrounding a tooth at the gum margin. [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]

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]

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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] 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]

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] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] 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] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [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] Granulation Tissue: A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH]

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Granuloma Annulare: Benign granulomatous disease of unknown etiology characterized by a ring of localized or disseminated papules or nodules on the skin and palisading histiocytes surrounding necrobiotic tissue resulting from altered collagen structures. [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] 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]

Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [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] 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] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [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] 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

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and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [NIH] Hepatic: Refers to the liver. [NIH] Hepatic Artery: A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [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] Herpesviridae: A family of enveloped, linear, double-stranded DNA viruses infecting a wide variety of animals. There are three subfamilies based on biological characteristics: Alphaherpesvirinae, Betaherpesvirinae, and Gammaherpesvirinae. [NIH] Heterodimer: Zippered pair of nonidentical proteins. [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]

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] Histology: The study of tissues and cells under a microscope. [NIH] Histoplasma: A mitosporic Onygenales fungal species causing histoplasmosis in humans and animals. Histoplasma capsulatum and its teleomorph Ajellomyces capsulatus are the offending species. [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] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic

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cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [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] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydromorphone: An opioid analgesic made from morphine and used mainly as an analgesic. It has a shorter duration of action than morphine. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] 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] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperostosis: Increase in the mass of bone per unit volume. [NIH] Hyperreflexia: Exaggeration of reflexes. [EU] 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] 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] Hypnotic: A drug that acts to induce sleep. [EU] Hypogammaglobulinemia: The most common primary immunodeficiency in which antibody production is deficient. [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] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or

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discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Idiopathic: Describes a disease of unknown cause. [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] 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] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [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]

Immunodominant Epitopes: Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody. [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] 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] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH]

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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] 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] Incisor: Anything adapted for cutting; any one of the four front teeth in each jaw. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [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] 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]

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]

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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]

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] 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] 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] Instillation: . [EU] 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] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intercellular Adhesion Molecule-1: A cell-surface ligand with a role in leukocyte adhesion and inflammation. Its production is induced by gamma-interferon and it is required for neutrophil migration into inflamed tissue. [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]

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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-5: Factor promoting eosinophil differentiation and activation in hematopoiesis. It also triggers activated B-cells for a terminal differentiation into Ig-secreting cells. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] 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, implant radiation, or interstitial radiation therapy. [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] Intracellular: Inside a cell. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intravesical: Within the bladder. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] 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]

Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [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] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented

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epithelium. [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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] ITP: A blood disorder characterized by low platelet levels. [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]

Jaw Cysts: Saccular lesions lined with epithelium and contained within pathologically formed cavities in the jaw; also nonepithelial cysts (pseudocysts) as they apply to the jaw, e.g., traumatic or solitary cyst, static bone cavity, and aneurysmal bone cyst. True jaw cysts are classified as odontogenic or nonodontogenic. [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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Keyhole: A carrier molecule. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]

Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lacrimal: Pertaining to the tears. [EU] Lacrimal gland: The small almond-shaped structure that produces tears; located just above the outer corner of the eye. [NIH] Lactation: The period of the secretion of milk. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large

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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] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [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] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] 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]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Cycle Stages: The continuous sequence of changes undergone by metamorphosing insects and other animals during the post-embryonic development process. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Linolenic Acids: Eighteen-carbon essential fatty acids that contain three double bonds. [NIH] Lipid: Fat. [NIH]

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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] Lipopolysaccharides: 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] 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] Liquor: 1. A liquid, especially an aqueous solution containing a medicinal substance. 2. A general term used in anatomical nomenclature for certain fluids of the body. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [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] 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] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries

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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] 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] Lymphedema: Edema due to obstruction of lymph vessels or disorders of the lymph nodes. [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] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphocytosis: Excess of normal lymphocytes in the blood or in any effusion. [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] Lymphokine-activated killer cells: White blood cells that are stimulated in a laboratory to kill tumor cells. Also called LAK cells. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphomatoid Granulomatosis: An angiocentric and angiodestructive lymphoreticular proliferative disorder primarily involving the lungs. Histologically it simulates malignant lymphoma and in some cases may progress to lymphoma. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [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 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] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [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

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radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [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] 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]

Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH] Mannans: Polysaccharides consisting of mannose units. [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] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [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] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [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

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active transport, several enzymatic activities and membrane formation. [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] 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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Processes: Conceptual functions or thinking in all its forms. [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] Metalloendopeptidases: Endopeptidases which use a metal, normally zinc, in the catalytic mechanism. This group of enzymes is inactivated by metal chelators. EC 3.4.24. [NIH] 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] 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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [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] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [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]

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Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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 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] Monocyte Chemoattractant Protein-1: A chemokine that is a chemoattractant for human monocytes and may also cause cellular activation of specific functions related to host defense. It is produced by leukocytes of both monocyte and lymphocyte lineage and by fibroblasts during tissue injury. [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] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH]

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Mycobacteriosis: Any disease caused by Mycobacterium other than M. tuberculosis, M. bovis, and M. avium. [NIH] Mycosis: Any disease caused by a fungus. [EU] Mycotic: Pertaining to a mycosis; caused by fungi. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myristate: Pharmacological activator of protein kinase C. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] 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 pain, food poisoning, and various enteroviruses. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] 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] 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] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [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] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [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] 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] Neutralization: An act or process of neutralizing. [EU]

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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] Niacinamide: An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. [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]

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] 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] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [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] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle

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it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [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] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [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] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Ornithosis: Infection with Chlamydophila psittaci (formerly Chlamydia psittaci), transmitted to man by inhalation of dust-borne contaminated nasal secretions or excreta of infected birds. This infection results in a febrile illness characterized by pneumonitis and systemic manifestations. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteitis Fibrosa Cystica: A fibrous degeneration, cyst formation, and the presence of fibrous nodules in bone, usually due to hyperparathyroidism. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH]

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Osteodystrophy: Defective bone formation. [EU] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteogenesis Imperfecta: A collagen disorder resulting from defective biosynthesis of type I collagen and characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. There are four major types, I-IV. [NIH] Osteopetrosis: Excessive formation of dense trabecular bone leading to pathological fractures, osteitis, splenomegaly with infarct, anemia, and extramedullary hemopoiesis. [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] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Otology: The branch of medicine which deals with the diagnosis and treatment of the disorders and diseases of the ear. [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] 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] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or

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concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] 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 Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [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] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Paratuberculosis: An infectious disease caused by Mycobacterium paratuberculosis. Characteristics include chronic debilitation and weight loss. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Particle Accelerators: Devices which accelerate electrically charged atomic or subatomic particles, such as electrons, protons or ions, to high velocities so they have high kinetic energy. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [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

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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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvis: The lower part of the abdomen, located between the hip bones. [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] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [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] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Periapical Granuloma: Chronic nonsuppurative inflammation of periapical tissue resulting from irritation following pulp disease or endodontic treatment. [NIH] Periapical Tissue: Tissue surrounding the apex of a tooth, including the apical portion of the periodontal membrane and alveolar bone. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [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 Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [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 the inside of the abdominal wall and the visceral peritoneum covering the bowel, the

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mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] 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] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharyngitis: Inflammation of the throat. [NIH] 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] Phorbol: Class of chemicals that promotes the development of tumors. [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] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [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] 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] 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] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH]

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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] 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] 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] 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] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [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] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleated: Particular three-dimensional pattern of amyloidoses. [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 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] 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] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarthritis: An inflammation of several joints together. [EU] 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]

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]

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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 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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [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] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoperative: Preceding an operation. [EU] 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] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Progeny: The offspring produced in any generation. [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]

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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] Progressive disease: Cancer that is increasing in scope or severity. [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] Prophylaxis: An attempt to prevent disease. [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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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 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] 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] Proxy: A person authorized to decide or act for another person, for example, a person having durable power of attorney. [NIH] Pruritic: Pertaining to or characterized by pruritus. [EU] Pseudocysts: A collection of enzyme-rich pancreatic fluid and tissue debris arising within areas of necrosis or an obstructed smaller duct. [NIH] Psittaci: Causal agent of ornithosis. [NIH] Psittacosis: A lung disease caused by a Chlamydia bacterium; occurs in domestic fowls, ducks, pigeons, turkeys and many wild birds and is contracted by man by contact with these birds; the human symptoms are headache, nausea, epistaxis and fever and usually with added symptoms. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU]

