ATHEROSCLEROSIS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Atherosclerosis: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83749-X 1. Atherosclerosis-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on atherosclerosis. 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 ATHEROSCLEROSIS ................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Atherosclerosis ............................................................................ 12 E-Journals: PubMed Central ....................................................................................................... 72 The National Library of Medicine: PubMed ................................................................................ 77 CHAPTER 2. NUTRITION AND ATHEROSCLEROSIS........................................................................ 107 Overview.................................................................................................................................... 107 Finding Nutrition Studies on Atherosclerosis........................................................................... 107 Federal Resources on Nutrition ................................................................................................. 121 Additional Web Resources ......................................................................................................... 122 CHAPTER 3. ALTERNATIVE MEDICINE AND ATHEROSCLEROSIS ................................................. 127 Overview.................................................................................................................................... 127 National Center for Complementary and Alternative Medicine................................................ 127 Additional Web Resources ......................................................................................................... 135 General References ..................................................................................................................... 145 CHAPTER 4. DISSERTATIONS ON ATHEROSCLEROSIS ................................................................... 147 Overview.................................................................................................................................... 147 Dissertations on Atherosclerosis................................................................................................ 147 Keeping Current ........................................................................................................................ 149 CHAPTER 5. CLINICAL TRIALS AND ATHEROSCLEROSIS .............................................................. 151 Overview.................................................................................................................................... 151 Recent Trials on Atherosclerosis................................................................................................ 151 Keeping Current on Clinical Trials ........................................................................................... 170 CHAPTER 6. PATENTS ON ATHEROSCLEROSIS .............................................................................. 173 Overview.................................................................................................................................... 173 Patents on Atherosclerosis ......................................................................................................... 173 Patent Applications on Atherosclerosis ..................................................................................... 198 Keeping Current ........................................................................................................................ 235 CHAPTER 7. BOOKS ON ATHEROSCLEROSIS .................................................................................. 237 Overview.................................................................................................................................... 237 Book Summaries: Federal Agencies............................................................................................ 237 Book Summaries: Online Booksellers......................................................................................... 242 The National Library of Medicine Book Index ........................................................................... 250 Chapters on Atherosclerosis....................................................................................................... 252 CHAPTER 8. MULTIMEDIA ON ATHEROSCLEROSIS ....................................................................... 253 Overview.................................................................................................................................... 253 Video Recordings ....................................................................................................................... 253 Bibliography: Multimedia on Atherosclerosis............................................................................ 255 CHAPTER 9. PERIODICALS AND NEWS ON ATHEROSCLEROSIS .................................................... 257 Overview.................................................................................................................................... 257 News Services and Press Releases.............................................................................................. 257 Newsletter Articles .................................................................................................................... 261 Academic Periodicals covering Atherosclerosis ......................................................................... 262 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 263 Overview.................................................................................................................................... 263 U.S. Pharmacopeia..................................................................................................................... 263 Commercial Databases ............................................................................................................... 264 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 269 Overview.................................................................................................................................... 269
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NIH Guidelines.......................................................................................................................... 269 NIH Databases........................................................................................................................... 271 Other Commercial Databases..................................................................................................... 273 The Genome Project and Atherosclerosis ................................................................................... 273 APPENDIX B. PATIENT RESOURCES ............................................................................................... 277 Overview.................................................................................................................................... 277 Patient Guideline Sources.......................................................................................................... 277 Finding Associations.................................................................................................................. 282 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 285 Overview.................................................................................................................................... 285 Preparation................................................................................................................................. 285 Finding a Local Medical Library................................................................................................ 285 Medical Libraries in the U.S. and Canada ................................................................................. 285 ONLINE GLOSSARIES................................................................................................................ 291 Online Dictionary Directories ................................................................................................... 293 ATHEROSCLEROSIS DICTIONARY ....................................................................................... 295 INDEX .............................................................................................................................................. 385
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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 atherosclerosis 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 atherosclerosis, 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 atherosclerosis, 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 atherosclerosis. 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 atherosclerosis, 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 atherosclerosis. 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 ATHEROSCLEROSIS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on atherosclerosis.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and atherosclerosis, 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 “atherosclerosis” (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: •
Is Insulin Sensitivity a Causal Intermediate in the Relationship Between Alcohol Consumption and Carotid Atherosclerosis?: The Insulin Resistance and Atherosclerosis Study Source: Diabetes Care. 25(8): 1425=1431. August 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: An association has been demonstrated between alcohol consumption and atherosclerosis. Insulin resistance, also a risk factor for atherosclerosis, has been shown to have a similar association with alcohol intake. This raises the question of whether insulin sensitivity is a causal intermediate in the alcohol-atherosclerosis relationship. This article reports on the Insulin Resistance Atherosclerosis Study, a multicenter cohort
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study designed to investigate relationships among insulin sensitivity, risk factors for cardiovascular disease, and carotid artery atherosclerosis. A J-shaped association was observed between alcohol consumption and common carotid artery intimal medial thickness. The protective aspect of the alcohol-atherosclerosis relationship was attenuated by 25 percent after the adjustment for insulin sensitivity. However, an interaction was observed between alcohol consumption and glucose tolerance (GT) status. In comparison with never-drinkers, all levels of alcohol consumption were associated with less atherosclerosis in participants with normal GT status. Participants with impaired GT status (but not diabetes) demonstrated a J-shaped alcoholatherosclerosis association. All levels of alcohol consumption were association with more atherosclerosis in participants with diabetes. These findings contrast with previous reports and do not support current recommendations regarding moderate alcohol consumption in people with diabetes. The authors call for more research to clarify this issue. 2 figures. 1 table. 43 references. •
Is Atherosclerosis Different in Patients with Type 2 Diabetes?: The Role of Fibrinolysis Source: Practical Diabetology. 20(2): 7-9, 12-14. June 2001. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (212) 989-0200 or (773) 777-6801. Summary: Atherosclerosis and cardiovascular disease in people with diabetes aredifferent from those in nondiabetic persons in several important respects. Mortality (death rate) is higher in patients with diabetes after undergoing percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). A higher rate of re-stenosis after stent placement and compositional differences in atheroma make plaques more subject to rupture and more likely to cause sudden cardiac death in patients with diabetes. A higher level of plasminogen activator inhibitor 1 (PAI 1) in patients with diabetes appears to be one important factor contributing to these differences. This article focuses on the potential role of PAI 1 in atherogenesis (the development of atherosclerosis) and its interaction with other factors associated with diabetes and insulin resistance. Numerous studies have shown that lifestyle modifications and lipid lowering medications yield significant reductions in cholesterol; lipid lowering in turn markedly reduces the incidence of cardiovascular events over a 3 to 5 year period. The author reviews research on the use of insulin sensitizers (drugs) pioglitazone and rosiglitazone as another potential approach to address the pathophysiologic mechanisms in the formation of unstable plaques. Long term studies with insulin sensitizers are needed to determine whether they can in fact reduce cardiovascular mortality and morbidity in patients with type 2 diabetes. 7 figures. 16 references.
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Diabetes and Atherosclerosis: Epidemiology, Pathophysiology, and Management Source: JAMA. Journal of the American Medical Association. 287(19): 2570-2581. May 15, 2002. Summary: Complications of atherosclerosis (fat buildup in the major arteries of the body) cause most morbidity (complications) and mortality (death) in patients with diabetes mellitus. Despite the frequency and severity of disease, proven medical therapy remains incompletely understood and underused. This article reports on a study undertaken to review the epidemiology, pathophysiology, and medical and invasive treatment of atherosclerosis in patients with diabetes mellitus. The authors performed a
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computerized literature search (1976 through 2001); additional data sources included bibliographies of identified articles and preliminary data presented at recent cardiology conferences. Their data synthesis shows that diabetes mellitus markedly increases the risk of myocardial infarction (heart attack), stroke, amputation, and death. The metabolic abnormalities caused by diabetes induce vascular dysfunction that predisposes this patient population to atherosclerosis. Blood pressure control, lipidlowering therapy, ACE inhibitors, and antiplatelet drugs significantly reduce the risk of cardiovascular events. Although patients with diabetes can undergo revascularization procedures because of acute coronary syndromes or critical limb ischemia (lack of blood flow), the outcomes are less favorable in this population than in nondiabetic cohorts. The authors conclude that since most patients with diabetes die from complications of atherosclerosis, they should receive intensive preventive interventions proven to reduce their cardiovascular risk. 2 figures. 3 tables. 168 references. •
Factor Analysis of Metabolic Syndrome Using Directly Measured Insulin Sensitivity: The Insulin Resistance Atherosclerosis Study Source: Diabetes. 51(7): 2642-2647. July 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Factor analysis, a multivariate correlation technique, has been used to provide insight into the underlying structure of metabolic syndrome, which is characterized by physiological complexity and strong statistically intercorrelation among its key variables. This article reports on a study that investigated, using factor analysis, the clustering of physiologic variables using data from 1,087 nondiabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS). This study includes information on the directly measured insulin sensitivity index from intravenous glucose tolerance testing among African-American, Hispanic, and non-Hispanic white subjects aged 40 to 69 years at various stages of glucose tolerance. Factor analysis identified two underlying factors among a group of metabolic syndrome variables in this dataset. Analyses using surrogate measures of insulin resistance suggested that these variables provide adequate information to explore the underlying intercorrelational structure of metabolic syndrome. Additional clarification of the physiologic characteristics of metabolic syndrome is required as individuals with this condition are increasingly being considered candidates for behavioral and pharmacologic (drug) intervention. 6 tables. 38 references.
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Impact of Simultaneous Pancreas and Kidney Transplantation on Progression of Coronary Atherosclerosis in Patients with End-Stage Renal Failure due to Type 1 Diabetes Source: Diabetes Care. 25(5): 906-911. May 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: Mortality (death) in type 1 diabetes patients with end stage renal failure is high and is dominated by coronary (heart) atherosclerotic events. With regard to prognosis, simultaneous transplantation of pancreas and kidney (SPK) may be superior to kidney transplantation alone (KTA) in these patients, because normalization of blood glucose levels may reduce progression of coronary atherosclerosis and because it is well known that progression of coronary atherosclerosis is one of the major factors that determines clinical prognosis. This article reports on a study that compared progression
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of coronary atherosclerosis in patients with (n = 26) and those without (n = 6) a functioning pancreas graft after SPK. Mean follow up was 3.9 years. Average glucose control was significantly worse for the patients without a pancreas graft than for patients with a functioning pancreas graft. Regression of atherosclerosis occurred in 38 percent of patients with a functioning pancreas graft compared with 0 percent of patients in whom the pancreas graft was lost. The authors conclude that this observation is an important part of the explanation for the observed improved mortality rates reported in type 1 diabetes patients with end stage renal failure after SPK compared with KTA. In light of these findings, the authors recommend that SPK be carefully considered for all diabetes transplant candidates. 3 figures. 1 table. 40 references. •
Serum and Dietary Magnesium and the Risk for Type 2 Diabetes Mellitus: The Atherosclerosis Risk in Communities Study Source: Archives of Internal Medicine. 159(18): 2151-2159. October 11, 1999. Contact: Available from American Medical Association. Subscriber Services Center, P.O. Box 10946, Chicago, IL 60610-0946. (800) 262-2350. Fax (312) 464-5831. E-mail:
[email protected]. Summary: This article describes a prospective cohort study that examined the association between serum magnesium level and dietary magnesium intake and the subsequent risk for incident type 2 diabetes in a cohort of 12,128 middle aged adults without diabetes from the Atherosclerosis Risk in Communities Study during 6 years of followup. Fasting serum magnesium level, categorized into six levels, and dietary magnesium intake, categorized into quartiles, were measured at the baseline examination. Incident type 2 diabetes was defined by self report of physician diagnosis, use of diabetic medication, fasting glucose level of at least 7.0 mmol/liter, or nonfasting glucose level of at least 11.1 mmol/liter. The study found that, among white participants, a graded inverse relationship between serum magnesium levels and incident type 2 diabetes was observed. From the highest to the lowest serum magnesium levels, there was an approximately two fold increase in incidence rate. This graded association remained significant after simultaneous adjustment for potential confounders, including diuretic use. Compared with individuals with serum magnesium levels of 0.95 mmol/liter or greater, the adjusted relative odds of incident type 2 diabetes rose progressively across the following lower magnesium categories: 1.13, 1.20, 1.11, 1.24, and 1.76. In contrast, little or no association was observed in African American participants. No association was detected between dietary magnesium intake and the risk for incident type 2 diabetes in African American or white participants. The article concludes that, among white participants, low serum magnesium was a strong, independent predictor of incident type 2 diabetes. That low dietary magnesium intake did not confer risk for type 2 diabetes implies that compartmentalization and renal binding of magnesium may be important in the relationship between low serum magnesium levels and the risk for type 2 diabetes. 1 figure. 5 tables. 52 references. (AAM).
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Markers of Inflammation and Prediction of Diabetes Mellitus in Adults (Atherosclerosis Risk in Communities Study): A Cohort Study Source: Lancet. 353(9165): 1649-1652. May 15, 1999. Contact: Available from Lancet, Ltd. 655 Avenue of the Americas, New York, NY 10010. (212) 633-3800. Fax (212) 633-3850.
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Summary: This article describes a study that investigated whether inflammatory markers predict the development of type 2 diabetes. The study population consisted of 12,330 men and women, aged 45 to 64 years, who were followed for a mean of 7 years. The association between different markers of acute inflammation and subsequent diagnosis of diabetes were analyzed. In a subgroup of 610 individuals selected originally for an unrelated atherosclerosis case-control study, diabetes associations with total sialic acid and orosomucoid, haptoglobin, and alpha1-antitrypsin were also investigated. During the follow-up period, 1,335 new cases of diabetes were detected. Adjusted odds ratios for developing diabetes for quartile extremes were 1.9 for raised white cell count, 1.3 for low serum albumin, and 1.2 for raised fibrinogen. In the subgroup analysis, individuals with concentrations of orosomucoid and sialic acid of more than the median had odds ratios of 7.9 and 3.7, respectively. Adjustment for body mass index and waistto-hip ratio lessened the associations. Those for white cell count, orosomucoid, and sialic acid remained significant. The article concludes that markers of inflammation are associated with the development of diabetes in middle aged adults. Although autoimmunity may partly explain these associations, they probably reflect the pathogenesis of type 2 diabetes. A better understanding of cytokine actions and interactions with other factors in the pathogenesis of type 2 diabetes may lead to improved understanding of its causes and open new approaches for its prevention. 5 tables. 30 references. (AA-M). •
Promise of Primrose? Can Evening Primrose Oil Prevent Nerve Damage and Atherosclerosis? Source: Diabetes Forecast. 52(11): 40-42. November 1999. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article discusses the possible use of evening primrose to help halt or slow the progression of diabetic neuropathy and help prevent atherosclerosis. Evening primrose oil (EPO) contains essential fatty acids. It is about 85 percent linoleic acid by weight and about 10 percent gamma linoleic acid (GLA) by weight. Anti-inflammatory prostaglandins are made from GLA. In people who do not have diabetes, the body converts a portion of linoleic acid into GLA; however, in people who have diabetes, this conversion may be significantly impaired. Taking GLA orally via EPO capsules may help circumvent the decreased production of GLA from linoleic acid. One multicenter study demonstrated that daily use of GLA could improve the symptoms of diabetic neuropathy. In some cases, there can be a reversal of diabetic neuropathy symptoms. Results from the multicenter study also indicate that the best prevention of diabetic neuropathy seems to occur in patients who have the best control of their blood glucose levels. The dosage of EPO to help prevent neuropathy should be about six 500 milligram capsules taken with meals twice daily. EPO could also be a supplement to cholesterol lowering medications. Although there have been no controlled studies on the effect of EPO supplementation on the rate of heart attack in humans, one small study showed that a diet rich in EPO can cause a significant decrease in low density lipoproteins (LDLs). Several studies in animals have shown that EPO reduces the amount of LDLs and serum triglycerides in the blood. There appear to be few if any significant adverse effects of EPO in humans. The drawbacks to using EPO include its cost, which is generally about $50.00 for a 1 month supply, and its lack of regulation by the Food and Drug Administration.