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Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] 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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [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 Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Sarcoidosis: A disease of unknown etiology characterized by tuberclelike, granulomatous nodules which may affect the skin, the lungs, the lymph nodes, the bones of the distal extremities, the conjunctiva, the lacrimal gland, the retina and the uveal tract. [NIH] Pulmonary Veins: The veins that return the oxygenated blood from the lungs to the left atrium of the heart. [NIH] Pulmonary Veno-Occlusive Disease: Obstruction of the small- and medium-sized pulmonary veins by fibrous proliferation of the intima and media or by thrombosis or a combination of both. [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] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Quiescent: Marked by a state of inactivity or repose. [EU] 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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [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 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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Radicular: Having the character of or relating to a radicle or root. [NIH] Radicular Cyst: Slow-growing fluid-filled epithelial sac at the apex of a tooth with a nonvital pulp or defective root canal filling. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [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] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [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] Ranula: A form of retention cyst of the floor of the mouth, usually due to obstruction of the ducts of the submaxillary or sublingual glands, presenting a slowly enlarging painless deep burrowing mucocele of one side of the mouth. It is also called sublingual cyst and sublingual ptyalocele. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] 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, Adrenergic: Cell-surface proteins that bind epinephrine and/or norepinephrine with high affinity and trigger intracellular changes. The two major classes of adrenergic receptors, alpha and beta, were originally discriminated based on their cellular actions but now are distinguished by their relative affinity for characteristic synthetic ligands. Adrenergic receptors may also be classified according to the subtypes of G-proteins with which they bind; this scheme does not respect the alpha-beta distinction. [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] 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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH]

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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] 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] Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [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] Reinfection: A second infection by the same pathogenic agent, or a second infection of an organ such as the kidney by a different pathogenic agent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [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] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Research Support: Financial support of research activities. [NIH] 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] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [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 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] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous

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membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [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] 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] Rheumatoid Nodule: Subcutaneous nodules seen in 20-30% of rheumatoid arthritis patients. They may arise anywhere on the body, but are most frequently found over the bony prominences. The nodules are characterized histologically by dense areas of fibrinoid necrosis with basophilic streaks and granules, surrounded by a palisade of cells, mainly fibroblasts and histiocytes. [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] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]

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] Rod: A reception for vision, located in the retina. [NIH] 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]

Saline: A solution of salt and water. [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] 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] Sarcoid: A cutaneus lesion occurring as a manifestation of sarcoidosis. [NIH]

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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] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Schistosome: Dermatitis caused by the snail parasite, Schistosoma cercariae. [NIH] Schistosomiasis mansoni: Schistosomiasis caused by Schistosoma mansoni. It is endemic in Africa, the Middle East, South America, and the Caribbean and affects mainly the bowel, spleen, and liver. [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] Sclerae: A circular furrow between the sclerocorneal junction and the iris. [NIH] 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] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Seborrhea: Hypersecretion of sebum with excessive oily secretion from the sweat glands. [NIH]

Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] 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] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] 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] 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] Seminal vesicles: Glands that help produce semen. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence

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(protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [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] Serine Endopeptidases: Any member of the group of endopeptidases containing at the active site a serine residue involved in catalysis. EC 3.4.21. [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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [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] 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]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by 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] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [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]

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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] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solium: Tapeworm of the genus Taenia. The adult form is found in the small intestine of humans and some apes and the metacestode (Cysticercus cellulosae) in the skeletal and cardiac muscle of pigs and in the brain of humans. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [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] 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 Stenosis: Narrowing of the spinal canal. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirochete: Lyme disease. [NIH] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH]

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Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, 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] Splenomegaly: Enlargement of the spleen. [NIH] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Sporotrichosis: The commonest and least serious of the deep mycoses, characterized by nodular lesions of the cutaneous and subcutaneous tissues. It is caused by inhalation of contaminated dust or by infection of a wound. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Standardize: To compare with or conform to a standard; to establish standards. [EU] Steady state: Dynamic equilibrium. [EU] Stellate: Star shaped. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Sterile: Unable to produce children. [NIH] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] 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] 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

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coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [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] 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] 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] Sublingual: Located beneath the tongue. [EU] Submandibular: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [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]

Substrate: A substance upon which an enzyme acts. [EU] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supraclavicular: The depression above the clavicle and lateral to the sternomastoid muscle. [NIH]

Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium

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chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Syncytium: A living nucleated tissue without apparent cellular structure; a tissue composed of a mass of nucleated protoplasm without cell boundaries. [NIH] Synovial: Of pertaining to, or secreting synovia. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] 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] Talampicillin: An ester of ampicillin which is readily hydrolysed on absorption to release ampicillin. It is well absorbed from the gastrointestinal tract resulting in a greater bioavailability of ampicillin than can be achieved with equivalent doses of ampicillin. [NIH] Tamponade: The inserting of a tampon; a dressing is inserted firmly into a wound or body cavity, as the nose, uterus or vagina, principally for stopping hemorrhage. [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] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] 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,

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palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [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] 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] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Expanders: Inflatable reservoirs, usually made of silicone, which are implanted subcutaneously in order to generate tissue needed for surgical reconstruction. After implantation, the reservoir is inflated over several weeks by percutaneous injection of fluid. Once the tissue has grown, the expander is surgically removed and the expanded skin is used to cover the area being reconstructed. [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]

Tocainide: An antiarrhythmic agent which exerts a potential- and frequency-dependent block of sodium channels. [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] 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] Topical: On the surface of the body. [NIH] 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]

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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] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [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] 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] 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] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [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] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tubercular: Of, pertaining to, or resembling tubercles or nodules. [EU] Tuberculomas: Tuberculosis of the skin seen in pathologists and morgue attendants. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tularemia: A plague-like disease of rodents, transmissible to man. It is caused by Francisella tularensis and is characterized by fever, chills, headache, backache, and weakness. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body.

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Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [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]

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] Umbilication: Being or becoming umbilicated; any depression resembling the umbilicus in form. [NIH] Umbilicus: The pit in the center of the abdominal wall marking the point where the umbilical cord entered in the fetus. [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [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] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urogenital System: All the organs involved in reproduction and the formation and release of urine. It includes the kidneys, ureters, bladder, urethra, and the organs of reproduction ovaries, uterus, fallopian tubes, vagina, and clitoris in women and the testes, seminal vesicles, prostate, seminal ducts, and penis in men. [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] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the

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ciliary body and iris in the front of the eye. [NIH] Uveal tract: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vacuole: A fluid-filled cavity within the cytoplasm of a cell. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] 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] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] 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] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] 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 Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [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] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate

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phages establishing the lysogenic response. [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] Visceral Larva Migrans: Infestation of the dermis by various larvae, characterized by bizarre red irregular lines which are broad at one end and fade at the other, produced by burrowing larvae. [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] Vocal cord: The vocal folds of the larynx. [NIH] 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]

Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xenograft: The cells of one species transplanted to another species. [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] Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [NIH]

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INDEX A Abdomen, 71, 139, 147, 159, 171, 174, 181, 184, 196, 199 Abdominal, 64, 79, 139, 148, 155, 162, 171, 183, 184, 201 Abdominal Pain, 139, 162, 201 Aberrant, 28, 139 Ablation, 78, 139 Abortion, 139, 181 Acatalasia, 139, 148 Acceptor, 139, 174, 182, 200 Acetone, 102, 139, 172 Acetylcholine, 139, 179, 180 Acne, 102, 139 Acute renal, 139, 165 Acyl, 89, 139 Adaptability, 139, 148, 149 Adenocarcinoma, 139, 166 Adenoma, 70, 139 Adenosine, 139, 141, 185 Adjuvant, 10, 19, 97, 139, 162 Adoptive Transfer, 32, 139 Adrenal Cortex, 140, 180, 187 Adrenergic, 9, 140, 159, 190 Adverse Effect, 140, 194 Aerosol, 26, 42, 140 Afferent, 140, 161 Affinity, 140, 144, 174, 175, 190, 195 Agonist, 9, 140 Air Sacs, 140, 141 Algorithms, 140, 146 Alimentary, 140 Alkaloid, 140, 178 Allograft, 39, 140 Allopurinol, 58, 59, 70, 140 Alpha Particles, 140, 189 Alpha-helix, 140, 172 Alternative medicine, 112, 140 Aluminum, 50, 86, 140 Alveoli, 52, 141 Alveolitis, 63, 72, 141 Ameliorating, 10, 141 Amino Acid Sequence, 141, 142, 163 Amiodarone, 44, 47, 83, 141 Ampicillin, 36, 141, 198 Ampulla, 108, 141, 150, 158 Anaesthesia, 141, 169 Analgesic, 141, 155, 167, 178, 181