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Intensity and Amount of Physical Activity in Relation to Insulin Sensitivity: The Insulin Resistance Atherosclerosis Study Source: JAMA. Journal of American Medical Association. 279(9): 669-674. March 4, 1998. Summary: This article reports on a study designed to determine whether habitual, nonvigorous physical activity, as well as vigorous and overall activity, is associated with increased insulin sensitivity. The authors note that exercise training is associated with improved insulin sensitivity, but that the potential impact of habitual, nonvigorous activity is uncertain. Participants in this study included 1,467 men and women of African American, Hispanic, and non-Hispanic white ethnicity between the ages of 40 and 69. According to the results of the study, the correlation coefficient between insulin sensitivity and total estimated energy expenditure (EEE) was 0.14 when habitual physical activity was assessed by 1-year recall of activities. The association between vigorous and nonvigorous levels of EEE and insulin sensitivity was weakened after adjustment for the potential mediators, body mass index, and waist-to-hip ratio. Results were similar for subgroups of sex, ethnicity, and diabetes. The results of the study indicate that increased participation in nonvigorous, as well as overall and vigorous physical activity, was associated with significantly higher insulin sensitivity. These findings lend further support to current public health recommendations for increased moderate-intensity physical activity on most days. 6 tables. 40 references. (AA-M).
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Association of Diabetes Mellitus With Coronary Atherosclerosis and Myocardial Lesions Source: American Journal of Epidemiology. 137(12): 1329-1340. June 15, 1993. Summary: This article reports on a study of the predictive relationship between diabetes and autopsy evidence of coronary atherosclerosis and myocardial lesions. Among 8,006 Japanese-American men examined at baseline in 1965-1968 as part of the Honolulu Heart Program, 7,591 were free of cardiovascular disease and 1,515 of these men died over a 17-year followup period. Diabetes status was defined using self-reported history and treatment at several examinations, as well as physician diagnoses during hospitalization between 1965 and 1984. An excess of coronary artery atherosclerosis was present among men with diabetes, but diminished to nonsignificant levels following adjustment for other cardiovascular risk factors. Even after adjustment for other risk factors, myocardial lesions occurred significantly more frequently among persons with diabetes than among nondiabetics. The authors conclude that the more adverse risk factor profile among men with diabetes appears to account for some of the observed excess of coronary atherosclerosis. However, diabetes was independently associated with myocardial lesions suggesting a role for nonatherosclerotic mechanisms, such as clotting abnormalities or microvascular disease, in accounting for the excess clinical heart disease found in persons with diabetes. 3 figures. 4 tables. 69 references. (AA-M).
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Increased Insulin Resistance and Insulin Secretion in Nondiabetic African-Americans and Hispanics Compared With Non-Hispanic Whites: The Insulin Resistance Atherosclerosis Study Source: Diabetes. 45(6): 742-748. June 1996. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 342-2383. Summary: This article reports on a study to compare increased insulin resistance and insulin secretion rates in nondiabetic African Americans and Hispanics compared with
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nondiabetic non-Hispanic whites. Fasting and 2-hour postglucose load glucose and insulin levels, insulin-mediated glucose disposal (insulin sensitivity index), glucose effectiveness, and first-phase insulin response were determined in nondiabetic African Americans 9n=288), Hispanics (n=363) and non-Hispanic whites (n=435). African Americans and Hispanics were more obese than non-Hispanic whites. Both African Americans and Hispanics had higher fasting and 2 hour insulin concentrations and insulin response, but lower insulin mediated glucose disposal, than non-Hispanic whites. These results suggest that greater insulin resistance may be in large part responsible for the higher prevalence of noninsulin-dependent diabetes mellitus (NIDDM) in these minority groups. However, in Hispanics, the greater insulin resistance may be due to greater adiposity and other behavioral factors. 4 tables. 50 references. (AA-M). •
Elevated C-Reactive Protein Associates with Early-Stage Carotid Atherosclerosis in Young Subjects with Type 1 Diabetes Source: Diabetes Care. 25(8): 1432-1438. August 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study undertaken to evaluate whether low grade inflammation contributes to early-stage advanced carotid atherosclerosis in young subjects with type 1 diabetes. The mean and maximum intimal-medial thicknesses (IMT) of the carotid artery were assessed in 55 patients with type 1 diabetes (22 men and 33 women, aged 22.1 years, plus or minus 3.6 years; duration of diabetes 14.2 years plus or minus 5.7 years) and in 75 age-matched healthy nondiabetic subjects (28 men and 47 women). High-sensitive C-reactive protein hs-CRP) levels were also measured. The patients with type 1 diabetes had significantly higher hs-CRP levels as well as significantly higher mean IMT and max IMT than the nondiabetic subjects. Analyses for both diabetic and nondiabetic subjects as a single group showed that hs-CRP levels are independently correlated with the mean IMT and max IMT levels as well as with diastolic blood pressure, sex, and duration of diabetes. The authors conclude that hsCRP levels are elevated in young patients with type 1 diabetes, possibly corresponding with early-stage advanced carotid atherosclerosis. 1 figure. 4 tables. 28 references.
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Stop Atherosclerosis Now Source: Diabetes Forecast. 45(4): 36-38. April 1992. Summary: This article, written for teenagers with diabetes, focuses on the challenge of developing a diet that is low in saturated fats, low in salt, and low in concentrated sweets, but that still meets the demands of a growing body. The author emphasizes the importance of diet in preventing atherosclerosis. Topics include the importance of early vigilance in the war against cholesterol, a discussion of fats and their effects, and ideas to reduce one's risks for atherosclerosis.
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Pathogenesis, Treatment and Complications of Diabetes. A Meeting Report-Part 1: Lipids and Atherosclerosis Source: Practical Diabetology. 10(6): 14-17. November-December 1991. Summary: This first installment in a four-part report presents information from the Scientific and Clinical Program of the 14th International Diabetes Federation Congress that was held in June 1991 in Washington, D.C. This installment focuses on
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hyperlipidemia and the mechanisms of atherosclerosis and diabetes. Speakers at the symposium on hyperlipidemia reviewed the abnormalities in triglycerides and HDL that have now been perceived to be characteristic of diabetes. The reports complemented presentations on the mechanisms of atherosclerosis in diabetes, which focused on modified LDL particles, particularly oxidized and glycosylated LDL, that may be particularly atherogenic and are present in excessive amounts in persons with diabetes. Eight presentations are summarized in this installment. (AA-M). •
Atherosclerosis, Apolipoprotein E, and Prevalence of Dementia and Alzheimer's Disease in the Rotterdam Study Source: Lancet. 349: 151-154. January 18, 1997. Summary: This journal article describes a study of atherosclerosis, apolipoprotein E (apoE), and the prevalence of dementia and its major subtypes Alzheimer's disease (AD) and vascular dementia in a population-based sample of people aged 55 years and older from Rotterdam, the Netherlands. The study sample consisted of 284 patients with dementia (207 of whom had AD) and 1,698 controls without dementia. Carotid artery wall thickness and plaques assessed by ultrasonography and the ratio of ankle to brachial systolic pressure were used as measures of atherosclerosis, and the severity of atherosclerosis was scored on a scale of 0 (no atherosclerosis) to 3 (severe atherosclerosis). ApoE polymorphisms were assessed in 246 dementia patients and 928 controls. All measures of atherosclerosis were significantly associated with all dementia, AD, and vascular dementia. The frequencies of all dementia, AD, and vascular dementia increased substantially with atherosclerosis score. The odds ratio for AD in participants with severe atherosclerosis compared with those without atherosclerosis was 3.0. In participants with the apoE4 gene status and an atherosclerosis score of 2 or 3, the odds ratio for all dementia was 4.5, for AD was 3.9, and for vascular dementia was 19.8. The authors conclude that dementia and its major subtypes AD and vascular dementia are associated with atherosclerosis, and that this association is particularly strong in people with the apoE4 gene status. 1 figure, 3 tables, 29 references.
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Inflammation-Mediated Rheumatic Diseases and Atherosclerosis Source: Annals of the Rheumatic Diseases. 59(5): 321-325. May 2000. Summary: This journal article provides health professionals with information on potential cardiovascular risk factors in systemic lupus erythematous (SLE) and rheumatoid arthritis (RA). Evidence substantiates the observation that young women with SLE or RA are developing atherosclerotic heart disease at higher rates than expected. Classic risk factors for cardiovascular disease in the general population such as hypercholesterolemia, diabetes mellitus, smoking, obesity, hypertension, and a sedentary lifestyle also appear to be important in SLE. Other risk factors for cardiovascular problems in SLE include older age at diagnosis and use or longer use of corticosteroids. Evidence also suggests that having SLE is an independent risk factor for cardiovascular disease. Research on the role of traditional cardiovascular risk factors in the development of atherosclerotic heart disease in RA has not been as extensive as it has been in SLE. The risk of atherosclerosis increases in otherwise healthy postmenopausal women, in part because of the drop in endogenous estrogen levels. However, in both SLE and RA, the abnormalities in sex hormone levels tend toward higher estrogen and lower androgen levels, or both. Although this suggests protection against atherosclerosis rather than increased susceptibility, the protective effect may be offset by the prothrombotic effects of estrogens, particularly in the presence of antiphospholipid antibodies. Another potential disease related or treatment related risk
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factor in SLE and RA is raised serum homocysteine. The link between SLE and RA and atherosclerosis may be the increased expression of cellular adhesion molecules, the recruitment of inflammatory cells, and the lack of appropriate downregulation of proinflammatory processes. The article suggests that future prevention strategies for premature cardiovascular disease in SLE and RA should include a modification of traditional factors plus consideration of anti-inflammatory, immune modulatory, metabolic, and hormonal interventions. 66 references. •
Effect of Fenofibrate on Progression of Coronary-Artery Disease in Type 2 Diabetes: The Diabetes Atherosclerosis Intervention Study, a Randomised Study Source: Lancet. 357(9260): 905-910. March 24, 2001. Contact: Available from Lancet, Ltd. 655 Avenue of the Americas, New York, NY 10010. (212) 633-3800. Fax (212) 633-3850. Summary: This review article describes a study, the Diabetes Atherosclerosis Intervention Study (DAIS), that investigated the effect of fenofibrate on progression of coronary artery disease in type 2 diabetes. DAIS was conducted in 11 clinical centers in Canada, Finland, France, and Sweden. Of the 731 patients screened for inclusion in the study, 418 met the metabolic or cardiac entry criteria. These patients were randomly assigned 200 milligrams per day of micronized fenofibrate or placebo for at least 3 years. They were in good glycemic control, had mild lipoprotein abnormalities, and at least one visible coronary lesion. Half had no previous clinical coronary disease. Initial and final angiograms followed a standard protocol and were analyzed by a computer assisted quantitative approach. Missing data for the primary endpoints were imputed. Analyses were by intention to treat. The study found that total plasma cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein cholesterol, and triglyceride concentrations all changed significantly more from baseline in the 207 participants in the fenofibrate group than in the 211 participants in the placebo group. The fenofibrate group showed a significantly smaller increase in percentage diameter stenosis than the placebo group, a significantly smaller decrease in minimum lumen diameter, and a nonsignificantly smaller decrease in mean segment diameter. The trial was not powered to examine clinical endpoints, but there were fewer in the fenofibrate group than the placebo group. DAIS data suggest that treatment with fenofibrate reduces the angiographic progression of coronary artery disease in type 2 diabetes. This effect is related, at least partly, to the correction of lipoprotein abnormalities, even those previously judged not to need treatment. 4 figures. 2 tables. 30 references. (AA-M).
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Insulin Resistance and Atherosclerosis Source: Diabetes Reviews. 5(4): 331-342. 1997. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This review article evaluates the relationship between insulin resistance and atherosclerosis in people who do not have diabetes. The main goal of the article is to review the risk factors for coronary heart disease (CHD) that occur with increased frequency in insulin resistant people, and to offer pathophysiological explanations for these relationships. The authors point out that CHD is the major cause of morbidity and mortality in people with type 2 diabetes, and that insulin resistance is present in most people who have type 2. Because insulin resistance is so common in people with type 2 diabetes, it is difficult to assess its role in CHD development. Topics include insulin resistance versus hyperinsulinemia; insulin resistance, compensatory hyperinsulinemia,
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dyslipidemia, and CHD; the relationship between hypertriglyceridemia and other risk factors for CHD; and insulin resistance and/or compensatory hyperinsulinemia, hypertension, and CHD. The article notes that the ability of insulin to stimulate glucose uptake varies significantly from person to person. The authors conclude that, at the present time, it is difficult to know if insulin resistance is primarily responsible for accelerating the process of atherogenesis. They also conclude that resistance to insulinmediated glucose disposal and its consequences play a key role in the pathogenesis and clinical course of type 2 diabetes, hypertension, and CHD. 4 figures. 1 table. 90 references. (AA-M). •
Periodontal Disease and Atherosclerosis Source: RDH. 23(1): 52,54,56,58,60,62,64,66. January 2003. Contact: Available from Penwell Corporation. 1421 South Sheridan, Tulsa, OK 74112. Website: www.rdhmag.com. Summary: Total health promotion includes education on reducing the risk factors for periodontal disease, as well as reducing the major controllable risk factors associated with cardiovascular diseases (CVD). Early prevention and intervention can significantly delay the onset of atherosclerosis ('hardening of the arteries') and cardiovascular disease which may result in disability and death from heart attack and stroke. This article brings dental hygienists up to date on the connections between periodontal disease and atherosclerosis. Topics include epidemiology and statistics about CVD and periodontal disease, definitions of atherosclerosis and how it develops, how periodontitis becomes a factor, blood cholesterol, physical inactivity, obesity, lifestyle and lifestyle modification, and the role of dental care providers, including dental hygienists. Dental hygienists can provide enough education so that patients can make informed decisions based on the risk factors identified during their medical history taking. Hygienists can also assist their patients in identifying the major controllable risk factors associated with CVD to establish risk of atherosclerosis and cardiovascular disease and offer suggestions regarding the necessary lifestyle changes to reduce those risks. One figure offers a risk assessment tool for CVD. One sidebar lists recommended Web sites for further information. 1 figure.