Anatomical, 141, 144, 158, 169, 174, 183, 193 Anemia, 49, 141, 182 Anergy, 18, 141 Aneurysm, 46, 141 Angiitis, 61, 141 Angiogenesis, 97, 141, 176 Animal model, 7, 8, 10, 13, 15, 25, 26, 31, 34, 141 Anions, 141, 171, 197 Annealing, 141, 187 Anorexia, 141, 162 Antianginal, 141, 142 Antiarrhythmic, 141, 142, 199 Antibacterial, 142, 195 Antibiotic, 25, 31, 141, 142, 195 Antibodies, 12, 18, 36, 52, 142, 144, 165, 167, 168, 175, 178, 186, 190 Anticoagulants, 142, 150 Anticonvulsant, 23, 142 Antigen-presenting cell, 142, 155 Anti-infective, 142, 167 Anti-inflammatory, 18, 25, 106, 142, 183 Anti-Inflammatory Agents, 106, 142 Antimicrobial, 142, 155 Antioxidant, 30, 142, 182 Antiseptic, 139, 142 Antiserum, 142 Antitoxin, 21, 142 Antiviral, 142, 162, 170 Anus, 143, 151 Aorta, 88, 143, 148, 202 Apoptosis, 28, 42, 45, 143, 154 Aqueous, 94, 143, 155, 158, 167, 173, 174 Arachidonate 12-Lipoxygenase, 143, 174 Arachidonate 15-Lipoxygenase, 143, 174 Arachidonate Lipoxygenases, 143, 174 Arginine, 28, 143, 180 Arterial, 103, 143, 148, 153, 167, 188, 198 Arteries, 143, 146, 148, 153, 174, 177, 189 Arteriosus, 143, 189 Arteritis, 64, 71, 143 Artery, 141, 143, 153, 157, 183, 189, 193 Ascites, 107, 143, 180 Aseptic, 9, 143, 181 Aspartic, 143, 158 Aspartic Endopeptidases, 143, 158 Aspiration, 6, 45, 58, 95, 143

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Astringents, 143, 177 Astrocytes, 143, 166 Asymptomatic, 6, 21, 25, 103, 139, 144 Atrial, 141, 144, 153, 200 Atrioventricular, 144, 153 Atrium, 144, 153, 189, 200, 202 Atrophy, 39, 88, 144, 160 Attenuated, 144, 202 Attenuation, 10, 63, 144 Atypical, 52, 144 Autoantibodies, 28, 144 Autoantigens, 144 Autoimmune disease, 25, 144 Autoimmunity, 28, 144 Autopsy, 61, 144 Autosuggestion, 144, 167 Axillary, 48, 144 Axillary lymph nodes, 48, 144 B Bacillus, 21, 53, 63, 79, 144 Backcross, 15, 144 Bacterial Infections, 4, 144, 151, 191 Bacterial toxin, 142, 144 Bacteriophage, 144, 200, 202 Bacterium, 8, 35, 40, 42, 144, 165, 188 Barbiturate, 145, 198 Basement Membrane, 145, 160 Basophils, 145, 149, 164, 173 Benign, 4, 6, 108, 109, 128, 139, 145, 159, 165, 179, 190 Benign tumor, 4, 145 Berylliosis, 145 Beryllium, 14, 20, 24, 29, 145 Beta Rays, 145, 157 Bewilderment, 145, 152 Bilateral, 3, 46, 60, 145, 160 Bile, 108, 145, 150, 162, 172, 174, 187, 196 Bile Acids, 145, 162, 196 Bile Acids and Salts, 145 Bile duct, 108, 145, 150, 187 Bile Pigments, 145, 172 Biliary, 57, 90, 107, 145, 150 Biliary Atresia, 57, 90, 145 Biliary Tract, 108, 145 Bioavailability, 145, 198 Biochemical, 13, 94, 145, 146, 147, 164, 199 Biochemical reactions, 146, 199 Biological therapy, 146, 165 Biomarkers, 15, 146 Biopsy, 4, 13, 20, 26, 95, 107, 128, 138, 146, 160, 184 Biopsy specimen, 26, 146

Biosynthesis, 31, 146, 182, 194 Biotechnology, 35, 43, 112, 123, 146 Bioterrorism, 8, 146 Bladder, 146, 171, 188, 201 Blast phase, 146, 150 Blood Platelets, 146, 199 Blood pressure, 146, 148, 167, 178, 187, 189, 195 Blot, 16, 146, 168 Blotting, Western, 146, 168 Body Fluids, 146, 157, 195, 200 Bone Marrow, 44, 63, 70, 73, 83, 128, 146, 150, 168, 175, 195 Bowel, 4, 147, 170, 171, 184, 193, 196, 201 Brachytherapy, 147, 171, 172, 189, 203 Bradykinin, 147, 180 Breeding, 15, 147 Bronchi, 147, 159, 200 Bronchial, 7, 18, 147 Bronchioles, 141, 147 Bronchitis, 104, 147 Bronchoalveolar Lavage, 20, 26, 52, 147 Bronchoalveolar Lavage Fluid, 52, 147 Bronchoscope, 7, 147 Buccal, 5, 147, 174 Buccal mucosa, 5, 147 C Calcitonin, 48, 88, 90, 147 Calcium, 147, 150, 151, 176 Capsular, 12, 147 Capsules, 147, 163 Carbohydrate, 40, 147, 164, 187, 194 Carcinogenic, 148, 170, 181, 188, 196 Carcinogens, 148, 182 Carcinoma, 48, 148 Cardiac, 45, 142, 148, 153, 159, 179, 195, 196 Cardiovascular, 20, 89, 105, 148 Cardiovascular disease, 20, 148 Carotene, 148, 191 Case report, 3, 4, 5, 45, 49, 51, 63, 71, 74, 80, 81, 83, 85, 94, 95, 96, 148, 151 Case series, 148, 151 Catalase, 12, 139, 148 Catheter, 9, 80, 81, 105, 148 Cathode, 145, 148, 157 Causal, 33, 148, 165, 188, 198 Cause of Death, 16, 148 Cecum, 148, 172 Celiac Artery, 148, 166 Cell, 3, 4, 8, 9, 10, 12, 13, 14, 16, 18, 19, 20, 21, 22, 23, 24, 25, 27, 28, 29, 30, 32, 33,

207

34, 35, 36, 37, 39, 40, 41, 42, 46, 47, 48, 49, 50, 51, 55, 56, 57, 60, 61, 64, 67, 69, 70, 71, 73, 74, 75, 77, 80, 88, 90, 97, 98, 106, 109, 117, 140, 142, 143, 144, 146, 148, 149, 150, 151, 152, 154, 155, 157, 158, 159, 160, 162, 163, 165, 166, 167, 168, 170, 171, 172, 173, 176, 177, 178, 179, 181, 182, 183, 185, 186, 190, 191, 193, 195, 197, 198, 199, 200, 201, 202, 203 Cell Adhesion, 25, 148, 170 Cell Count, 25, 148 Cell Death, 28, 29, 143, 148, 163, 179 Cell Degranulation, 10, 148 Cell Division, 144, 149, 154, 165, 177, 186 Cell membrane, 149, 185, 195 Cell proliferation, 20, 30, 149 Cell Survival, 149, 165 Cellulose, 149, 162, 186 Central Nervous System, 23, 25, 74, 139, 149, 157, 165, 178, 181 Cerebral, 49, 81, 82, 149, 153, 159, 160 Cerebrospinal, 9, 49, 149, 194 Cerebrospinal fluid, 9, 49, 149, 194 Cerebrovascular, 148, 149 Cerebrum, 149 Cervical, 82, 97, 149 Cervix, 139, 149 Character, 55, 149, 155, 190 Chemokines, 10, 16, 18, 23, 27, 35, 38, 149 Chemotactic Factors, 90, 149, 152 Chemotaxis, 10, 149 Chemotherapy, 90, 98, 105, 149 Cherubism, 3, 149 Chlorophyll, 150, 162 Cholangitis, 108, 150 Cholecystectomy, 60, 150 Cholestasis, 108, 150 Cholesterol, 44, 46, 49, 52, 53, 72, 76, 77, 78, 81, 88, 89, 145, 150, 153, 167, 174, 176, 196 Chondrocytes, 150, 161 Choroid, 150, 153, 191, 201, 202 Chromaffin System, 150, 158 Chromatin, 143, 150 Chromosomal, 15, 150, 186, 193 Chromosome, 150, 165, 193, 201 Chronic Disease, 8, 108, 150, 173 Chronic lymphocytic leukemia, 75, 150 Chronic myelogenous leukemia, 146, 150 Chronic phase, 13, 150 Circulatory system, 150, 158 Cirrhosis, 108, 150, 187

CIS, 150, 163, 191 Citric Acid, 102, 150 Clavicle, 150, 197 Clinical Medicine, 66, 150, 187 Clinical study, 76, 151 Clinical trial, 6, 123, 151, 190 Cloning, 15, 37, 146, 151 Coccidioidomycosis, 53, 151 Codons, 151, 163, 181 Coenzyme, 151, 180 Colitis, 27, 151 Collagen, 45, 141, 145, 151, 160, 161, 162, 165, 176, 182, 186, 188 Colloidal, 90, 151, 160 Colon, 52, 63, 74, 151, 170, 173, 194, 201 Combination chemotherapy, 98, 151 Common Variable Immunodeficiency, 50, 51, 151 Complement, 27, 151, 152, 163, 170, 176, 178 Complementary and alternative medicine, 93, 100, 152 Complementary medicine, 93, 152 Computational Biology, 123, 152 Computed tomography, 107, 152 Computerized axial tomography, 152 Computerized tomography, 152 Conception, 139, 152, 153 Concomitant, 11, 71, 152 Cones, 152, 191 Confusion, 63, 152, 156, 201 Congestion, 152, 159 Conjugated, 62, 145, 152, 154 Conjunctiva, 44, 45, 152, 189 Connective Tissue, 146, 151, 152, 153, 155, 161, 162, 164, 175, 177, 184, 192, 193, 198 Consciousness, 141, 153, 156, 166 Constriction, 153, 172, 193 Contraceptive, 70, 153 Contraindications, ii, 153 Conus, 153, 189 Convulsions, 142, 145, 153 Cor, 12, 153 Cor pulmonale, 12, 153 Cornea, 97, 153, 193, 197, 202 Corneum, 153, 159 Coronary, 148, 153, 177 Coronary heart disease, 148, 153 Coronary Thrombosis, 153, 177 Corpus, 75, 153, 184, 187, 203 Corpus Luteum, 153, 187 Corpuscle, 154, 160

208

Granulomas

Cortical, 154, 193 Cranial, 154, 161, 165, 181, 184 Croton Oil, 37, 154 Cryostat, 154, 162 Cryptococcosis, 60, 154 Curative, 154, 199 Curettage, 5, 154 Curette, 154 Cutaneous, 46, 50, 51, 54, 60, 66, 71, 73, 81, 83, 85, 94, 95, 98, 102, 154, 173, 174, 196 Cyclic, 27, 154, 165, 180 Cyst, 154, 172, 181, 190 Cysteine, 149, 154, 158 Cysteine Endopeptidases, 154, 158 Cysteinyl, 102, 154 Cysticercus, 53, 55, 81, 82, 154, 195 Cytochrome, 154, 191 Cytochrome b, 154, 191 Cytogenetics, 154, 193 Cytokine, 8, 11, 16, 18, 19, 23, 25, 27, 29, 30, 32, 33, 34, 35, 40, 42, 43, 51, 77, 82, 154, 198 Cytomegalovirus, 47, 155 Cytoplasm, 143, 145, 149, 155, 159, 202 Cytoskeleton, 155, 170 Cytotoxic, 8, 51, 155, 190 D Degenerative, 153, 155, 166 Deletion, 27, 143, 155 Denaturation, 155, 187 Dendrites, 155, 179 Dendritic, 18, 67, 155, 176 Dendritic cell, 18, 67, 155 Density, 155, 174, 186 Dermal, 37, 39, 83, 102, 103, 155 Dermatitis, 84, 102, 155, 157, 193 Dermatosis, 103, 155 Dermis, 155, 198, 203 Detergents, 12, 155 Deuterium, 155, 167 Dexmedetomidine, 10, 155 Diabetes Mellitus, 39, 155, 164, 165 Diagnostic procedure, 101, 112, 155 Diaphragm, 155, 186 Diarrhoea, 155, 162 Diastolic, 155, 167 Diffusion, 155, 169 Digestion, 140, 145, 147, 156, 171, 174, 196 Digestive tract, 156, 194, 196 Dipeptidases, 94, 156 Dipeptides, 156 Diphtheria, 142, 156

Diploid, 156, 186 Direct, iii, 10, 54, 115, 150, 156, 183, 191, 198 Discoid, 25, 156 Discrete, 14, 156 Disinfectant, 102, 156 Disorientation, 152, 156 Dissection, 14, 15, 156 Dissociation, 40, 140, 156 Dissociative Disorders, 156 Distal, 105, 156, 162, 184, 189 Domesticated, 156, 165 Drug Interactions, 116, 156 Drug Resistance, 9, 156 Drug Tolerance, 156, 199 Duct, 105, 106, 141, 157, 160, 188, 192, 196, 198 Duodenum, 145, 157, 158, 166, 183, 196 Dura mater, 157, 177, 182 Dyes, 145, 157 Dysplasia, 109, 157 Dyspnea, 157, 189 E Eczema, 102, 157 Edema, 5, 80, 137, 157, 175, 180 Effector, 10, 12, 32, 139, 151, 157, 172 Effector cell, 12, 157, 172 Efferent, 157, 161 Efficacy, 16, 31, 157 Effusion, 157, 175 Elastic, 157, 197 Elastin, 151, 157, 160 Elective, 97, 157 Electrolyte, 157, 195 Electrons, 30, 142, 145, 148, 157, 171, 182, 183, 189, 190 Elementary Particles, 157, 180, 188 Emboli, 29, 157 Embolization, 29, 157 Embryo, 16, 139, 158, 169, 181, 182 Emetic, 154, 158 Emulsions, 102, 158 Enamel, 158, 172 Encapsulated, 12, 158 Endemic, 23, 138, 158, 193 Endocrine Glands, 158 Endocrine System, 105, 158 Endogenous, 19, 27, 37, 89, 144, 157, 158, 182 Endometrial, 78, 158 Endometrium, 78, 158

209

Endopeptidases, 21, 143, 154, 158, 177, 184, 194 Endoscope, 158 Endoscopic, 53, 54, 158 Endoscopy, 74, 108, 158 Endothelial cell, 11, 158, 161 Endothelium, 158, 180 Endothelium-derived, 158, 180 Endotoxic, 158, 174 Environmental Health, 122, 124, 158 Enzymatic, 20, 141, 147, 148, 152, 159, 177, 187, 191 Eosinophil, 37, 38, 159, 171 Eosinophilia, 39, 159 Eosinophilic, 71, 85, 95, 97, 99, 109, 159 Eosinophilic Gastroenteritis, 71, 159 Eosinophilic Granuloma, 85, 97, 99, 159 Epidemic, 9, 16, 159 Epidermal, 102, 159, 176 Epidermis, 102, 153, 155, 159, 172 Epidermoid carcinoma, 159, 196 Epigastric, 159, 183 Epinephrine, 140, 159, 179, 180, 190 Epistaxis, 159, 188 Epithelial, 6, 18, 29, 139, 159, 190 Epithelial Cells, 18, 29, 159 Epithelioid Cells, 13, 67, 78, 83, 159 Epithelium, 145, 158, 159, 171, 172 Epitope, 32, 159 Erythema, 25, 96, 159, 160 Erythema Nodosum, 25, 96, 160 Erythrocyte Membrane, 58, 160 Erythrocytes, 141, 146, 160, 165, 183, 190 Esophageal, 160, 162 Esophagitis, 160, 162 Esophagus, 4, 156, 160, 162, 174, 185, 191, 196 Ether, 102, 160 Eukaryotic Cells, 160, 169 Evoke, 160, 196 Excisional, 4, 160 Excisional biopsy, 4, 160 Excrete, 13, 160 Exocrine, 160, 183 Exogenous, 157, 158, 160, 163 Expander, 160, 199 External-beam radiation, 160, 172, 189, 203 Extracellular, 21, 143, 153, 160, 161, 170, 176, 195 Extracellular Matrix, 21, 153, 160, 161, 170, 176

Extracellular Matrix Proteins, 160, 176 Extracellular Space, 160, 161 Extraction, 5, 161 Extravasation, 109, 161 Extravascular, 57, 61, 161 Exudate, 37, 161, 181 F Facial, 49, 53, 57, 76, 109, 161, 183 Facial Expression, 161 Facial Nerve, 109, 161, 183 Fallopian tube, 161, 201 Family Planning, 123, 161 Fat, 145, 146, 148, 153, 157, 161, 172, 173, 174, 192, 193, 195, 197 Febrile, 161, 181 Fentanyl, 9, 161 Ferritin, 38, 161 Fibroblast Growth Factor, 20, 161 Fibroblasts, 16, 18, 161, 178, 192 Fibrosis, 12, 13, 19, 20, 22, 26, 56, 161, 189, 193 Fluorescence, 31, 161 Fold, 53, 69, 161, 181 Fossa, 44, 161 Free Radicals, 142, 156, 161 Frozen Sections, 11, 162 Fungi, 162, 177, 179, 196, 202, 203 Fungus, 12, 151, 154, 162, 179 G Gallbladder, 108, 139, 145, 150, 162, 166 Gallium, 84, 162 Gamma Rays, 162, 189, 190 Gamma-interferon, 162, 170 Gas, 155, 162, 167, 180 Gastric, 61, 148, 159, 162 Gastritis, 61, 96, 162 Gastroenteritis, 96, 162 Gastroesophageal Reflux, 5, 162 Gastroesophageal Reflux Disease, 5, 162 Gastrointestinal, 4, 74, 147, 159, 162, 195, 197, 198, 201 Gastrointestinal tract, 162, 195, 198, 201 Gelatin, 102, 162, 164, 197 Gene, 10, 12, 13, 14, 17, 18, 19, 24, 26, 27, 29, 30, 31, 33, 36, 37, 38, 40, 67, 76, 80, 146, 163 Gene Expression, 13, 17, 24, 26, 31, 33, 38, 67, 163 Gene Products, rev, 163 Gene Rearrangement, 76, 163 Gene Targeting, 30, 163 Genes, env, 14, 163