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Incident Type 2 Diabetes Mellitus in African American and White Adults: The Atherosclerosis Risk in Communities Study Source: JAMA. 283(17):2253-2259. May 3, 2000. Summary: Using data collected between 1986 and 1989, this study compares the risk of diabetes in African American and white adults between the ages of 45 and 64 and attempts to find explanations for the differences. The authors conclude that middle-aged African Americans are at greater risk of developing type 2 diabetes than middle-aged whites, and have higher blood pressure prior to the development of diabetes. In African American women, but not in men, almost half of this excess risk might be related to modifiable factors, such as overweight.
Federally Funded Research on Atherosclerosis The U.S. Government supports a variety of research studies relating to atherosclerosis. These studies are tracked by the Office of Extramural Research at the National Institutes of
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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 atherosclerosis. 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 atherosclerosis. The following is typical of the type of information found when searching the CRISP database for atherosclerosis: •
Project Title: ACCELERATED PREVALENCE/FACTORS
ATHEROSCLEROSIS
IN
SLE--
Principal Investigator & Institution: Roman, Mary J.; Professor; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) Autopsy and observational data suggest that systemic lupus erythematosus (SLE) is associated with premature atherosclerosis and myocardial infarction; however, clinical studies have reported widely varying event rates, and the prevalence of underlying disease (atherosclerosis and myocardial disease) in SLE patient samples and its relation to that in a control population are unknown. The prevailing hypothesis has been that accelerated atherosclerosis is attributable to an increased frequency of conventional risk factors in SLE patients such as hypertension, hyperlipidemia and obesity, all of which may be provoked or potentiated by therapeutic use of corticosteroids. Alternatively, antiphospholipid antibody (APLA), present in about 20% of the SLE patients, may result in vascular occlusions due to abnormal clotting rather than atherosclerosis; however, data are accumulating that suggest that the inflammatory process per se may be important in the initiation and progression of atherosclerosis. Pilot data for this study indicate that underlying non-invasively- detected atherosclerosis is several-fold more common in patients with SLE in comparison to matched control subjects. Furthermore, left ventricular mass, a marker for and mediator of enhanced cardiovascular morbidity and mortality, is strikingly higher in SLE patients, even after adjustment for differences in body size. Neither of these observations is explained by standard risk factors. Thus, the goals of this project are to: 1) establish the prevalence of atherosclerosis and myocardial disease in an unselected population of SLE patients; 2) compare findings to those in a control population; 3) determine whether the excess prevalence of pre-clinical cardiovascular disease is independent of known cardiovascular risk factors and is additionally related to markers of inflammation and immune system activation; and 4) determine whether atherosclerosis and LV hypertrophy progress more rapidly in SLE patients than in control subjects. Based on preliminary data, the investigators hypothesize that pre-clinical disease will be more common in SLE and will not be fully explained by conventional risk factors for atherosclerosis or thrombosis. They further hypothesize that basic aspects of the inflammatory process (to be partially investigated 2
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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using soluble markers in the current project) are primarily responsible for non-valvular cardiovascular disease in SLE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANDROGENS AND SUBCLINICAL ATHEROSCLEROSIS IN YOUNG WOMEN Principal Investigator & Institution: Siscovick, David S.; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2004 Summary: (provided by applicant): This revised application represents an ancillary study to the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a large cohort study supported by the NHLBI. Several studies have demonstrated crosssectional associations of hyperandrogenism, the primary biochemical feature of clinically-diagnosed polycystic ovarian syndrome (PCOS), with coronary risk factors and atherosclerosis. We propose to examine whether serum androgens, measured earlier in life, and variation in genes related to androgen synthesis, metabolism, and signaling are associated with early-onset subclinical coronary atherosclerosis in young adult women from the community. Additionally, we will examine whether the clinical features of PCOS are associated with subclinical coronary atherosclerosis in young adult women, after taking into account serum androgens. CARDIA provides a unique platform to address these questions; and, the proposed ancillary study will add the laboratory and clinical measurements to CARDIA needed to examine these questions. In the prospective component of the proposed study, we will examine the associations of serum androgens and genetic polymorphisms and haplotypes in ten candidate genes with the presence of coronary artery calcium (CAC) by CT. Androgen and genotyping measures will be made using stored serum and DNA samples collected from 1550 women 5 and 13 years prior to the assessment of CAC at age 33 to 45 years. In the crosssectional component, we will use information collected at a proposed ancillary study visit in Year 16 to examine the associations of the clinical features of PCOS, including the presence of polycystic ovaries detected using trans-vaginal ultrasound, menstrual irregularities, infertility, and hirsutism, with the presence of CAC at Year 15 (n= 1200). Secondarily, we will determine whether longitudinal changes in obesity, physical inactivity, and insulin levels influence the prospective associations of serum androgens and genetic variants in candidate genes with subclinical coronary atherosclerosis. In short, the proposed study addresses a potentially important and relatively unexplored area of investigation related to women's cardiovascular health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANTIOXIDANT AND ANTIINFLAMMATORY MECHANISMS OF HDL Principal Investigator & Institution: Rader, Daniel J.; Director, Preventive Cardiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2007 Summary: (provided by the applicant): High density lipoproteins (HDL) their major protein apoA-I directly protect against atherosclerosis cardiovascular disease, but the mechanisms are not well understood. In addition to its role in reverse cholesterol transport, HDL may have other properties that contribute to its anti-atherogenic effects. We hypothesize that HDL has anti oxidant and anti-inflammatory effects that are relevant and operative in vivo and are important components of the atheroprotective
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effects of HDL. The focus of this proposal is to test this hypothesis using relevant in vivo models in mice and in humans. We will utilize approaches as described in detail in Project 1 (oxidatively modified lipids), Project 2 (nitrated proteins), Project 3 (oxidatively modified extracellular matrix) and Project 4 (oxidative DNA adducts) of this SCOR proposal, to study novel mechanisms by which HDL inhibits atherogenesis. Specific Aim 1: To test the hypothesis that HDL inhibits oxidation of lipids (lipoprotein and plasma membrane), nitration of proteins, oxidative fragmentation of extracellular matrix, and DNA in vitro and to determine the mechanism for these anti-oxidant effects of HDL. Specific Aim 2: To use mouse models of atherosclerosis to determine the effect of both apoA-I deficiency and apoA-1 overexpression on markers of oxidative stress and inflammation in vivo and the relationship to atherosclerosis. Specifically, we will test: 1) that apoA-1 deficiency accelerates the age-related progression of markers of oxidant stress, vascular inflammation, and atherosclerosis; 2) that apoA-I overexpression reduces in vivo oxidant stress and vascular inflammation; 3) that HDL?s effect in increasing prostacyclin is an important in vivo by determining the effect of overexpression of apoA-I on atherosclerosis in the prostacyclin receptor (IP) knockout mouse; and 4) that HDL inhibits atherosclerosis even in the setting of impaired reverse cholesterol transport by determining the effect of apoA-I overexpression on atherosclerosis in SR-BI knockout mice. Specific Aim 3: A prospective observational study will be performed in asymptomatic persons with high HDL-C levels and two comparison groups: individuals with average HDL-C levels and individuals with low HDL-C levels. Baseline markers of oxidant stress and inflammation will be compared among the three groups. In addition, two quantitative measures of subclinical atherosclerosis, carotid intimal-medial thickness (IMT) and coronary artery calcification (CAC) will be determined at baseline. These baseline measures will be repeated at two years. In the three HDL strata, baseline levels of oxidant stress and inflammation will be examined as predictors of progression of atherosclerosis. The experiments proposed will generate substantial insight into the mechanisms by which HDL protects against atherosclerosis, information crucial to the rational development of novel HDL-raising strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: APOLIPOPROTEIN GENES AND ATHEROGENESIS IN ANIMALS Principal Investigator & Institution: Maeda, Nobuyo; Professor; Pathology and Lab Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-APR-1989; Project End 31-MAR-2003 Summary: The long term goal of our research is to develop a deep understanding of the genetic factors underlying atherosclerosis, using mice genetically altered by targeting. The upcoming grant period will take advantage of the predictable development of atherosclerosis in our apolipoprotein E-deficient mice to explore how the atherogenic process is affected by mutations in genes other than those directly involved in lipid metabolism. The genes chosen for study in our three specific aims are each individually important for maintaining vascular health and eanh is a likely candidates for altering the vascular response to elevated levels of plasma lipoproteins. In addition, changes in these genes are likely to make current mouse models of atherosclerosis closer to the human condition. Specific aim 1: We will generate a genetic absence of ascorbic acid (vitamin C) synthesis in mice, by disrupting the mouse L-gulono-gamma- lactone oxidase gene, which humans lost during the evolution. We will combine this with a genetic lack of apoE to test the importance of this dietary antioxidant in the prevention
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of atherosclerosis and in stabilizing atherosclerotic plaques. Specific aim 2: We will test the importance of monocyte recruitment for early lesion development by generating apoE null mice carrying 0, 1, 2, 3, or 4 copies of the chemokine receptor CCR2 gene, coding for the primary receptor for the chemokine MCP-1 (monocyte chemoattractant protein 1). Specific aim 3: We will test the hypothesis that mutations causing elevation in the blood pressures of animals will influence the development, distribution, and the stability of atherosclerotic plaques by combining apoE deficiency with mutations in genes coding for angiotensinogen, endothelial nitric oxide synthase or natriuretic peptide receptor A. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ARGINASE AND NITRIC OXIDE IN ATHEROSCLEROSIS Principal Investigator & Institution: Ignarro, Louis J.; Professor; Molecular & Med Pharmacology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 06-MAR-2001; Project End 31-JAN-2005 Summary: (Verbatim from the application): In the response-to-injury hypothesis of atherosclerosis, numerous factors are involved in atherosclerotic lesions resulting from local injury, including impairment of the arginine-NO pathway. NO and its precursor intermediate, N-hydroxyarginine (NOHA), are potent inhibitors of cell proliferation that interfere with the arginine-polyamine pathway. Deficient production of NOHA + NO may accelerate proliferation of vascular smooth muscle, macrophages and other cells. Arginase is a high turnover enzyme that utilizes arginine to form ornithine + urea. Ornithine is a precursor for polyamines required for cell growth. Elevated arginase activity causes increased conversion of arginine to polyamines at the expense of decreased conversion of arginine to NOHA + NO due to limiting arginine availability. Decreased production of NOHA + NO further amplifies polyamine production due to decreased negative feedback on the arginine-polyamine pathway. Increased arginase expression is characteristic of atherosclerotic lesions and administration of arginase inhibitors to animals with atherosclerosis decreases disease progression. The central hypothesis that drives this proposal is that atherosclerosis is associated with the induction of arginase, leading to increased polyamine production that is further enhanced by diminished production 01 NOHA + NO. The principal objective of the proposed research is to determine whether the increased cell proliferation in atherosclerosis is attributed to increased arginase activity and consequent increased polyamine production coupled to decreased NOHA and NO production. The rationale for this objective is based on our previous findings that NOHA and NO inhibit cell growth by interfering with two sequential steps in the arginine-polyamine pathway. Two specific aims are proposed to address the objective: (a) to elucidate the mechanisms by which increased arginase activity leads to increased cell proliferation, and (b) to determine the effectiveness and mechanisms by which arginase inhibitors slow the progression of atherosclerosis in animal models of atherosclerosis. The feasibility of this approach is borne out by the extensive preliminary data that support the central hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ATHEROGENICITY OF PATHOGENS IN MURINE MODEL Principal Investigator & Institution: Champagne, Catherine M.; Periodontology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599
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Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Human epidemiological studies have shown an association between periodontal and vascular diseases. In parallel, the inflammatory and potentially infectious- nature of atherosclerosis is gaining recognition, suggesting a potential link between infectious diseases, such as periodontitis, and atherosclerosis. However, the effect of periodontal pathogens in atherosclerosis has not been clearly established. The goal of this proposal is to investigate the contribution of oral pathogens to the development of atherosclerotic lesions in a murine model. The apolipoprotein E knockout mouse (ApoE) prone to atherosclerosis will be infected with one recognized human periodontal pathogen in an established model of chronic and localized infection (subcutaneous chamber). Experimental conditions (including power calculations) have been optimized in preliminary studies using this model of infection-enhanced atherosclerosis. Aim 1 will focus on answering the question "could periodontal pathogens contribute to the development of atherosclerotic lesion?" Localized infection will be established by intra-chamber injection of live bacterial cultures of Porphyromonas gingivalis in pre-immunized ApoE mice. Controls will receive medium alone. Two strains of P. gingivalis with varying virulence properties will be tested for their ability to induce an increase in the aorta atheroma lesion size (evaluated at sacrifice by histomorphometry). In parallel, the inflammatory response will be monitored by measuring levels of serum inflammatory cytokines (IL-6 and IL-1 by ELISA) and acute phase proteins (Serum Amyloid A by ELISA). Interaction analyses will be performed to test our hypothesis that infection with P. gingivalis contributes to the development of atherosclerotic lesion by triggering an inflammatory and acute phase response. Aim 2 will address the question "what specific virulence trait(s) expressed by P. gingivalis contribute to the development of atherosclerotic lesion?" Mutants of P. gingivalis for specific virulence factors (Pep0 and FimA,) will be prepared in the most atherogenic strain identified in aim 1 in laboratories. These mutants will be tested in our murine model in regard to atheroma lesion size. In addition, presence of P. gingivalis DNA will be investigated by PCR in descending aorta and liver samples, and serum anti-P. gingivalis antibody levels will be measured by ELISA, to test our hypothesis that specific virulence traits confer to P. gingivalis the ability to evade the host antibody defense system, and reside in organs such as the aorta and the liver. Results from these studies will help in the identification of new targets for atherosclerosis and vascular disease therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ATHEROSCLEROSIS MACULOPATHY
AND
RISK
OF
AGE-RELATED
Principal Investigator & Institution: Cruickshanks, Karen J.; Professor; Ophthalmology and Visual Sci; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2003 Summary: (Applicant's Abstract) The purpose of this epidemiologic study is to evaluate the association of markers of generalized atherosclerosis with the incidence of early and late stage age-related maculopathy in a population-based, nested incident case-control study. This proposal builds on the population-based studies of aging in Beaver Dam, WI: The Beaver Dam Eye Study (EY06594) and the Epidemiology of Hearing Loss Study (AG11099). Participants with incident early age-related maculopathy or incident latestage age-related maculopathy as determined from grading of standardized photographs taken at two examinations five years apart will be eligible as cases for this study. Participants without age-related maculopathy at the time of the 1 0-yr follow-up
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eye examination will be eligible as controls. Incident early cases will be frequencymatched by age and gender to controls using a two-to-one ratio of controls to cases. Incident late age-related maculopathy cases will be frequency-matched to controls by age and gender using a three-to-one ratio of controls to cases. Based on expected 5-yr incidence rates and participation rates in both studies, we estimate that a total of 189 cases with incident early age-related maculopathy and 378 controls and 34 cases with incident late age-related maculopathy and 102 controls will be included in this study. Generalized atherosclerosis will be measured by intima-medial thickness and the presence of plaque in the carotid arteries. Stored videotapes of B mode ultrasound scans of the carotid arteries were obtained as of the Epidemiology of Hearing Loss Study, using a modification of the Atherosclerosis Risk in Communities Study protocol. These scans will be read, and measurements of the intima-medial thickness made, using the Atherosclerosis Risk in Communities ultrasound reading protocol. Age-related maculopathy is well-recognized to be the leading cause of blindness among older adults and a significant public health problem for older adults. As yet there is no way to prevent or effectively treat this disorder. This study will provide important epidemiologic information about the role of atherosclerosis in the etiology of agerelated maculopathy. It takes advantage of an unique opportunity to evaluate this association by utilizing an existing population-based cohort with standardized assessments of the incidence of age-related maculopathy and standardized carotid artery ultrasound scans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ATHEROSCLEROSIS PREVENTION IN MICE BY MUTANT APO A-1 Principal Investigator & Institution: Getz, Godfrey S.; Professor and Chair; Pathology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 01-FEB-1997; Project End 31-JAN-2003 Summary: (Adapted from Investigator's Abstract): An inverse correlation between HDL level and protection against atherosclerosis has emerged from human population studies and the study of transgenic mice. Human HDL is heterogeneous, consisting of two major species, HDL2 and HDL3. In most human population studies, variations in the level of HDL2 have been negatively correlated with atherosclerosis. ApoA-I(Milano) appears to be an exception to the generalization in that modest levels of HDL in these subjects are nevertheless protective, in spite of the fact that HDL3 particles are prominent in these individuals. In this proposal, we will examine the ability of murine and human apoA-Iand apoA-I variants that generate different levels of HDL subclasses to protect against the development of different stages of atherosclerosis (fatty streak lesions and progression to fibroproliferative lesions) and to promote regression of lesions that spontaneously develop in apoE deficient mice. ApoA-I will be introduced into these mice via adenoviral vectors which will allow for the timed expression of apoA-I, as well as manipulation of the amount of protein by varying the dose of virus injected. For long term expression, mice that are deficient in RAG2 as well as apoE are available. Murine and human apoA-I will be compared. Human apoA-I will be expressed in SMC or macrophages (transgenic mice) to assess its impact on atherosclerosis. Other variants will focus on the murine/human chimeric apoA-I and apoA-I(Milano) and related mutants, the latter to assess the importance of heterodimer formation in protecting against atherosclerosis. The influence of human apoA-I and apoA-I variants on atherosclerosis, HDL subclass levels, the ability to stimulate cholesterol efflux and the antioxidant properties of the HDL will be assessed, to attempt correlations among these properties of apoA-I. The Specific Aims are to: 1) determine
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the relative efficacy of murine and human ApoA-1 in the protection against atherosclerosis in apoA/RAG2 double knockout mice; 2) determine the effectiveness of apoA-1 expressed in the vessel wall in protection against atherosclerosis; 3) determine the relative efficacy of apoA-1 (Milano) (Arg 173-Cys) and other mutants of apoA-1 at position 173 on protection against atherosclerosis; 4) determine the relative efficacy of wild type human apoA-1 and a variant of apoA-1 that produces only HDL2 on protection against atherosclerosis; 5) determine if the high level of expression of apoA-1 has the same protective effect on another model of atherosclerosis; and 6) determine if the protective effect of HDL particles relates to their ability to promote cholesterol efflux or to the antioxidant activity of HDL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ATHEROSCLEROSIS, DIABETES AND LPL Principal Investigator & Institution: Semenkovich, Clay F.; Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2002 Summary: Adapted from applicant's abstract): Atherosclerosis is common in humans with diabetes. The underlying mechanisms are not completely clear. Common genetic conditions such as heterozygous LPL deficiency could potentiall be involved. However, the exact role of LPL and atherosclerosis, especially in diabetic patients is uncertain. The long term objective of the application is to understand the mechanisms of premature atherosclerosis in diabetic patients The applicants have generated a mouse with heterozygous LPL deficiency. These heterozygous mice have been crossed with low density lipoprotein receptor knockout mice to generate double knockout mice. The investigators have demonstrated the feasibility of diet-induced atherosclerosis in these models, as well as the production of experimental diabetes. The studies proposed will test the hypothesis that genetic heterozygous LPL deficiency promotes atherosclerosis in diabetes. The application has the following Specific Aims: To determine the effects of the LPL deficient heterozygous state alone and in combination with the LDL receptor deficient phenotype on atherosclerosis in mice with streptozotocin-induced diabetes used as a model for Type-I diabetes. To define how the LPL deficient heterozygous state interacts with streptozotocin-induced diabetes to affect vascular wall gene expression and lipoprotein biology. To determine the effects of the LPL heterozygous deficient state alone and in combination with the LDL receptor knockout phenotype on atherosclerosis in mic with dietary-induced diabetes used as a model for Type-II diabetes. To define how the LPL heterozygous deficient state interacts with this model of diabetes to affect vascular wall gene expression and lipoprotein biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOLOGY OF 12-LIPOXYGENASE ISOZYMES Principal Investigator & Institution: Funk, Colin D.; Professor of Pharmacology; Pharmacology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Atherosclerosis, chronic inflammatory process progressing from fatty lesions to fibrous and unstable plaques, is the major underlying factor in most cases of coronary heart disease. Clinical disease as a result of atherosclerotic disease remains as the leading determinant for the extensive mortality and morbidity. and exorbitant health care costs in our society. The "LDL oxidation" hypothesis has gained general acceptance as a leading player in atherogenesis and it is recognized that oxidized LDL exhibits
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Atherosclerosis
many pro-atherogenic properties. properties. The factors that initiate LDL, oxidating in vivo are poorly understood. However, circumstantial evidence has placed the 12/15lipoxygenase in the context of atherosclerosis. Thus, in the first specific aim, the role of 12/15- lipoxygenase in mouse models of atherosclerosis (apoB editing catalytic polypeptide-1 (apobec-1)/LDL-receptor deficient and apoE deficient) will be assessed by quantitating lesion development throughout the aorta by the "en face" method using appropriately crossbred 12/15-lipoxygenase deficient mice. The combined effects of the anti-oxidant vitamin E with 12/15-lipooxygenase deficiency will also be examined. Total cholesterol, triglycerides, lipoprotein profiles and oxidative stress markers known as isoprostanes will be measured and correlated with lesion development. If specific 12/15-lipoxygenase inhibitors are ultimately to be used in atherosclerotic disease management they will need to be effective in limiting, or causing regression of, preexisting lesion. By using an inducible 12/15-lipoxygenase gene disruption strategy in mice with atherosclerosis at various stages this important matter will be addressed. In specific aim 2, the subset of macrophages expressing 12/15- lipoxygenase will be characterized and purified. The effects of lipid loading and factors regulating 12/15lipoxygenase gene expression will be determined. In specific aim 3, the novel 12(R)lipoxygenase will be characterized and its relevance to atherosclerosis and LDL oxidation discerned. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CD1-RESTRICTED T CELL RESPONSE IN ATHEROSCLEROSIS Principal Investigator & Institution: Geng, Yong J.; Assistant Professor; Medicine; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): The cluster of differentiation I (CD1) proteins represent a new class of antigen-presenting molecules, which structurally resemble MHC class I antigens and may restrict certain T lymphocyte responses to lipid antigens. There are two groups of CD1 molecules encoded by five CD1 genes (CD1a, b, c, d and e). Atherosclerotic lesions contain numerous T cells and CD1-positive macrophages and dendritic cells in addition to chemically modified lipids (e.g., cholesterol oxides or oxysterols and oxidized phospholipids) present in oxidized lipoproteins, raising the possibility that CD1-restricted T cells may exist in the lesions and respond to atherogenic lipid antigens presented by local macrophages and dendritic cells. The specific aims of this proposal are to determine (1) the CD1 isotype expression and CD1restricted T cell response to lipid components of oxidized lipoproteins in atherosclerosis; (2) the association of an CD1 mutation or polymorphism with altered vascular autoimmunity in patients with SLE and atherosclerosis; (3) the cytokine production and pro-apoptotic function of CD1d-restricted NK T cells that are reactive to lipid antigens; and (4) the impact of knocking out CD1d gene on the T cell responses to lipid antigens and the development of atherosclerosis caused by apolipoprotein-E deficiency. The experimental procedures involve the analysis of T cell cytokine production and antigen receptor profiles, the evaluation of T cell response to CD1- lipid complexes, the assessment of genomic DNA sequences for CD1 genes, and the histopathological characterization of atherosclerotic lesions in the CD1/apolipoproteinE double knockout mice recently established in our lab. Accomplishment of this project is anticipated to generate valuable information that help understand the immune mechanisms underlying vascular injury during atherogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CELLULAR CALCIFICATION
/MOLECULAR
MECHANISMS
OF
21
VASCULAR
Principal Investigator & Institution: Bostrom, Kristina I.; Assistant Professor of Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: This Project is focused on understanding the molecular mechanisms involved in vascular calcification and osteoporosis. Matrix GLA protein (MGP) was strongly implicated in the pathogenesis of vascular calcification when an MGP knockout mouse was found to have extensive vascular calcification. Based on this mouse model, MGP might be thought to be an inhibitory factor in vascular calcification. However, in calcified lesions of mice that have a normal MGP gene and in human lesions, MGP expression is postively correlated with the degree of lesion calcification. During the current grant period we demonstrated that MGP regulates bone morphogenetic protein (BMP-2), During the next grant period we will determine the molecular basis for the regulatory role of MGP in the artery wall and its interaction with BMP-2. Other work from this Project during the current grant period provided important clues as to why many patients with progressive vascular calcification also have progressive osteoporosis. Oxidized lipids were shown to promote calcification of calcifying vascular cells (CVC) but inhibited the osteoblastic differentiation and mineralization of marrow stromal cells that are the precursors to mature bone osteoblasts. This was true whether the oxidized lipids were added in vitro or were produced by feeding atherosclerosis suceptible C57BL/6J (BL6) mice an atherogenic diet. These oxidized lipids were also shown to promote osteoclastogenesis and osteoclast activation in vitro. In vivo, feeding an atherogenic diet to atherosclerosis susceptible BL6 mice produced a dramatic reduction in bone mineral density and bone mineral content. Feeding an atherogenic diet to atherosclerosis resistant C3H/HeJ mice causes the same degree of hyperlipidemia as in BL6 mice, but there was no significant reduction in either bone mineral density or bone mineral content in the C3H/HeJ mice. In the next grant period we propose to determine the molecular mechanisms for these observations and we will determine if high density lipoproteins (HDL), components of HDL, and mimetics of HDL will protect against bone loss in mouse models of atherosclerosis. These studies may identify potential new therapeutic targets in vascular calcification and osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHARACTERIZATION OF FORTILIN, A NOVEL ANTI-P53 PROTEIN Principal Investigator & Institution: Fujise, Kenichi; None; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by the applicant): Atherosclerosis is the leading cause of coronary artery disease, peripheral vascular disease and cerebrovascular disease in this country, afflicting millions of Americans. The pathogenesis of atherosclerosis is complex, yet dysregulated proliferation of smooth muscle cells is implicated as an important proponent. A genetic study using p53 knockout mice suggested that he presence of functional 053 is preventive against atherosclerosis in a hyperlipidemic environment. In addition, studies have indicated that the presence of p53 inhibitors, such as Mdm-2 and IE84, accelerates atherosclerosis. Our laboratory identified a new p53 inhibitor and designated it as fortilin. Characterization of fortilin in our laboratory so far showed: (1) The peptide sequence of fortilin is highly conserved among different species. (2) The
22
Atherosclerosis
message of fortilin is resent in all normal human tissues while its expression is greater in cancerous cell lines. (3) Fortiin expression is more prominent in malignant than I benign tissue. (4) Fortilin binds p53. (5) The overexpression prevents of fortilin prevents cells from undergoing etoposide-induced apoptosis. (6) The over expression of fortilin prevents cells from undergoing apoptosis induced by the expression of p53. (7) The overexpression of fortilin inhibits p53-mediated transactivation of BAX, a pro-apoptotic molecule. (8) The expression of fortilin is up regulated in atheroma. There are three major Specific Aims proposed to further characterize fortilin and the fortilin-p53 interaction: Aim 1: To define the region of fortilin that interacts with p53 and other molecules. We will first determine which domain of fortilin participates in p53 binding by generating and evaluating various deletion mutants for their ability to interact with fortilin (Aim1.1). We will then identify the region of that fortilin domain that is required for the interaction with p53 (Aim1.2). Finally, we will establish whether fortilin is covalently modified by sentrin and other ubiquitin-like molecules (Aim 1.3). Aim 2: To characterize the region of p53 that interacts with fortilin and other molecules. In this major aim, we determine which domain (Aim 2.1) and region (Aim 2.2) of p53 participates in fortilin binding, using deletion and point mutants, respectively. We will then evaluate whether the fortilin-binding region of p53 is required for p53 to interact with Mdm2, Mdm-X and BRCA2, p53 binding and inhibitory molecules (Aim 2.3). Aim 3: To investigate the regulatory role of fortilin-p53 interaction in apoptosis. We will determine whether fortilin inhibits p53-mediatd apoptosis (Aim3.1), p53-mediated transactivation of Bax (Aim 3.2) and p53 binding to the Bas-responsive element (Aim 3.3) THROUGH ITS DIRECT binding of p53. Knowledge gained I this proposal will enable us to have a solid foundation for the future intervention of human atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOKINE RECEPTOR ANTAGONISTS IN INFLAMMATORY DISEASE Principal Investigator & Institution: Shahrara, Shiva; Medicine; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): There are many similarities in inflammatory responses observed in atherosclerosis and rheumatoid arthritis (RA). Chemokines and their receptors are important in both diseases. The long-term objectives of this application are to study the clinical and biological effects of C-C chemokine receptor 2 (CCR2) and CCR1/CCR5 antagonists in rodent arthritis. Furthermore we plan to determine the effect of key proinflammatory (TNF-alpha and IL-1beta) and Th1 promoting (IL-12 and IL-18) cytokines on CCR5 and CCR2 post-receptor signaling events in the 2D61L-12 T cell line and endothelial cells in the presence of CCR5/CCR2 antagonists. Using CCR2/CCR5 antagonists in a model of inflammatory disease (RA) in vivo in addition to the knowledge acquired from studying the mechanism of proinflammatory cytokines effects on CCR2/CCR5 signaling pathways in vitro will help us understand and design more efficient in vivo studies in both RA and atherosclerosis. Several studies have used antagonists, binding proteins and antisense sequences to target proinflammatory cytokines, including TNF-alpha (antagonist; Etanercept), IL-18 (binding protein) and chemokine receptors CCR2/CCR5 (antagonists, antibodies and gene knockouts) in hope of mitigating the inflammatory reaction in atherosclerosis and RA. In order to investigate the effect of IL-12 and IL-18 on CCR5 and the effect of TNFalpha, IL-1beta and IL-8 on CCR2 downstream signaling pathways, we will
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immunoprecipitate CC chemokine receptors in cytokine treated cells and detect associated pathways by Western blot analysis. The purpose of using CCR antagonists is to validate that the cytokines exert their effect through these receptors. Additionally we will use CCR2/CCR5 antagonists in an in vivo inflammatory model of RA (rat adjuvant induced arthritis (AIA)) to examine their ability to decrease the severity and delay the onset of the disease. For this purpose we will determine the progression of indicators of inflammation, such as arthritis index, joint circumference, paw volume, joint count, arthritis severity, cell type recruitment and markers of bone destruction. Achieving these goals may give us valuable information in regard to molecular inflammatory mechanisms involved in atherosclerosis and RA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHLAMYDIA ATHEROSCLEROSIS
PNEUMONIAE
AND
MACROPHAGES
IN
Principal Investigator & Institution: Byrne, Gerald I.; Professor & Chairman; Medical Microbiol & Immunology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 15-FEB-1999; Project End 31-JAN-2004 Summary: (Adapted from the Applicant's Abstract): Chlamydia pneumoniae, a causative agent in human community acquired pneumonia, also has been implicated in a variety of sequelae associated with chronic disease and re-exposure to the organism. One important sequel associated with C. pneumoniae infection is the development of atherosclerotic lesions that define the pathology of cardiovascular disease in people. Cardiovascular disease due to atherogenic processes is a major health problem in most of the world, accounting for about 50% of all deaths. It is clear that vascular injury is crucial in the development and progression of atherosclerosis and that this injury can result from a variety of causes, including infection. Several lines of evidence support the hypothesis that C. pneumoniae infection is linked to the development of atherosclerosis. Initially, seroepidemiological evidence was generated to establish a relationship between C. pneumoniae and cardiovascular disease. Subsequently, evidence for the presence of the organism in atherosclerotic lesions was obtained using either direct antigen detection methods or probes specific for C. pneumoniae nucleic acids. In addition, the organism has been isolated from an aortic lesion and grown in cell culture. Finally, two pilot secondary prevention antibiotic treatment trials have provided evidence to suggest that treatment of C. pneumoniae in individuals with coronary heart disease significantly reduces cardiac events in treated versus placebo administered populations. Thus, although the association of C. pneumoniae and atherosclerosis is well-established, existing data do not prove an etiology or pathogenic role for the organism in disease, although both rabbit and murine animal models have been developed to determine if C. pneumoniae is causally associated with development or progression of atherosclerotic lesions in vivo. Activation and modification of mononuclear phagocyte function is associated with atherosclerotic lesion development. Characteristic changes include development of cholesteryl ester-laden monocytes (foam cells) and oxidation of lipids to form tissue-damaging derivatives. The hypothesis to be tested here is that infection of human monocytes, monocyte-derived macrophages or murine monocyte cell lines with C. pneumoniae results in changes in macrophage morphology and function that are consistent with a role for C. pneumoniae in the pathogenesis of atherosclerosis. This hypothesis will be tested by determining if C. pneumoniae causes mononuclear phagocytes to form foam cells in the presence of low density lipoprotein (LDL) or other cholesterol-containing serum lipoprotein complexes.