210

Granulomas

Genetic Code, 163, 180 Genetic Engineering, 146, 151, 163 Genetic testing, 163, 187 Genital, 163, 171, 201 Genotype, 15, 163, 185 Giant Cells, 6, 13, 57, 159, 163, 193 Gingival Hyperplasia, 5, 163 Gland, 6, 49, 109, 140, 150, 163, 175, 183, 185, 188, 193, 196, 197, 198, 199 Glomerular, 163, 191 Glomeruli, 163 Glomerulonephritis, 61, 163 Glucose, 149, 155, 164, 165, 170, 192 Glucose Intolerance, 155, 164 Glycerol, 164, 185 Glycerophospholipids, 164, 185 Glycine, 141, 145, 164, 179, 194 Glycols, 164, 167 Glycoprotein, 29, 30, 99, 163, 164, 175, 178, 201 Glycoside, 164, 167, 192 Glycosylation, 29, 164 Gonadal, 164, 196 Governing Board, 164, 187 Grade, 50, 71, 164 Graft, 164, 169 Graft Rejection, 164, 169 Granulation Tissue, 46, 105, 164 Granule, 30, 164 Granulocyte, 26, 38, 164, 171 Growth factors, 20, 165 Guanylate Cyclase, 165, 180 Guinea Pigs, 15, 31, 90, 165 H Habitual, 149, 165 Haploid, 165, 186 Headache, 165, 188, 200 Heart attack, 148, 165 Heart failure, 153, 165, 180, 189 Hematology, 47, 63, 83, 107, 165 Hematopoiesis, 165, 171 Heme, 30, 154, 165 Hemoglobin, 141, 160, 165 Hemolysis, 160, 165 Hemolytic, 49, 165 Hemorrhage, 11, 61, 165, 197, 198 Hemostasis, 165, 170 Heparan Sulfate Proteoglycan, 46, 166 Hepatic Artery, 107, 166 Hepatic Encephalopathy, 107, 166 Hepatitis, 42, 44, 51, 55, 58, 61, 63, 64, 65, 108, 128, 166, 202

Hepatocellular, 42, 62, 70, 107, 166 Hepatocellular carcinoma, 62, 166 Hepatocyte, 150, 166 Hereditary, 3, 103, 149, 166, 185 Heredity, 163, 166 Herpesviridae, 85, 155, 166 Heterodimer, 30, 166 Heterogeneity, 15, 83, 140, 166 Histiocytosis, 4, 38, 69, 109, 159, 166 Histology, 88, 109, 166, 183 Histoplasma, 49, 65, 166 Homogeneous, 15, 166 Homologous, 163, 166 Hormonal, 144, 166 Hormone, 147, 159, 166, 170, 187, 192, 195, 199 Hybrid, 144, 166, 167 Hybridomas, 25, 166 Hydrogen, 102, 139, 147, 148, 155, 160, 167, 174, 178, 180, 182, 188, 197, 199 Hydrogen Peroxide, 102, 148, 167, 174, 197 Hydrolases, 94, 167, 185 Hydromorphone, 9, 167 Hydrophobic, 155, 164, 167, 174 Hydroxides, 167 Hydroxyl Radical, 55, 167 Hydroxylysine, 151, 167 Hydroxyproline, 141, 151, 167 Hyperbilirubinemia, 167, 172 Hypercholesterolemia, 89, 167 Hyperostosis, 109, 167 Hyperreflexia, 167, 198 Hypersensitivity, 10, 20, 29, 41, 42, 86, 89, 159, 167, 192 Hypertension, 78, 148, 165, 167, 187 Hypertrophy, 153, 167, 200 Hypnotic, 145, 167, 198 Hypogammaglobulinemia, 151, 167 Hypothalamus, 167, 185, 195 I Iatrogenic, 59, 167 Idiopathic, 33, 57, 96, 103, 168, 193 Immune function, 19, 168 Immune Sera, 168 Immune system, 14, 17, 142, 144, 146, 157, 168, 169, 175, 185, 203 Immunization, 32, 61, 139, 168, 169 Immunoblotting, 26, 168 Immunocompromised, 17, 168 Immunodeficiency, 50, 151, 167, 168 Immunodeficiency syndrome, 151, 168

211

Immunodominant Epitopes, 32, 168 Immunofluorescence, 11, 72, 168 Immunogenic, 168, 174 Immunoglobulin, 18, 42, 142, 168, 178 Immunohistochemistry, 4, 11, 57, 168 Immunologic, 7, 22, 29, 39, 140, 149, 168, 175, 190 Immunology, 15, 21, 32, 34, 51, 54, 55, 60, 61, 62, 67, 77, 80, 89, 96, 139, 140, 168 Immunomodulator, 27, 168 Immunosuppression, 168, 181 Immunosuppressive, 168, 169 Immunosuppressive therapy, 169 Immunotherapy, 7, 12, 46, 53, 54, 140, 146, 169 Impairment, 13, 145, 150, 169 Implant radiation, 169, 171, 172, 189, 203 Implantation, 152, 169, 181, 199 In situ, 16, 17, 18, 33, 52, 67, 68, 72, 169 In Situ Hybridization, 16, 17, 33, 169 In vitro, 11, 18, 21, 23, 25, 26, 28, 29, 34, 35, 77, 88, 89, 90, 96, 169, 187, 194, 199 In vivo, 10, 11, 17, 18, 23, 24, 27, 29, 31, 34, 35, 88, 96, 169, 182 Incisor, 5, 169 Incompetence, 162, 169 Incubation, 13, 169, 173 Incubation period, 169, 173 Induction, 9, 14, 19, 70, 90, 169 Infancy, 108, 169 Infarction, 153, 169, 177 Infiltration, 7, 69, 159, 163, 169 Inflammatory bowel disease, 18, 67, 170 Infusion, 9, 105, 170 Ingestion, 62, 170, 186 Inhalation, 15, 90, 140, 151, 170, 181, 186, 194, 196 Initiation, 13, 16, 29, 170 Innervation, 161, 170 Insight, 14, 21, 22, 25, 31, 170 Instillation, 79, 170 Insulin, 105, 170, 172 Insulin-dependent diabetes mellitus, 170 Integrins, 18, 170 Intercellular Adhesion Molecule-1, 57, 170 Interferon, 20, 21, 25, 26, 36, 37, 40, 51, 55, 68, 116, 117, 162, 170 Interferon-alpha, 51, 55, 170 Interleukin-1, 18, 37, 40, 68, 170 Interleukin-2, 36, 37, 170, 171 Interleukin-4, 36, 42, 68, 171 Interleukin-5, 36, 171

Intermittent, 171, 184 Internal radiation, 171, 172, 189, 203 Interstitial, 18, 52, 53, 72, 96, 147, 161, 171, 172, 191, 203 Intestinal, 4, 62, 148, 171 Intestine, 145, 147, 171, 172 Intracellular, 8, 14, 16, 17, 29, 36, 40, 103, 169, 170, 171, 176, 180, 190, 192 Intrahepatic, 42, 171 Intramuscular, 48, 171 Intraperitoneal, 45, 60, 171 Intrathecal, 9, 80, 81, 171 Intravenous, 45, 66, 170, 171 Intravesical, 46, 53, 171 Intrinsic, 26, 140, 145, 171 Invasive, 171, 175 Involution, 28, 171 Ionizing, 140, 171, 176, 190 Ions, 156, 157, 167, 171, 183, 195 Iris, 143, 153, 171, 189, 193, 202 Irradiation, 69, 172, 203 Ischemia, 144, 172 ITP, 58, 165, 172 J Jaundice, 108, 167, 172 Jaw Cysts, 46, 172 K Kb, 122, 172 Keratin, 51, 69, 102, 172, 193 Ketoacidosis, 139, 172 Ketone Bodies, 139, 172 Keyhole, 44, 172 Killer Cells, 172 Kinetics, 10, 172 L Laceration, 172, 198 Lacrimal, 161, 172, 189 Lacrimal gland, 172, 189 Lactation, 172, 181 Large Intestine, 4, 148, 156, 159, 171, 172, 190, 194 Laryngeal, 5, 49, 69, 74, 78, 79, 82, 173 Larynx, 5, 173, 200, 203 Latent, 7, 17, 21, 31, 173, 187 Lavage, 24, 48, 173 Leishmaniasis, 32, 40, 72, 173 Lens, 147, 173, 203 Lentivirus, 19, 173 Leprosy, 14, 50, 65, 83, 173 Lesion, 164, 173, 174, 192, 201 Lethal, 97, 173 Leucocyte, 159, 173