24
Atherosclerosis
Studies also will be conducted to determine if C. pneumoniae contributes to the oxidative modification of LDL and molecular characterization of C. pneumoniae antigens involved in these processes will be identified. Finally, a murine model will be developed to provide in vivo correlates to cell culture observations. Results will help establish links between C. pneumoniae infection and the atherosclerotic disease process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLONING AND CHARACTERIZATION OF ATH8 Principal Investigator & Institution: Paigen, Beverly J.; Senior Staff Scientist; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: The mouse model of atherosclerosis can be used to identify novel genes that affect atherosclerosis susceptibility. Non-lipid risk factors are important in heart disease but it is difficult to identify the genes that underlie such factors. One approach to identifying such factors to clone the genes underlying atherosclerosis differences between mouse strains that can not be explained by the lipid profiles. Ath8 is such a gene; it is the major determinant of the atherosclerosis susceptibility difference between inbred strains NZB/BINJ (NZB) and SM/J (SM). Although strains NZB and SM differ in HDL-cholesterol and VLDL-LDL cholesterol, Ath8 affects atherosclerosis independently of these lipoprotein differences. The identify of the Ath8 gene product may therefore provide insights into the non-lipid factors that affect heart disease risk. Ath8 was mapped recent in our laboratory using quantitative trait loci mapping techniques. We propose to positionally clone Ath8. Because Ath8 was mapped in a relatively small cross, the chromosomal region containing the gene is large, approximately 28 cM. Therefore, the first step in cloning this gene will be to narrow the region by three sequential mouse crosses. Once the region is sufficiently narrowed, a DNA contig will be constructed and a complete transcript map of all genes in the region obtained. Transcripts will be evaluated by expression patter and function, if known. Candidate genes will be tested by sequence the cDNA from both strains or by expression differences between the strains. Finally, the most compelling candidate gene will be tested by transgenic rescue of the phenotype or construction of a knockout with a resulting change in atherosclerosis phenotype. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COMPLEMENT, CARDIOVASCULAR DISEASE, AND SLE Principal Investigator & Institution: Ahearn, Joseph M.; Associate Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Inflammation is now recognized as a critical process in the development and rupture of atherosclerotic plaques, and in the morbidity and mortality that result from cardiovascular disease. Recent studies have also suggested that this process may be accelerated and exaggerated in patients with systemic lupus erythematosus. We have recently established a research program focused on vascular biology and pathology, with a focus on lupus as a model of accelerated atherosclerosis. The stimulus for these investigations was a recent surprising observation by Manzi and colleagues who demonstrated a strong linear association between elevated serum levels of C3 and C4 and aortic stiffness in premenopausal women with SLE. Whereas decreased serum levels of C3 and C4 have traditionally been used to monitor disease activity in patients with SLE, association of elevated serum levels of serum complement
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components with any disease process is unprecedented. This observation led us to investigate the potential role(s) for complement C3 and C4 in the immunopathogenesis of cardiovascular disease in SLE. Vascular imaging studies led to several intriguing and unexpected observations that will be further explored here. First, we discovered that complement components C3 and C4 are present in several distinct patterns within the arterial walls of both humans and mice. Specifically, proteolytic fragments of C3 and C4 co-localize with, and may be covalently bound to, elastin within the arterial wall. This entirely unexpected observation suggested that complement deposition within the arterial wall may increase vascular stiffness, an early event in atherosclerosis, through direct interference with elastic fiber flexibility. Second, we observed aggregates of complement deposition within the vessel wall, the site at which plaque formation is now known to initiate. Third, we demonstrated that complement components are specifically present within the vasculature of mice with lupus-like syndromes as compared with controls. These observations, together with those of Manzi and colleagues, have led to the following specific aims that are based on our central hypothesis that the complement system may influence vascular stiffness and contribute significantly to the atherosclerotic process by directly reducing vascular elasticity within the arterial wall. The long-term goal of this proposal is to perform an initial characterization of the role of the complement system in atherosclerosis, using normal and abnormal human and mouse vascular systems. Specific Aim 1 is to characterize the spatial and temporal localization of complement proteins C3 and C4 within the arterial wall. Specific Aim 2 is to characterize the distribution of complement C3 and C4 within the arterial tree. Specific Aim 3 is to determine the capacity of complement C3 and C4 within the arterial wall to increase arterial stiffness. These studies will represent the first rigorous investigation of the role of the complement system in atherosclerosis, using SLE as a model of accelerated coronary vascular disease. Ultimately, the data generated by the proposed studies should identify therapeutic targets in SLE and in atherosclerosis in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORONARY ATHEROSCLEROSIS
ARTERY
DYNAMIC
GEOMETRY
AND
Principal Investigator & Institution: Friedman, Morton H.; Professor; Biomedical Engineering; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: The long-term objectives of this research are: (1) to identify geometric features of the vasculature that enhance arterial susceptibility to atherosclerotic disease and can be used for early identification of individuals accordingly at risk, and (2) to understand the role of mechanical factors in the localization and pathobiology of atherosclerosis. To achieve the first objective, relationships are sought between in vivo measurements of the geometric features of human coronary arteries and the pathology of the vessels, with a focus on the early lesion. The second objective is furthered by computing the distribution of fluid dynamic and intramural stresses in selected vessel segments, and seeking correlations between these variables and the thicknesses of the vascular intima and media, as measured in vivo. Clinical biplane coronary cineangiograms of sixty patients at The Ohio State University and Wake Forest University School of Medicine will be processed digitally to reconstruct the threedimensional (3-D) course of the medial axes of selected segments of the left anterior descending and right coronary artery trees. Quantitative geometric parameters of the segments, including both static and dynamic measures of arterial geometry and
26
Atherosclerosis
measures of vessel kinematics, will be obtained from the axes using objective computer algorithms. Variations in geometry among individuals will be assessed. Intravascular ultrasound (IVUS) records of the same segments will be obtained and processed to yield detailed measurements of vessel morphometry collocated to the vessel axes. Doppler flow data and phasic pressure will also be acquired. Relations will be sought between the geometric variables from the angiograms and morphometric parameters derived from the IVUS records; and analysis will take into account individual variability with respect to the traditional risk factors for atherosclerosis. The dynamic data from the angiograms will be used in model calculations to estimate the effect of vessel motion and bending on the flow fieled and wall stresses. For twelve cases, the angiographic and IVUS records will be used to describe the 3-D lumen and wall of a portion of the vessel in diastole. The flow fieled and wall stresses in this region will be simulated numerically, using the Doppler and pressure data as input; the first flow calculation will be validated experimentally. By comparing the computed distribution of stresses acting on and in the vessel segment against that of intima/media thickness, inferences will be drawn regarding the role of mechanical forces in relation to human atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DENDRITIC CELL MIGRATION IN ATHEROSCLEROSIS Principal Investigator & Institution: Randolph, Gwendalyn J.; Assistant Professor; Inst/Gene Therapy & Mol Med; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): During initiation of immune responses, dendritic cells migrate from sites of antigen capture to the T cell zones of lymphoid organs to activate antigen-specific T cells. It remains to be determined whether dendritic cells that enter or develop within atherosclerotic plaques migrate from the plaques, and if so, whether T dependent immune responses that may thereby develop against plaque antigens lead to progression of atherosclerosis. In contrast to our incomplete state of knowledge regarding the role of dendritic cells and T cells in atherosclerosis, evidence that macrophages are involved in the initiation and progression of atherosclerotic lesions is quite strong. Monocytes are well known as the precursors for macrophages, but monocytes can also become dendritic cells in vitro, when cultured with specific exogenous cytokines or when cocultured with endothelial cells, and in vivo. In both human and mouse models, the capacity of monocyte-derived cells to leave tissues is associated with their development into dendritic cells, giving rise to the hypothesis that differentiation of monocytes into dendritic cells may favor their clearance from atherosclerotic plaques. Taking this view, development of dendritic cells from monocytes within the plaque would tend to promote regression. On the other hand, the migration of monocyte-derived dendritic cells from atherosclerotic plaques may favor the development of T-dependent immune responses that potentially mediate the progression of lesions. Our preliminary evidence indicates that monocyte-derived dendritic cell migration is impaired greatly in apoE-deficient mice, supporting the former hypothesis. In the present study, we will further characterize the status and function of dendritic cells in apoE- and LDL receptor-deficient mice. Then we will study whether monocyte and macrophage-derived cells migrate from atherosclerotic lesions during regression of plaques and what routes of migration they may take. The phenotype of any such migrating cells will be assessed, particularly with regard to whether emigrating cells have developed into dendritic cells. The significance of migration from the plaques will be investigated using apoE-/- mice that are deficient in
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molecules that mediate migratory clearance of dendritic cells from tissues. The long term goal of this work is to define how antigen presenting cells, particularly those derived from monocytes, participate in progression and regression of atherosclerosis, with a view toward understanding how manipulating the function of these cells may favor regressive disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIFFERENTIAL MECHANISM OF BAROREFLEX DYSFUNCTION IN ATHEROSCLEROSIS AND AGING Principal Investigator & Institution: Chapleau, Mark W.; Associate Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 21-JAN-2003; Project End 31-DEC-2007 Summary: Compelling evidence implicates reactive oxygen species (ROS) in causing neuronal and cardiovascular dysfunction in atherosclerosis and aging. The goals of the proposed project are to define the role of ROS in causing baroreflex dysfunction in these states and to determine effects of combined atherosclerosis and aging on baroreflex sensitivity. The first hypothesis to be tested is that ROS impair baroreflex function through differential effects on afferent and central components of the reflex. The defect may be primarily in the afferent limb in atherosclerosis, whereas both components may be impaired in aging. The relative importance of alterations in afferent and central components of the baroreflex in atherosclerotic and senescent mice will be determined through direct recordings of aortic depressor nerve activity, renal sympathetic nerve activity, arterial pressure and heart rate; and measurement of responses to drug-induced changes in arterial pressure and electrical stimulation ofbaroreceptor afferents in the aortic depressor nerve. The role of ROS will be assessed through treatment with membrane permeable superoxide dismutase/catalase mimetics and by studies of genetically-modified mice deficient in antioxidant molecules (e.g. MnSOD and CuZnSOD) and transgenics that over-express antioxidant enzymes. The second hypothesis to be tested is that the mechanism of the ROS-mediated decrease in baroreceptor sensitivity differs in atherosclerosis and aging. Vascular NAD(P)H oxidase is proposed as the source of ROS in atherosclerosis while mitochondria in baroreceptors are proposed as the source in aging. Studies in genetically-modified mice, adenoviralmediated gene transfer, and pharmacological antagonists will enable selective manipulation of ROS in subcellular compartments in specific cell types to reveal the sources of ROS generation. Furthermore, neuronal ROS generation and its effects on membrane excitability and ionic currents will be directly assessed in studies of cultured baroreceptor neurons isolated from control, atherosclerotic and senescent mice. The proposed studies are expected to have important implications for understanding mechanisms of baroreflex dysfunction in patients with atherosclerosis and in the elderly. The results may be particularly relevant to humans where atherosclerosis is common in the elderly. Antioxidant therapies are currently receiving much attention as promising agents in the prevention and treatment of cardiovascular disease. Knowledge gained from the proposed studies may impact on future use of antioxidant therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECT ATHERSCLEROSIS
OF
HIGH
DOSE
VITAMIN
E
ON
CAROTID
Principal Investigator & Institution: Jialal, Ishwarlal; Chair; Pathology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105
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Atherosclerosis
Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-MAY-2002 Summary: Cardiovascular disease is the leading cause of morbidity and mortality in Westernized populations. Thus, the role of dietary micronutrients in decreasing LDL oxidation assumes considerable significance. The most consistent data with respect to micronutrient antioxidants and atherosclerosis appears to relate to alpha-tocopherol (AT), the predominant lipid-soluble antioxidant in LDL. In addition to decreasing LDL oxidation, data support an effect of ET on critical cells in atherogenesis (monocytes, smooth muscle cells and endothelium) that are potentially anti-atherogenic. The primary aim of the present proposal is to test the effect of AT supplementation (1200 IU/day of RRR-AT) in a placebo-controlled, randomized double blind trial over 2 years on the progression of carotid atherosclerosis in patients with coronary artery disease (stable angina pectoris or previous myocardial infarction). Subjects (n=120) recruited would have to be on the American Heart Association Phase II diet and a HMG CoA reductase inhibitor for at least one year and have an LDL cholesterol ,125 mg/dL on 2 visits at least 4 weeks part during the 10 month lead in phase. Intimal-medial thickness (IMT) of both carotids, including the common carotid, the bulb and the proximal internal carotid will be determined by high resolution B-mode sonography. At six month intervals blood samples will be obtained for liver enzymes, creatinine, complete blood count, lipid profile, antioxidant and fatty acid levels, LDL oxidation, plasma soluble CAMs (cell adhesion molecules) and monocyte activity. Also, an early morning urine sample will be obtained for F2-isoprostanes, a direct measure of lipid peroxidation. IMT will be determined at baseline, 1, 1.5 and 2 years. The mean change in IMT and rate of progression will be compared between the AT and placebo groups. Following isolation, the LDL will be subjected to copper catalyzed oxidation over a 5hour period. From this will be obtained the lag phase and oxidation rate. Isolated monocytes will be activated with lipopolysaccharide and the following activities assayed: superoxide anion release, interleukin-1beta release and adhesion to human endothelium. F2 isoprostanes and VAM, ICAM, and E-& P-selectin will be quantitated by ELISA. AT levels and the parameters of LDL oxidation and monocyte activity will be correlated with changes in IMT. If this study show that high-dose AT supplementation is beneficial in retarding atherosclerosis this could emerge as an important adjunctive therapy in the management of cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECT OF METABOLISM/ATHEROSCLEROSIS
PF4
ON
LIPOPROTEIN
Principal Investigator & Institution: Sachais, Bruce S.; Pathology and Lab Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 15-JAN-2000; Project End 31-DEC-2004 Summary: (Adapted from applicant's abstract) Atherosclerosis is the most common cause of death in the United States. Elevated plasma levels of LDL are a major risk factor for the development of this disease. The major pathway by which LDL is catabolized is via the LDL-receptor (LDL-R). Therefore, factors that impede LDL-LDL-R interactions promote atherosclerosis. An unexplored question is whether platelet activation modulates LDL-R function. Whereas the role of platelets in the terminal thrombotic phase of this disease is well- established, it is less certain whether persistent platelet activation accelerates the pathogenesis of the atherosclerotic plaque. In view of the fact that certain clusters of positively charged residues on apolipoprotein Beta-100 are required for optimal binding of LDL to the LDL-R, the investigators tested the hypothesis that platelet factor 4 (PF4], an abundant lysine rich protein released upon
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platelet activation, can complete for receptor binding and thereby impede lipoprotein clearance and catabolism. Pilot data provided support for this hypothesis by demonstrating that PF4 binds to the LDL-R with nM affinity, inhibits the binding and degradation of LDL in vitro, and prolongs the plasma clearance of LDL in vivo. It is now proposed to study the biochemicals basis of the PF4-LDL-R interaction in greater detail and to develop models to elucidate the role of this platelet protein in the development of atherosclerosis through the following specific aims; 1) Specific Aim 1: Characterization of PF4 binding to the LDL-R and it's consequences in vitro. The binding kinetics of PF4 to cell lines that overexpress LDL-R as well as to recombinant soluble receptor will be measured using surface plasmon resonance. The effect of PF4 on the binding and cellular metabolism of LDL and apoE will be studied using cells that are genetically lacking or overexpress LDL-R and in which the level of proteoglycan expression has been controlled. Specific Aim 2: Effect of PF4 on lipoprotein metabolism and atherosclerosis in vivo. Adenoviral-mediated gene transfer of PF4 will be used to analyze changes in LDL clearance and endogenous lipoprotein levels in vivo. The propensity to develop hyperlipidemia and atherosclerosis will be examined in transgenic mice that overexpress human PF4. These studies are designed to gain insight into a novel mechanism by which persistent platelet activation may promote the development of atherothrombotic disease. An understanding of the structural basis of the PF4-LDL-R interaction may identify a potential locus for therapeutic intervention. This research proposal is part of comprehensive training program designed to prepare the applicant for a career as an independent investigator in the field of vascular biology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF ENERGY HEALERS ON ATHEROSCLEROSIS Principal Investigator & Institution: Fox, Joan E.; Director; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAY-2004 Summary: (provided by applicant): Coronary artery disease is the major cause of death and disability in the United States. The goal of our research for the past 20-years has been to investigate mechanisms involved in the development of cardiovascular disease and to identify potential sites for therapeutic intervention. Evidence that poor social support systems and emotional states play a major role in the development and progression of coronary artery disease is accumulating; interventions designed to address the emotional state of the patient have demonstrated beneficial effects. The rapidly growing field of psychoneuroimmunology is providing insights into potential mechanisms by which emotional health could affect physical health. There is growing interest in the use of interventional programs that include practices such as meditation and yoga that are based on Eastern spiritual philosophies. A basic premise of these philosophies is that we are interconnected through an unidentified life-force. Energy healers suggest that this life-force may be a component of emotionally supportive social interactions. They claim to be able to channel this life-force to clients, thus improving the emotional and spiritual health of the client. Several positive trials on energy healing, including two positive trials on cardiac patients, suggest that this CAM modality is worthy of further study. Cholesterol-fed rabbits provide a well-established model for evaluation of the effects of potential therapeutic agents on the development of atherosclerosis. A marked reduction in the development of lesions in rabbits receiving caring attention has been reported. In this application, we propose a pilot study using cholesterol-fed rabbits. The effect of energy healing treatments on lesion development will be investigated. Should these studies provide evidence for beneficial effects, the
30
Atherosclerosis
availability of an animal model would allow the design of future studies in which effects on physiological markers, sites of action, or important features of delivery of energy healing could be investigated in detail. The Specific Aims of the present application are: 1) to evaluate the possibility that energy healing treatments may decrease the progression of atherosclerosis in a rabbit model of cholesterol-induced atherosclerosis, 2) to evaluate the possibility that energy healing treatments may decrease markers of neuroendocrine and sympathetic nervous system activation in a rabbit model of cholesterol-induced atherosclerosis 3) to evaluate the possibility that energy healing treatments can minimize the activation of endothelial cell gene transcription in a rabbit model of cholesterol-induced atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENDOTHELIAL DYSFUNCTION IN ATHEROSCLEROSIS Principal Investigator & Institution: Southan, Garry J.; Inotek Pharmaceuticals Corporation 100 Cummings Ctr, Ste 419E Beverly, Ma 01915 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-OCT-2003 Summary: Nitric oxide and peroxynitrite are reactive, short-lived species that are important mediators of atherosclerosis. One of the downstream pathways of peroxynitrite-mediated vascular injury is related to activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS). Based on vitro and in vivo preliminary data, the applicants propose that the PARS pathway may play a role in the pathogenesis of the endothelial dysfunction associated with atherosclerosis, and propose studies to directly test this hypothesis. The first aim of the current project is to establish time course of PARS activation and associated vascular dysfunction in atherosclerosis, and to correlate these alterations with reactive nitrogen species formation in the vasculature. Blood vessels will be obtained form mice at various time points after initiation of atherosclerotic changes, induced by two distinct experimental models (collar and Apo/E models). Reactive nitrogen species formation and PARS activation will be investigated using immunohistochemistry, vascular reactivity will be investigated using ex vivo using isometric tension measurements in vascular chambers. The second aim of the project is to perform direct studies into the role of PARS-related endothelial dysfunction, as it relates to the atherosclerosis-associated development of endothelial dysfunction. We will utilize chronic oral treatment with PARS inhibitors of two different classes, followed by evaluation of changes in vascular reactivity and the progress of atherosclerosis. Our studies will provide novel mechanistic information on atherosclerosis-related endothelial dysfunction which will be utilized for the future design and commercial development of novel vasculoprotective agents. PROPOSED COMMERCIAL APPLICATIONS: The annual anticipated revenues for an effective agent for the therapy of atherosclerosis is over 50 billion in the US alone. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ARTERIOLES
ENDOTHELIAL
DYSFUNCTION
OF
HUMAN
CORONARY
Principal Investigator & Institution: Miller, Francis J.; Asst Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 15-APR-1997; Project End 31-MAR-2002 Summary: (Adapted from applicant's abstract) The candidate has recently completed a fellowship in Cardiovascular Disease and is currently a full-time junior faculty member in the Department of Internal Medicine at the University of Iowa. He has demonstrated
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success in basic research of coronary physiology and shows promise of attaining independent status. The proposed studies will be performed in well-funded and established laboratories under the co-sponsorship of Drs. Beverly Davidson and David Gutterman at the University of Iowa. Environmental support and facilities available to him are outstanding. The proposed studies will provide the applicant training in cellular and molecular biology which will allow him to integrate these disciplines and extend his physiologic studies. The training and experience outlined in this proposal will be invaluable in the applicant's goal to be competitive as an academic cardiologist in the field of vascular biology. There are studies of the hypotheses that 1) atherosclerosis impairs endothelium-dependent vasodilation of the human coronary microcirculation as a result of increased oxidative stress, and that 2) vascular dysfunction can be improved by endothelial cell overexpression of superoxide dismutase. The proposal is novel in its study of diseased human coronary microvessels and the use of gene transfer to correct clinically important vascular abnormalities. Isolated atrial or ventricular arterioles, obtained fresh at the time of cardio-pulmonary bypass or cardiac transplant, will be prepared for videomicroscopic examination of internal diameter. The effect of acute (pyrogallol) and chronic (atherosclerosis) oxidative stress on endothelium-dependent dilation will be tested. The mechanism of impaired vasodilation in atherosclerosis will be determined by examining the sensitivity of vascular smooth muscle to nitric oxide and non-nitric oxide stimuli, evaluate the role of vasoconstrictor prostanoids, and assess for decreased cellular levels of SOD in atherosclerosis. The candidate will also determine whether overproduction of superoxide dismutase is protective against reactive oxygen species mediated dysfunction. In-vitro adenoviral transfer of genes for three human SOD isoforms (manganese, copper-zinc, or extracellular), each with specific cellular localization, will be performed in arterioles from patients with and without atherosclerosis. Functional changes of endothelial vasodilation in these vessels will be tested. Preliminary data by the applicant support the feasibility of the proposed studies. Species differences of vascular biology and limitations in animal models of disease underscore the importance of performing these studies. (End of abstract) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENVIRONMENT, CNS, AND ATHEROSCLEROSIS IN AN ANIMAL MODEL Principal Investigator & Institution: Mccabe, Philip M.; University of Miami Coral Gables University Sta Coral Gables, Fl 33124 Timing: Fiscal Year 2001; Project Start 01-JUL-1986; Project End 31-JUL-2006 Summary: (provided by applicant): We have demonstrated that social behavioral factors can influence the progression of atherosclerosis in an animal model genetically predisposed to the development of disease, the Watanabe Heritable Hyperlipidemic Rabbit (WHHL). It was found that stable social conditions, accompanied by increased affiliative social behavior, slowed the progression of atherosclerotic lesions in these animals. In contrast, animals in unstable social conditions, displaying increased agonistic behavior, and animals housed singly exhibited significant aortic pathology. These data could not be explained entirely by resting plasma glucocorticoids, gonadal steroids, lipid levels, nor resting cardiovascular measures. It is hypothesized that chronic activation of the sympathetic nervous system (SNS) accelerates the progression of atherosclerosis. In addition, we will examine Central Nervous System (CNS) mechanisms underlying the regulation of the SNS and hypothalamic pituitary adrenocortical axis (HPA), focusing primarily on the roles of central corticotropinreleasing hormone (CRH) and oxytocin (OT) in the control of SNS and HPA responses.