212

Granulomas

Leukaemia, 47, 93, 173 Leukemia, 150, 173 Leukocytes, 11, 16, 19, 145, 146, 149, 170, 173, 178, 183, 185, 201 Life cycle, 17, 35, 162, 173 Life Cycle Stages, 35, 173 Ligands, 26, 170, 173, 190 Ligation, 105, 106, 173 Linolenic Acids, 89, 173 Lipid, 8, 30, 35, 88, 89, 158, 164, 170, 173, 174, 182 Lipid A, 8, 88, 174 Lipid Peroxidation, 174, 182 Lipophilic, 103, 174 Lipopolysaccharides, 174 Lipoprotein, 174 Lipoxygenase, 41, 143, 174 Liquor, 174, 189 Liver Transplantation, 64, 80, 174 Lobe, 7, 174, 183 Localization, 23, 32, 66, 67, 71, 168, 174 Localized, 7, 23, 32, 34, 46, 71, 156, 158, 159, 165, 169, 174, 180, 186, 193, 198, 201 Locomotion, 174, 186 Low-density lipoprotein, 46, 174 Lower Esophageal Sphincter, 162, 174 Luciferase, 17, 174 Lumbar, 94, 174 Lupus, 25, 28, 48, 57, 174, 198 Lymph node, 7, 19, 25, 39, 45, 96, 98, 128, 144, 149, 175, 189, 191, 193 Lymphadenitis, 82, 175 Lymphatic, 79, 158, 169, 174, 175, 177, 180, 195, 196, 199 Lymphatic system, 174, 175, 195, 196, 199 Lymphedema, 4, 175 Lymphocyte, 25, 30, 34, 41, 57, 72, 96, 142, 168, 172, 175, 176, 178 Lymphocytic, 75, 175 Lymphocytosis, 47, 175 Lymphoid, 6, 73, 142, 164, 173, 175 Lymphokine, 37, 38, 93, 175 Lymphokine-activated killer cells, 93, 175 Lymphoma, 4, 47, 50, 55, 61, 71, 73, 75, 85, 95, 97, 98, 175 Lymphomatoid Granulomatosis, 95, 175 Lymphoproliferative, 5, 175 Lytic, 175, 194, 202 M Macrophage, 17, 18, 22, 26, 27, 29, 38, 54, 89, 90, 105, 170, 175 Macrophage Activation, 27, 89, 175

Macrophage Colony-Stimulating Factor, 38, 175 Magnetic Resonance Imaging, 107, 175 Major Histocompatibility Complex, 8, 25, 41, 171, 176 Malignant, 45, 54, 76, 85, 95, 98, 108, 139, 166, 175, 176, 179, 190, 193 Malnutrition, 144, 176 Mandible, 3, 48, 176 Manifest, 4, 12, 176 Man-made, 45, 176 Mannans, 162, 176 Matrix metalloproteinase, 21, 95, 176 Maxillary, 4, 5, 176 Mediator, 16, 23, 171, 176 Medical Records, 176, 192 MEDLINE, 123, 176 Melanocytes, 176 Melanoma, 54, 176 Membrane, 30, 46, 143, 149, 150, 152, 160, 173, 176, 178, 184, 185, 186, 191, 203 Membrane Lipids, 176, 185 Memory, 10, 141, 177 Meninges, 149, 157, 177 Meningitis, 83, 177 Menopause, 177, 181 Mental, iv, 6, 122, 124, 152, 156, 169, 177, 188, 189, 201 Mental Processes, 156, 177, 189 Mercury, 45, 54, 94, 177 Mesenchymal, 175, 177 Metalloendopeptidases, 158, 177 Metastasis, 176, 177 Metastatic, 70, 90, 98, 177 MI, 89, 138, 177 Microbiology, 16, 32, 34, 89, 144, 177 Microorganism, 21, 177, 183, 203 Microspheres, 59, 177 Migration, 10, 17, 18, 34, 35, 54, 170, 175, 177 Mineralization, 7, 177 Mitochondrial Swelling, 177, 179 Mitosis, 143, 177 Modification, 30, 141, 163, 178 Molecular, 6, 12, 13, 14, 15, 23, 27, 29, 30, 34, 90, 123, 125, 146, 152, 154, 160, 164, 178, 197, 200, 201 Monitor, 11, 17, 178, 180 Monoclonal, 36, 60, 72, 167, 168, 172, 178, 189, 203 Monoclonal antibodies, 36, 60, 72, 168, 178 Monocyte, 23, 26, 34, 175, 178

213

Monocyte Chemoattractant Protein-1, 23, 178 Monokines, 88, 178 Mononuclear, 36, 39, 40, 89, 164, 175, 178, 201 Morphine, 9, 80, 81, 167, 178, 179, 181 Morphological, 39, 103, 158, 162, 176, 178 Morphology, 11, 165, 175, 178 Mucociliary, 178, 194 Mucocutaneous, 173, 178 Mucolytic, 147, 178 Mucosa, 5, 19, 27, 73, 109, 159, 174, 178 Mucus, 178, 201 Mutagenesis, 31, 178 Mutagens, 178 Mycobacteriosis, 19, 179 Mycosis, 179 Mycotic, 46, 179 Myocardium, 177, 179 Myristate, 26, 179 N Narcotic, 161, 178, 179 Nausea, 162, 179, 188, 201 Necrosis, 7, 37, 42, 52, 143, 169, 177, 179, 188, 192, 193 Neoplasia, 80, 179 Neoplasm, 6, 179, 193, 201 Neoplastic, 6, 105, 166, 175, 179 Nerve, 14, 39, 75, 140, 154, 155, 157, 161, 170, 176, 179, 181, 184, 192, 193, 196, 200, 202 Nerve Growth Factor, 39, 179 Nervous System, 140, 149, 176, 179, 184 Neurons, 23, 155, 179, 198 Neuropathy, 179, 184 Neuropeptide, 23, 179 Neurosecretory Systems, 158, 179 Neurotransmitter, 139, 141, 147, 164, 179, 180, 195, 197 Neutralization, 42, 179 Neutrons, 140, 172, 180, 189 Neutrophil, 170, 180 Niacinamide, 98, 180 Nitric Oxide, 56, 68, 180 Norepinephrine, 140, 179, 180, 190 Nuclear, 26, 28, 48, 157, 160, 162, 163, 176, 179, 180 Nuclei, 140, 157, 163, 175, 177, 180, 181, 188 Nucleic acid, 22, 163, 169, 178, 180 Nucleotidases, 167, 180

Nucleus, 143, 145, 150, 154, 155, 157, 160, 162, 178, 180, 188, 196 O Ocular, 75, 180 Oedema, 94, 180 Oestrogen, 69, 180 Ointments, 181, 183 Omentum, 166, 181 Oncogenic, 170, 173, 181 Oncology, 55, 63, 181, 191 Open Reading Frames, 17, 173, 181 Opiate, 178, 181 Opium, 178, 181 Opportunistic Infections, 19, 181 Opsin, 181, 191, 192 Optic Nerve, 181, 182, 191, 193 Organ Culture, 181, 199 Ornithosis, 104, 181, 188 Orofacial, 4, 5, 76, 181 Ossification, 181, 182 Osteitis Fibrosa Cystica, 109, 181 Osteoclasts, 147, 181 Osteodystrophy, 109, 182 Osteogenesis, 109, 182 Osteogenesis Imperfecta, 109, 182 Osteopetrosis, 109, 182 Osteoporosis, 181, 182 Otolaryngology, 5, 50, 109, 182 Otology, 5, 53, 69, 72, 73, 81, 85, 86, 108, 109, 182 Ovaries, 59, 182, 194, 201 Ovary, 153, 180, 182 Ovum, 153, 173, 182, 187 Oxidants, 102, 182 Oxidation, 30, 139, 142, 143, 154, 174, 182 Oxidation-Reduction, 182 Oxidative Stress, 29, 182 P Pachymeningitis, 177, 182 Paediatric, 52, 82, 182 Palliative, 181, 183, 199 Pancreas, 108, 139, 146, 166, 170, 183, 195, 201 Pancreatic, 162, 183, 188 Pancreatic Juice, 162, 183 Pancytopenia, 48, 183 Papilla, 183 Papillary, 6, 183 Paraffin, 22, 79, 183 Parasite, 23, 32, 40, 183, 193 Parasitic, 23, 32, 39, 60, 183, 192 Parasitic Diseases, 32, 183