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Atherosclerosis
It is hypothesized that CRH, released centrally during stressful behavior, stimulates the SNS and HPA, thereby accelerating the progression of disease. In contrast, central OT, which has been linked to increased affiliative behavior, may buffer the organism during stable social conditions from the effects of stress by inhibiting the HPA axis and SNS activity. Animals housed singly exhibited low glucocorticoid levels and showed little stressful behavior, yet still developed significant atherosclerosis. These sedentary animals gained more body weight than the other groups and developed profound hyperinsulinemia, suggesting that risk factors related to the Insulin Metabolic Syndrome may be particularly important for the progression of disease in this group. The proposed work will: 1) assess the role of the SNS in behaviorally-related atherosclerosis via selective adrenergic receptor antagonists, 2) determine the role of central CRH in the regulation of SNS activity and atherosclerosis during chronic social stress via a centrally administered CRH antagonist, 3) measure changes in the release of OT in the hypothalamic paraventricular nucleus as a function of social environment through the use of chronic microdialysis, 4) determine the role of central OT in the regulation of HPA and SNS activity, and its relationship to atherosclerosis via a centrally administered OT antagonist, 5) assess the impact of dietary restriction or daily exercise on risk factors related to the insulin metabolic syndrome and atherosclerosis and in individually-caged WHHLs, and 6) examine the influence of social environment on atherosclerosis in the heterozygous WHHL, an alternative model that more closely parallels lipid status and disease progression in a large percentage of humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF CAROTID ARTERY ATHEROSCLEROSIS IN YOUTH Principal Investigator & Institution: Davis, Patricia H.; Neurology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-MAR-2004 Summary: (Adapted from Investigator's Abstract) The atherosclerotic process begins in childhood and progresses through adult life resulting in coronary heart disease (CHD), stroke, and peripheral vascular disease. There is a need to identify young people at risk for premature atherosclerosis so that preventive measures can be instituted before occlusive vascular disease occurs. The ultrasonic measurement of carotid intimal-medial thickness (IMT) allows detection of early atherosclerosis and is related to incident CHD and stroke in older adults. In 1970, a population of school age children and adolescents was first examined in Muscatine, Iowa. A sample of 776 members of this longitudinal cohort, who are representative of the initial childhood population, is now aged 37 to 45 years. Their risk factors were measured in childhood, young adulthood and twice in later adult life, and they have undergone measurement of carotid IMT as well as electron beam computed tomography to identify coronary artery calcification (CAC). In this cohort, carotid IMT is significantly associated with CAC as well as current LDL cholesterol and systolic blood pressure, but only 14 percent of carotid IMT variability can be explained by these risk factors. Parents of the cohort have been assessed for cardiovascular morbidity and mortality. In this application the investigators propose to do the following: (1) examine the third generation to determine whether the offspring of cohort members with premature atherosclerosis and/or a familial history of cardiovascular disease have increased carotid IMT or elevated risk factors; (2) identify risk factors for progression of carotid IMT over four years in this cohort; and (3) measure putative risk factors for increased IMT (serologic evidence of Clamydia pneumoniae or cytomegalovirus infection, high sensitivity C-reactive protein,
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fibrinogen, plasminogen activator inhibitor-1 and glycosylated hemoglobin). The investigators state that the study has the potential of providing information which would allow identification of subjects at risk for atherosclerosis at an early age and may lead the way to interventions to halt or slow progression of atherosclerosis prior to the development of clinical disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF CAROTID IMT PROGRESSION IN MESA Principal Investigator & Institution: Polak, Joseph F.; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): This application seeks to determine the factors associated with progression of sub-clinical atherosclerosis and to evaluate the associations between the progression of sub-clinical atherosclerosis and the development of clinically manifest atherosclerosis. Changes in sub-clinical atherosclerotic disease are measured noninvasively using high resolution B-mode ultrasound and presented as changes in wall thickness (in millimeters) of the carotid artery (carotid IMT). Carotid IMT is well recognized as a measure of atherosclerotic burden. Progression of disease is hypothesized to precede the development of clinical events. The current application is also designed to be able to compare progression of carotid IMT with changes in coronary calcium score, a measure of coronary artery disease. Development of clinical atherosclerosis is evaluated by onset of clinical events (myocardial infarction, stroke, angina.) in an established cohort with a broad agedistribution and a multi-ethnic composition (MESA: Multi-Ethnic Study of Atherosclerosis). As compared to previous published works on the topic, this application offers the opportunity of measuring atherosclerosis across a broad age distribution and in a multi-ethnic cohort using state-of-the-art technologies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPIDEMIOLOGY: ATHEROSCLEROSIS
OXIDATIVE
STRESS
AND
EARLY
Principal Investigator & Institution: Jacobs, David R.; Professor; Epidemiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from Investigator's Abstract) The risk of coronary heart disease (CHD) can be diminished significantly by the modification of dietary intakes and the cessation of smoking. A reduction of saturated fat intake and an increase in plant foods has both been associated with beneficial effects on serum cholesterol, hypertension, atherosclerosis and mortality. These dietary and lifestyle modifications are hypothesized to act by increasing antioxidant protection and reducing oxidative damage. Such damage is a primary mechanism in the development of atherosclerosis, as demonstrated by numerous basic science studies and suggested by several small human feeding trials. Specific oxidatively modified macromolecules have been found in advanced atherosclerotic lesions. However, no information is available on the early time course of oxidative damage in human subjects. The investigators propose to measure oxidation products from several classes of compounds, thereby studying multiple pathways in atherogenesis, and serum antioxidants. They will study a cohort of about 3500 black and white young men and women. Between June, 2000 and June, 2001 (15 years after baseline), CARDIA participants will be assessed for subclinical CHD by the
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Atherosclerosis
measurement of coronary calcification at the earliest stages of detectability. In addition, endothelial dysfunction will be assessed by measurement of plasma adhesion molecules and microalbuminuria. By measuring several kinds of antioxidants and assessing oxidative damage in classes of compounds, this project will test the association of oxidative damage and early/subclinical CHD. In addition, utilizing the extensive biochemical and sociodemographic data collected over the first 15 years of CARDIA, they will define the confounding effects of traditional CHD risk factors. The investigators state that the analyses will allow testing several major hypotheses about the early evolution atherosclerosis and CHD. They further state that the conclusions will identify new strategies for the prevention of CHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN, INFLAMMATION AND ATHEROSCLEROSIS Principal Investigator & Institution: Herrington, David M.; Professor; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2001; Project Start 21-SEP-2000; Project End 31-JUL-2003 Summary: (Adapted from the Investigator's Abstract) Recently, the Heart and Estrogen/progestin Replacement Study (HERS) found no effect of 4.1 years of estrogen plus progestin therapy in women with established coronary disease. Recent data showing elevated levels of C-reactive protein (CRP) in women taking hormone replacement (HRT) suggest that this null effect in HERS could be due to a previously unrecognized pro-inflammatory effect of HRT offsetting the other benefits of estrogen. However, there are several important questions remain concerning HRT, CRP, and atherosclerosis. First, do the estrogen-associated changes in CRP reflect a true increase in systemic vascular inflammation mediated through interleukin-6 (IL-6) and other inflammatory cytokines, or are they simply due to a direct effect of estrogen on hepatic synthesis of CRP? Second, are baseline measures of CRP and other inflammatory markers, or estrogen-associated change in these markers related to subsequent progression of angiographically defined coronary atherosclerosis? To answer these questions, the investigators propose to measure CRP and other inflammatory markers in stored serum from participants in the Estrogen Replacement and Atherosclerosis (ERA) trial, an NHLBI-sponsored angiographic trial to examine the effects of daily conjugated estrogen (0.625 mg) or estrogen plus medroxyprogesterone acetate (MPA) (2.5 mg) on progression of coronary disease in postmenopausal women. By examining the relationships between these measures, treatment assignment, and progression of coronary atherosclerosis, they hope to clarify the effects of estrogen use on vascular inflammation and the consequences of these effects for the pathogenesis of atherosclerosis. The investigators state that this information may help guide clinical decision-making and future research initiatives because of the fundamental role that estrogen therapy and vascular inflammation play in modulating risk for heart disease in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FETAL DETERMINANTS OF ATHEROSCLEROSIS Principal Investigator & Institution: Palinski, Wulf; Professor of Medicine; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): We previously showed that atherogenesis already begins during fetal development and that maternal hypercholesterolemia during
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pregnancy is associated with enhanced fatty streak formation in fetuses and a much faster progression of atherosclerosis in normocholesterolemic children that could not be explained by conventional risk factors. Although in humans inherited genetic differences are likely to contribute, we hypothesize that maternal hypercholesterolemia per se induces pathogenic events in fetal arteries that determine their later susceptibility to atherosclerosis. We also hypothesize that oxidative stress caused by maternal hypercholesterolemia leads to persistent changes in the expression of genes modulating atherogenesis. An important corollary is that cholesterol lowering and antioxidant interventions in mothers during pregnancy may provide long-lasting benefits to their offspring. Using genetically homogeneous animal models, we recently provided direct evidence for the causal role of maternal hypercholesterolemia and oxidative stress in both enhanced fetal lesion formation and accelerated post-natal atherogenesis. We also provided proof in principle for persistent regulation of gene expression in the arterial wall. We now propose to better define the in utero programming associated with maternal hypercholesterolemia, to identify genes influencing post-natal susceptibility to atherosclerosis, and to investigate whether interventions during pregnancy also decrease the susceptibility in offspring of "normocholesterolemic" mothers. Different levels of maternal hypercholesterolemia and antioxidant protection will be achieved by transferring embryos of LDL receptor deficient (LDLR-/-) mice into treated or untreated C57BL/6, LDLR -/- or apoE -/- mice. Offspring will be subjected to post-natal atherogenic conditions and lesion formation followed over time. Laser-capture microdissection, gene microarray and PCR techniques will be used to determine persistence of gene regulation and its correlation with atherosclerosis, immunocytochemical presence of gene products and measurements of oxidative stress. These studies should yield fundamentally new insights into in utero programming and atherogenic mechanisms, and may establish a novel preventive approach. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESISTANCE
GENETICS
OF
ATHEROSCLEROSIS--ROLE
OF
INSULIN
Principal Investigator & Institution: Hsueh, Willa A.; Professor of Medicine and Chief; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: The theme of this investigation is the hypothesis that insulin resistance (IR), hyperinsulinemia and a subset of components of the IR syndrome promote changes in the vasculature leading to atherosclerosis, and that there are common genes linking these factors and coronary artery disease (CAD). We have developed a multidisciplinary approach incorporating gene mapping in animals and in man with human and animal physiologic analyses that involve extensive phenotyping of traits related to IR and atherosclerosis to test this hypothesis, Because of their family structure and the high prevalence of IR, Mexican American (MA) families with CAD represent an ideal ethnic group in which to identify genes linking to both IR and CAD and to determine the critical physiologic relationships of IR and hyperinsulinemia and its associated metabolic changes to vascular structural alterations leading to atherosclerosis. Exciting preliminary data in MA families supports both our hypothesis and the overall feasibility of completing the goals outlined in this grant application. Three experienced teams of senior research investigators and three supportive cores constitute a highly focused, collaborative, integrated investigation that features expertly designed and performed phenotyping; innovative methods of mathematical genetic analysis pioneered and
36
Atherosclerosis
successfully applied by members of our team; state of the art genetic mapping technology through the newly created UCLA Human Genetics Department; and physiologic investigation of the role of hyperinsulinemia and IR in atherosclerosis through novel mechanisms leading to vascular damage including the role of paraoxonase, hepatic lipase and alterations in lipid turnover, as well as lipid oxidation. An important theme of this program project is gene->cell->tissue->animal- >human>gene translation. The combination of detailed human and animal phenotyping, comprehensive genetic mapping, novel tissue investigations and lipid turnover studies outlined herein provides a powerful, multi- dimensional approach to identify genes and pathophysiologic mechanisms linked to atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCOSAMINE, ATHEROSCLEROSIS
PROTEOGLYCAN
SYNTHESIS
AND
Principal Investigator & Institution: Tannock, Lisa R.; Medicine; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 18-JUN-2001; Project End 31-MAY-2003 Summary: (APPLICANT'S ABSTRACT): Glucosamine is a nutritional supplement commonly used for the relief of joint pain. However, it is not subject to FDA regulation and its long-term safety is unknown. Glucosamine is used in the synthesis of glycosaminoglycan chains on proteoglycans. Vascular proteoglycans play a key role in atherogenesis due to their retention of atherogenic lipoproteins in the arterial wall. Thus, glucosamine use could potentially be atherogenic. Previous studies have yielded conflicting results with respect to the atherogenic potential of glucosamine. Some studies have suggested that glucosamine may have pro=atherogenic effects, while others suggest an anti-atherogenic effect. This grant proposes to investigate the role of glucosamine in vascular. proteoglycan biosynthesis and lipoprotein retention in vitro, andin vivo. The major hypothesis of this grant is that glucosamine supplementation will result in altered proteoglycan synthesis by vascular-smooth muscle cells, which will in turn result in an altered propensity to atherosclerosis. Depending on the nature of these altered vascular proteoglycans, glucosamine supplementation could either enhance susceptibility to, or protect against, atherosclerosis. This grant proposes to study the effect of glucosamine supplementation on the structure and function of proteoglycans synthesized by monkey aortic smooth muscle cells in vitro. Studies will be performed to determine the effect on-degree of sulfation, size, and ratio of classes of proteoglycans synthesized by vascular smooth muscle cells, and the retention of atherogenic lipoproteins by these altered proteoglycans. In addition, this grant proposes to address the effect of glucosamine supplementation in vivo. LDL receptor deficient mice, a mouse model of atherosclerosis that has a human-like lipoprotein profile, will be supplemented with oral glucosamine, and the extent of atherosclerotic lesions will be determined. The findings from the proposed study should provide important insights into the potential effects of glucosamine supplementation on atherosclerotic cardiovascular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCOSE, INSULIN IN DIABETIC VASCULAR DISEASE Principal Investigator & Institution: Nadler, Jerry L.; Kenneth R. Crispell Professor of Medicin; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904