214

Granulomas

Paratuberculosis, 33, 38, 77, 183 Parenchyma, 9, 183 Parietal, 183, 184, 186 Parotid, 6, 183, 193 Partial remission, 183, 191 Particle, 90, 176, 183, 200 Particle Accelerators, 176, 183 Patch, 20, 24, 153, 183 Pathogen, 8, 14, 16, 18, 104, 169, 183 Pathogenesis, 5, 9, 12, 14, 17, 21, 24, 26, 34, 46, 183 Pathologic, 12, 16, 22, 33, 77, 84, 143, 146, 153, 167, 183, 184 Pathologic Processes, 143, 184 Pathophysiology, 4, 5, 23, 184 Patient Education, 128, 132, 134, 138, 184 Pelvis, 139, 174, 182, 184, 201 Penis, 184, 201 Peptide, 8, 24, 27, 30, 141, 147, 158, 161, 167, 172, 184, 187, 188 Peptide Hydrolases, 158, 167, 184 Percutaneous, 184, 199 Perforation, 5, 184 Periapical Granuloma, 51, 53, 65, 68, 69, 82, 83, 184 Periapical Tissue, 184 Peripheral blood, 23, 26, 170, 184 Peripheral Nerves, 173, 184 Peripheral Nervous System, 179, 184, 195, 197 Peripheral Neuropathy, 75, 184 Peritoneal, 51, 73, 105, 143, 171, 180, 184 Peritoneal Cavity, 143, 171, 180, 184 Peritoneal Dialysis, 105, 184 Peritoneum, 181, 184 Peroxidase, 12, 143, 174, 185 Peroxide, 102, 185 Petroleum, 183, 185 Phagocyte, 30, 36, 40, 175, 182, 185 Phagocytosis, 31, 35, 106, 185 Pharmaceutical Preparations, 149, 163, 185 Pharmacologic, 154, 185, 200 Pharyngitis, 104, 185 Pharynx, 162, 185 Phenotype, 16, 18, 32, 185 Phorbol, 26, 185 Phospholipids, 58, 161, 174, 176, 185 Phosphoric Monoester Hydrolases, 167, 185 Phosphorus, 147, 185 Phosphorylation, 29, 185

Physiologic, 140, 146, 185, 190 Physiology, 14, 53, 165, 185 Pigment, 176, 185 Pituitary Gland, 161, 185 Placenta, 186, 187 Plague, 186, 200 Plants, 28, 140, 146, 147, 164, 178, 180, 186, 192, 196, 200 Plasma, 4, 25, 30, 74, 142, 147, 149, 160, 162, 164, 165, 166, 186 Plasma cells, 4, 142, 164, 186 Plasmid, 21, 186, 202 Platelet Aggregation, 180, 186 Platelets, 58, 143, 149, 180, 183, 186, 199 Pleated, 172, 186 Pleura, 186 Pleural, 23, 180, 186 Pleural cavity, 180, 186 Pneumoconiosis, 186, 194 Pneumonia, 7, 104, 153, 186 Pneumonitis, 181, 186 Poisoning, 145, 162, 177, 179, 186 Polyarthritis, 41, 186 Polyethylene, 98, 186 Polymerase, 22, 65, 86, 186, 187 Polymerase Chain Reaction, 22, 65, 86, 187 Polypeptide, 141, 151, 187, 195 Polysaccharide, 142, 149, 187 Portal Hypertension, 107, 187 Posterior, 143, 150, 171, 183, 187, 193 Potentiates, 170, 187 Practice Guidelines, 124, 187 Precursor, 18, 157, 159, 180, 187, 200 Predisposition, 103, 187 Prenatal, 158, 187 Preoperative, 81, 187 Prevalence, 5, 22, 104, 187 Primary Biliary Cirrhosis, 78, 80, 108, 187 Primary Sclerosing Cholangitis, 62, 187 Progeny, 15, 187 Progesterone, 56, 69, 187, 196 Prognostic factor, 84, 188 Progression, 7, 15, 24, 31, 141, 188 Progressive, 26, 40, 52, 53, 56, 150, 156, 171, 179, 188, 189, 191, 201 Progressive disease, 26, 188 Proline, 151, 167, 188 Promoter, 9, 188 Prophylaxis, 188, 202 Prostate, 146, 181, 188, 201 Protease, 12, 188 Protein C, 141, 144, 161, 172, 174, 188

215

Protein Kinases, 96, 188 Protein S, 146, 163, 188 Protons, 140, 167, 171, 183, 188, 189 Protozoa, 173, 177, 188, 196, 202 Proxy, 15, 188 Pruritic, 157, 188 Pseudocysts, 172, 188 Psittaci, 104, 181, 188 Psittacosis, 104, 188 Psychic, 177, 188, 193 Psychology, 156, 189 Puberty, 3, 189 Public Policy, 123, 189 Publishing, 5, 35, 189 Pulmonary Artery, 78, 146, 189, 202 Pulmonary Fibrosis, 20, 189 Pulmonary hypertension, 49, 153, 189 Pulmonary Sarcoidosis, 72, 189 Pulmonary Veins, 189 Pulmonary Veno-Occlusive Disease, 69, 189 Pulse, 104, 178, 189 Pupil, 153, 189 Pyogenic, 5, 46, 55, 66, 68, 69, 74, 76, 77, 97, 109, 189 Q Quiescent, 31, 189 R Race, 155, 177, 189 Racemic, 155, 189 Radiation, 104, 157, 160, 161, 162, 168, 171, 172, 176, 189, 190, 203 Radiation therapy, 160, 171, 172, 189, 203 Radicular, 53, 94, 190 Radicular Cyst, 53, 94, 190 Radioactive, 167, 169, 171, 172, 176, 178, 180, 181, 189, 190, 203 Radioimmunotherapy, 190 Radiolabeled, 146, 172, 189, 190, 203 Radiological, 60, 83, 184, 190 Radiology, 49, 60, 63, 66, 81, 82, 108, 190 Radiotherapy, 90, 98, 147, 172, 189, 190, 196, 203 Randomized, 157, 190 Ranula, 109, 190 Reactivation, 7, 21, 26, 190 Reagent, 174, 190 Receptor, 9, 10, 16, 18, 19, 23, 24, 25, 26, 27, 32, 36, 37, 42, 50, 56, 67, 82, 105, 142, 175, 190 Receptors, Adrenergic, 155, 190 Recombinant, 29, 31, 32, 40, 190, 202

Recombination, 163, 190 Rectum, 63, 143, 151, 156, 162, 170, 172, 188, 190, 194, 197 Recurrence, 66, 78, 190 Red blood cells, 160, 165, 190, 192 Reductase, 191, 199 Refer, 1, 109, 147, 151, 162, 174, 180, 190, 191, 200, 202 Reflux, 162, 191 Refraction, 191, 195 Regeneration, 161, 191 Regimen, 157, 191 Regional lymph node, 61, 191 Regurgitation, 162, 191 Reinfection, 104, 191 Relapse, 52, 95, 191 Remission, 33, 190, 191 Renal failure, 43, 191 Research Support, 21, 191 Respiration, 53, 178, 191 Respiratory Burst, 30, 191 Retina, 49, 56, 150, 152, 153, 173, 181, 189, 191, 192, 202, 203 Retinal, 75, 181, 191, 192 Retinol, 191, 192 Retrograde, 171, 192 Retrospective, 68, 82, 192 Retrospective study, 68, 192 Rheumatism, 192 Rheumatoid, 18, 59, 80, 182, 192 Rheumatoid arthritis, 18, 80, 192 Rheumatoid Nodule, 80, 192 Rhodopsin, 181, 191, 192 Rickettsiae, 192, 202 Risk factor, 30, 192 Risk patient, 79, 192 Rod, 144, 192 Ruminants, 33, 192 S Saline, 147, 192 Saliva, 192 Salivary, 6, 49, 109, 155, 161, 192, 197 Salivary glands, 155, 161, 192 Saponins, 192, 196 Sarcoid, 6, 12, 25, 26, 44, 50, 51, 56, 63, 67, 68, 75, 76, 77, 85, 192 Sarcoma, 71, 193 Satellite, 66, 193 Schistosome, 27, 39, 40, 55, 62, 94, 193 Schistosomiasis mansoni, 38, 39, 89, 193 Sclera, 150, 152, 153, 193, 202 Sclerae, 182, 193

216

Granulomas

Scleroderma, 102, 193 Scleroproteins, 172, 193 Sclerosis, 56, 193 Screening, 10, 31, 103, 151, 193 Seborrhea, 102, 193 Sebum, 193 Secretion, 19, 27, 170, 172, 178, 193 Secretory, 148, 193 Secretory Vesicles, 148, 193 Sedative, 145, 155, 193 Sediment, 193 Sedimentation, 25, 193 Seizures, 23, 54, 193 Seminal vesicles, 193, 201 Septic, 143, 193 Sequence Analysis, 26, 193 Sequence Homology, 103, 194 Sequencing, 17, 24, 187, 194 Serine, 158, 194 Serine Endopeptidases, 158, 194 Serologic, 33, 194 Serology, 33, 194 Serum, 25, 37, 85, 99, 140, 142, 151, 168, 174, 194, 201 Sex Characteristics, 180, 189, 194 Shock, 194, 200 Shunt, 49, 194 Side effect, 25, 104, 106, 115, 117, 140, 146, 194, 199 Sigmoid, 74, 194 Sigmoid Colon, 74, 194 Signs and Symptoms, 191, 194 Silicosis, 35, 43, 194 Sinusitis, 104, 194 Skeletal, 194, 195 Skull, 194, 198 Small intestine, 4, 148, 157, 159, 166, 171, 194, 195 Smooth muscle, 20, 178, 194, 197 Sodium, 10, 195, 197, 199 Sodium Channels, 195, 199 Soft tissue, 146, 195 Solid tumor, 141, 195 Solium, 23, 195 Solvent, 102, 139, 164, 195 Somatic, 177, 184, 195 Somatostatin, 23, 27, 41, 67, 195 Specialist, 129, 195 Specificity, 32, 140, 143, 158, 168, 195 Spectrum, 14, 141, 195 Sperm, 106, 150, 195 Sphincter, 173, 195

Spinal cord, 80, 81, 143, 149, 150, 157, 171, 177, 179, 182, 184, 195 Spinal Stenosis, 94, 195 Spinous, 159, 195 Spirochete, 195, 198 Spirometry, 25, 195 Spleen, 19, 42, 155, 175, 193, 196 Splenomegaly, 182, 196 Spores, 151, 196 Sporotrichosis, 67, 196 Squamous, 69, 90, 98, 159, 196 Squamous cell carcinoma, 69, 90, 98, 159, 196 Squamous cells, 196 Stabilizer, 9, 196 Standardize, 26, 196 Steady state, 18, 196 Stellate, 70, 196 Stenosis, 196, 197 Stereotactic, 51, 196 Sterile, 98, 143, 196 Sterilization, 106, 196 Steroid, 25, 145, 180, 192, 196 Stimulant, 29, 196 Stimulus, 20, 157, 170, 196, 199 Stomach, 4, 73, 139, 156, 159, 160, 162, 166, 173, 174, 179, 181, 184, 185, 191, 192, 194, 196 Stool, 151, 173, 196 Strand, 186, 196 Streptococcal, 41, 42, 51, 197 Streptococcus, 197 Stress, 9, 21, 29, 162, 179, 182, 187, 192, 197 Stricture, 108, 196, 197 Stroke, 122, 148, 197 Stroma, 6, 171, 183, 197 Subacute, 169, 194, 197 Subclinical, 169, 193, 197 Subcutaneous, 13, 70, 74, 103, 138, 157, 180, 192, 196, 197 Sublingual, 190, 197 Submandibular, 197 Submaxillary, 49, 190, 197 Subspecies, 195, 197 Substance P, 41, 193, 197 Substrate, 167, 197 Superoxide, 30, 55, 72, 191, 197 Superoxide Dismutase, 72, 197 Suppositories, 163, 197 Suppression, 39, 197 Supraclavicular, 56, 197 Surfactant, 102, 197

217

Sweat, 155, 193, 197, 198 Sweat Glands, 155, 193, 197, 198 Synapse, 140, 198, 200 Syncytium, 163, 198 Synovial, 71, 198 Syphilis, 89, 198 Systemic disease, 108, 198 Systemic lupus erythematosus, 28, 57, 83, 198 Systemic therapy, 99, 198 Systolic, 167, 198 T Talampicillin, 36, 198 Tamponade, 59, 198 Temporal, 10, 13, 33, 42, 46, 108, 109, 198 Testicular, 80, 198 Testis, 180, 198 Tetani, 198 Tetanic, 198 Tetanus, 61, 142, 198 Thalidomide, 25, 198 Therapeutics, 116, 198 Thermal, 156, 180, 187, 199 Thioredoxin, 57, 199 Thoracic, 25, 53, 155, 186, 199 Thorax, 57, 85, 139, 174, 199 Threshold, 167, 199 Thrombocytes, 186, 199 Thrombocytopenia, 49, 199 Thrombosis, 170, 188, 189, 197, 199 Thymus, 41, 168, 175, 199 Thyroid, 147, 199 Tissue Culture, 11, 199 Tissue Expanders, 79, 84, 199 Tissue Extracts, 12, 199 Tocainide, 48, 199 Tolerance, 37, 139, 164, 199 Tomography, 72, 199 Topical, 5, 103, 143, 167, 183, 199 Toxic, iv, 144, 156, 179, 199, 200 Toxicity, 156, 177, 199 Toxicology, 62, 90, 95, 124, 200 Toxin, 21, 142, 156, 158, 198, 199, 200 Toxoid, 61, 142, 200 Trachea, 147, 173, 185, 199, 200 Transduction, 13, 200 Transfection, 146, 200 Transfer Factor, 168, 200 Transferases, 164, 200 Translation, 141, 163, 200 Transmitter, 139, 144, 176, 180, 200

Transplantation, 64, 80, 108, 128, 168, 176, 200 Trauma, 46, 103, 108, 109, 160, 165, 179, 200 Tricuspid Atresia, 153, 200 Tryptophan, 151, 200 Tubercle, 21, 200 Tubercular, 31, 200 Tuberculomas, 53, 200 Tularemia, 8, 200 Tumor marker, 146, 200 Tumor Necrosis Factor, 26, 37, 40, 68, 89, 198, 201 Tumour, 52, 201 Tunica, 178, 201 U Ulcer, 25, 164, 201 Ulcerative colitis, 4, 67, 170, 187, 201 Ultrasonography, 54, 201 Umbilication, 103, 201 Umbilicus, 201 Univalent, 167, 182, 201 Uremia, 191, 201 Ureters, 201 Urethra, 184, 188, 201 Uric, 140, 201 Urinary, 201, 203 Urine, 146, 172, 201 Urogenital, 74, 201 Urogenital System, 74, 201 Uterus, 139, 149, 153, 158, 182, 187, 198, 201, 202 Uvea, 201, 202 Uveal tract, 189, 202 Uveitis, 65, 202 V Vaccination, 32, 41, 84, 202 Vaccines, 7, 8, 202, 203 Vacuole, 81, 82, 202 Vagina, 149, 198, 201, 202 Vascular, 68, 141, 150, 155, 158, 164, 169, 180, 186, 202 Vascular endothelial growth factor, 68, 202 Vascular Resistance, 141, 202 Vasculitis, 61, 75, 79, 80, 141, 202 Vasodilators, 180, 202 Vector, 183, 200, 202 Vein, 108, 141, 171, 180, 183, 187, 193, 202 Venereal, 198, 202 Venous, 107, 180, 188, 200, 202 Ventricle, 144, 153, 167, 189, 198, 200, 202

218

Granulomas

Ventricular, 141, 153, 200, 202 Vestibular, 109, 202 Vestibule, 202 Veterinary Medicine, 123, 202 Viral, 85, 108, 163, 181, 200, 202 Viral Hepatitis, 108, 202 Virulence, 14, 21, 22, 31, 144, 199, 202 Virulent, 7, 8, 22, 202 Virus, 20, 108, 144, 163, 170, 200, 202, 203 Visceral, 40, 64, 72, 85, 173, 184, 203 Visceral Larva Migrans, 64, 203 Vitreous, 173, 191, 203 Vitreous Body, 191, 203 Vitro, 11, 18, 23, 29, 30, 34, 203 Vivo, 9, 10, 17, 18, 23, 29, 39, 203 Vocal cord, 85, 86, 203

W White blood cell, 142, 146, 150, 159, 164, 173, 175, 178, 180, 186, 203 Wound Healing, 102, 161, 170, 176, 203 X Xanthine, 140, 203 Xanthine Oxidase, 140, 203 Xenograft, 141, 203 X-ray, 25, 97, 148, 152, 161, 162, 172, 176, 180, 189, 190, 196, 203 X-ray therapy, 172, 203 Y Yeasts, 162, 185, 203 Z Zebrafish, 16, 203

219

220

Granulomas

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