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Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-JUL-2006 Summary: This program project will investigate the role of hyperglycemia and insulin resistance in the excess cardiovascular disease due to diabetes. The program will utilize innovative and multi-disciplinary approaches to address the overall unifying theme that elevate glucose and/of insulin resistance leads to accelerated cardiovascular disease by increasing oxidative stress and inflammatory signals in the vessel wall. A hypothesis developed in the initial funding period will be expanded to evaluate the role of lipoxygenase (LO) activation in mediating the oxidative and inflammatory changes associated with atherosclerosis and vascular injury. A strength of the program will be the use of both small and large animal models to more clearly evaluate the genetic and molecular mechanisms leading to cardiovascular disease in diabetes. These models will also allow the evaluation of potentially therapeutic to prevent the accelerated atherosclerosis and injury response in people with diabetes. The program involves 4 projects and 3 cores. Project 1 will examine the hypothesis that activation of LO pathway can play a role in atherosclerosis and vascular injury by inducing the transcriptional regulation of key genes which regulate vascular smooth muscle cell migration and matrix remodeling. A unique aspect of this project will be the use of novel ribozymes and animal models to test the in vivo role of oxidative stress and 12-LO in these processes. Project 2 will test the hypothesis that glucose and the diabetic state induce LO expression in aortic endothelial cells and that arachidonic or linoleic acid derived oxidative lipids activate key signalling mechanisms and oxidative phospholipids which lead to the binding of monocytes to the vessel wall. This project will utilize novel ribozymes, mouse, and swine models in the cores. Project 3 will mechanistically evaluate the role of helix-loop-helix transcription factors such as Id3 in accelerated VSMC growth response to injury in insulin resistant and diabetic states. Studies will utilizes chemokines, and chemokine receptors determine monocyte recruitment to atherosclerotic lesions and b) the increased rate of atherosclerosis in diabetes can in part be explained by a more robust or earlier expression of these molecules. A novel aspect of this project will be the use of in isolated perfused carotid artery model and the therapeutic and mechanistic actions of a novel anti- inflammatory agent Lisofylline in appropriate mouse models. The synergy between the projects and use of the cores will greatly accelerate the pace of this research to understand the mechanisms of accelerated macrovascular disease in diabetes. The results form this program should provide new therapeutic advances to reduce the rate of cardiovascular disease in diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GORDON RESEARCH CONFERENCE ON ATHEROSCLEROSIS-200102 Principal Investigator & Institution: Tall, Alan R.; Professor; Gordon Research Conferences Box 984, 512 Liberty Ln West Kingston, Ri 02892 Timing: Fiscal Year 2001; Project Start 15-AUG-2001; Project End 31-JUL-2002 Summary: (provided by applicant): The 15th Gordon Research Conference on Atherosclerosis will be held at the Kimball Union Academy in Meriden, NH on June 2429, 2001. This international conference, which has been held every two years since 1971, will provide an overview of the most important recent developments in the pathobiology of atherosclerosis. The meeting will discuss the various stages in lesion development, proceeding from different risk factors, to lesion initiation, foam cell formation and regression, the inflammatory response of the vessel wall, complexity of lesions, rupture and thrombosis, genetics, intervention and diagnosis. The combined interaction of various risk factors in mechanisms of atherogenesis, particularly
38
Atherosclerosis
hyperlipidemia, hypertension and diabetes, will be discussed. Throughout special emphasis will be placed on cutting edge technologies and resources that are relevant to the biology of atherosclerosis. Accordingly, there will be discussion of functional genomics, expression arrays, proteomics, sequence database utilization and new approaches in human and mouse genetics. Nine sessions are planned and will cover the following topics: 1. Etiology of Atherosclerosis: Lipoproteins and other Risk Factors (hypertension, diabetes, homocystinemia); 2. Lesion Initiation; 3. Inflammation; 4. Foam Cell Formation and Regression; 5. Complexity of Lesions; 6. Plaque Rupture and Thrombosis; 7. Genomic Approaches; 8. Intervention and Diagnosis; 9. The Genome Project and Vascular Disease. The conference will be a major vehicle for the integration of new knowledge in the field of atherosclerosis research. In order to stimulate an interdisciplinary dialogue, speakers will be invited who represent distinct but overlapping areas of research such as hypertension, genomics, lipoproteins and vascular biology. The conference will encourage the participation of women and minorities. Some of the invited speakers represent young scientists at the beginning of their independent careers. Participation of young scientists will also be encouraged through poster sessions. The conference is planned in such a way that by the end of the conference, the participants will have derived an overall understanding of the biogenesis of atherosclerosis, and will have a clear picture of the latest most exciting developments in the field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GROUP V SPLA2 IN ATHEROSCLEROSIS Principal Investigator & Institution: Webb, Nancy R.; Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): A critical event in early atherogenesis is the retention of low-density lipoprotein (LDL) particles in the subendothelium through their binding to intimal proteoglycans. These retained lipoprotein particles are exposed to several modifying enzymes in the arterial wall, including lipases, oxidizing enzymes, and proteases. A multitude of biological responses to such modified LDL, including the recruitment and lipid loading of macrophages, leads to the initiation and progression of atherosclerosis. The extracellular matrix (ECM) appears to play an active role in this process by not only mediating the retention of LDL particles, but by also modulating the activity of various enzymes towards LDL. Thus, in regions where LDL is being accumulated, the co-localization of LDL, ECM, and LDL modifying enzymes leads to a self-perpetuating cascade of events that culminates in atherosclerosis. The identification and characterization of molecules and the manner in which they interact to contribute to this process, is central to our understanding the mechanisms that underlie susceptibility to lesion formation. This proposal aims to study a novel form of secretory phospholipase A2, Group V sPLA2, which we now show is present in human and mouse atherosclerotic lesions specifically associated with macrophages. We hypothesize that Group V sPLA2and LDL in the proximity of macrophages leads to the localized production of aggregated and/or fused lipoprotein particles, which consequently leads to foam cell formation. To test this hypothesis, the following specific aims are proposed: Specific Aim 1): To test the hypothesis that Group V sPLA2 produces modifications in LDL particles that lead to increased uptake by macrophages. This will be accomplished by analyzing LDL particles after hydrolysis by Group V sPLA2 to determine particle composition, density, and extent of aggregation and/or fusion; quantifying the effect of Group V sPLA2 hydrolysis on the delivery of LDL lipid to macrophages, and
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determining whether other factors in the arterial subendothelium, namely sphingomyelinase and ECM, promote Group V sPLA2-mediated effects. Specific Aim 2): To test the hypothesis that macrophage expression of Group V sPLA2 in the vessel wall results in increased atherosclerosis. This will be achieved by transplanting fetal liver hematopoetic stem cells over-expressing wild-type Group V sPLA2, or a mutant form of the enzyme that is deficient in proteglycan binding, into LDL receptor-/- mice. Measuring lesion size and cholesterol/cholesterol ester content will assess the extent of atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GSTS: OXIDATIVE STRESS IN EARLY ATHEROSCLEROSIS Principal Investigator & Institution: Boor, Paul J.; Professor; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Atherosclerosis is a major cause of morbidity and mortality. Oxidative stress has been strongly implicated in the pathogenesis of atherosclerosis, but few studies have addressed the mechanisms by which the vascular wall defends against oxidant, or electrophilic, injury. Our recent data show that a specific subtype of glutathione Stransferase (GST), GST A4-4, is selectively induced in vascular smooth muscle cells (VSMCs) of rat aorta in response to electrophilic injury caused by alpha, betaunsaturated aldehydes such as acrolein, 4-hydroxynonenal (4-HNE) and 4hydroxyhexenal (4-HHE), which are toxic end products of lipid peroxidation implicated in the pathogenesis of atherosclerosis. Our recent data in human tissue also supports a role for HGST A4-4 in the pathogenesis of atherosclerosis. Our recent data in human tissue also supports a role for HGST A4-4 in the atherosclerotic plaque. Our hypothesis is that the human vascular GST isozyme, HGST A4-4, functions in the cell's defense against highly reactive alpha, beta- unsaturated aldehydes that are toxic end products of lipid peroxidation, and are implicated in the pathogenesis of atherosclerosis. We expect hGST A4-4 is induced in vascular smooth muscle cells (VSMC) and endothelium during development of the early human atherosclerotic plaque in response to oxidative stress. By manipulating this enzyme in cultured vascular cells from rat, and in genetically altered in vivo mouse models (GST-/-; apoE-/-; a double knock of apoE and GST) we will be able to alter the course of oxidative injury and atherogenesis. Using human blood vessels , our Specific Aim #1 will determine if HGST 4-4 induction and accumulation of suspected aldehyde/aldehyde adducts are early markers of oxidative injury in the early or "fibrous" human atherosclerotic plaque. In Specific Aim #2, we will utilize already- developed rat VSMC, and endothelial cells made resistant to alpha, betaunsaturated aldehydes, to examine the role of GST during oxidative/atherosclerotic stress. In Specific Aim #3 we will use a recently developed genetically altered mouse GST during oxidative/atherosclerotic stress. In Specific Aim #3 we will use a recently developed genetically altered mouse GST knockout of GST and apoE, to manipulate GST A4-4 in order to worsen/hasten the development of atherosclerosis. These studies will focus on early events during oxidative damage and defense mechanisms in the vascular wall, so that therapeutic strategies to prevent initiation and propagation of the atherosclerotic plaque may be devised. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEMOSTATIC FACTORS IN VASCULAR DISEASE Principal Investigator & Institution: Degen, Jay L.; Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229
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Timing: Fiscal Year 2001; Project Start 01-AUG-1994; Project End 31-JUL-2002 Summary: (Investigator's abstract) The long-term goal of this research program is to use gene-targeting and gene-transfer technologies in mice to directly test the following general hypothesis: hemostatic factors are critical in the progression and pathobiology a wide spectrum of diseases, including atherosclerosis, cancer, fibrotic lung disease, sickle cell disease, and other diseases associated with acute or chronic tissue injury. The specific objective of this research plan is to directly test the hypothesis that two key hemostatic factors, fibrinogen (Fib) and plasminogen (Plg), are important in the progression of vessel wall disease. A substantial amount of indirect evidence has pointed to a critical role of hemostatic factors in the early progression of atherosclerotic disease that generally precedes and predisposes to myocardial infarction and stroke, including the presence of copious amounts of fibrin(ogen) and fibrin degradation products within early lesions, high local expression of procoagulants and fibrinolytic system components, epidemiological identification of specific hemostatic factors as risk factors for coronary artery disease, and the incorporation of mural thrombi into advanced plaques. The recent generation of gene-targeted mouse lines predisposed to atherosclerosis as a consequence of selected deficiencies in apolipoproteins or their receptors, coupled with the availability of mice with selected deficits in key hemostatic factors, has provided an opportunity to directly test the importance of specific coagulation and fibrinolytic factors in atherosclerosis in vivo. In Specific Aim 1 of this proposal, the progression of atherosclerotic disease will be quantitatively and qualitatively compared in LDLR-deficient and control C57B1/6 mice that either retain or lack Fib and Plg. Age, diet, and gender will be examined as independent variables in these studies. The mechanistic role of fibrin(ogen) in the acceleration of atherosclerosis observed in Plg-deficient mice will be determined in Specific Aim 2 by detailed analysis of atherosclerotic disease in mice with single and combined deficiencies in those hemostatic factors. In Specific Aim 3, the impact of Fib and Plg deficiencies on neointima formation following chronic inflammatory challenge will be evaluated. The proposed studies will provide a more detailed understanding of the role of specific coagulation/fibrinolytic factors in vascular disease and could ultimately lead to new and valuable therapeutic strategies for the prevention and treatment of vascular disorders causing life-threatening arterial occlusion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIV PROTEASE INHIBITORS AND ATHEROSCLEROSIS Principal Investigator & Institution: Smart, Eric J.; Professor; Physiology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant) We hypothesize that HIV protease inhibitors alter macrophage class B scavenger receptor-dependent uptake and efflux of cholesterol thereby promoting the formation of lipid-laden macrophages and atherosclerotic lesions. A major drawback to the use of HIV protease inhibitors is that they promote the development of dyslipidemia, which is an established risk factor for the development of atherosclerosis. Numerous reports have suggested a causal link between protease inhibitor therapy and atherosclerosis; however, this has not been unequivocally demonstrated in a large-scale clinical trial. The dyslipidemia, which is primarily an increase in triglycerides, is unlikely to completely account for the development of atherosclerotic lesions in HIV patients because atherosclerosis is a multifactorial disease that is not controlled by a single factor. Our preliminary data demonstrate that HIV protease inhibitors have direct effects on macrophages, which are critical cellular
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mediators in atherosclerotic lesion development. The generation of lipid-laden macrophages is a key event in atherogenesis and is thought to be due, in part, to unregulated uptake of modified lipoproteins. Such aberrant cholesterol accumulation is influenced by the functions of the class B scavenger receptors, SR-BI and CD36. Both receptors are found in atherosclerotic lesions and on macrophages. In addition, both receptors can mediate the uptake of lipoprotein cholesterol and the efflux of cellular cholesterol. Our preliminary data demonstrate that peritoneal macrophages isolated from LDL receptor null mice given the HIV protease inhibitors, amprenavir, indinavir, or ritonavir, contain more SR-BI and CD36 than aged-matched controls. In addition, all three protease inhibitors increased SR-BI and CD36 levels in THP-1 cells, our macrophage cell model system. The protease inhibitors also increased the cellular cholesterol content in both the in vivo and in vitro model systems, which is consistent with our hypothesis. Importantly, mice given amprenavir, indinavir, or ritonavir had significantly more atherosclerotic lesions than control mice. We will test two Specific Aims. Aim 1 : To determine the effects of HTV protease inhibitors on SR-BI and CD36 dependent cholesterol uptake and efflux. Aim 2: To determine the leukocyte (i.e., macrophages, etc.) specific effects of HIV protease inhibitors on atherosclerotic lesion formation in LDL receptor null mice that have been transplanted with bone marrow from SR-BI x LDLR and CD36 x LDLR null mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERTENSION / ATHEROSCLEROSIS PARADIGMS Principal Investigator & Institution: Herrera, Victoria L.; Profesor of Medicine; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2003 Summary: Clinical and experimental data demonstrate unequivocally that hypertension accelerates atherosclerosis. This is an intriguing pathogenic phenomenon since the interaction is quite unambiguous for two complex diseases marked by clinical and genetic heterogeneity. Currently, the mechanisms underlying this interaction have not been elucidated. Strategic animal models are needed to mechanistically dissect pathogenesis. We have developed a transgenic hyperlipidemia- genetic hypertensive rat model by hepatic over-expression of human cholesteryl ester transfer protein (hCETP) in Dahl salt-sensitive (S) rats. Transgene high copy number in Tg[hCETP]53 Dahl S rats elicits aortic, coronary and intramyocardial atherosclerotic lesions and decreased life spans compared with no lesions in non-transgenic Dahl S controls and minor medial changes in Tg[hCETP]25 Dahl S rats with transgene moderate copy number. In this research proposal, we will investigate whether synergistic decrease of NO activity induced by both hypertension and atherosclerosis results in enhanced activated endothelial molecular and cellular changes which are then differentially amplified. as enhanced pro-inflammatory and pro-thrombotic changes leading to progressive vascular disease. The following specific aims will be studied: 1) Determined whether the endothelium of hypertensive, markedly hyperlipidemic Tg[hCETP]53 Dahl S rats exhibit exaggerated endothelial cell activation (marked by enhanced and/or sustained upregulation of ICAM-1 and P-selectin gene expression and increased monocyte adhesion compared with control age-matched normotensive, markedly hyperlipidemic Tg[hCETP]53 Dahl salt-resistant (R) male rats, and control non-transgenic age-matched hypertensive, normolipidemic Dahl S rats. 2) Determine whether exaggerated activation results in amplified dysregulation through enhanced pro-inflammatory response (marked by increased TNF-alpha expression and increased NF-kappaB activation in endothelial cells, macrophages) and/or pro-thrombotic response (marked by tissue
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factor TF expression in endothelial cells, macrophages, intimal smooth muscle cells)-distinct from corresponding arteries in control normotensive, markedly hyperlipidemic Tg[hCETP]53 Dahl R rats as well as in control hypertensive, normo-lipidemic Dahl S rats. 3) Define the hierarchical relationship of hypertension hyperlipidemia and decreased NO activity on the acceleration of atherosclerosis by determining which manipulation, high salt diet, Western Type Diet, or NO-inhibitor L-NA treatment will cause Tg[hCETP]25 Dahl S rats to exhibit similar atherosclerotic lesion phenotype similar to Tg[hCETP]53 Dahl S rats. 4) Define the mechanistic role of endothelial NO pathway in the interaction of hypertension and atherosclerosis; sufficient versus essential but not sufficient versus modifying but not essential by early, mid-point, and late-onset L-arginine treatment of Tg[hCETP]53 Dahl S rats and determine whether the acceleration of atherosclerosis by hypertension is differentially attenuated, if not significantly resolved. This research proposal will provide key information on mechanisms that underlie the acceleration of atherosclerosis by hypertension which will identify new strategies for intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOBIOLOGY OF APOLIPOPROTEIN E Principal Investigator & Institution: Curtiss, Linda K.; Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, Ca 920371000 Timing: Fiscal Year 2001; Project Start 01-DEC-1988; Project End 31-MAR-2003 Summary: Coronary artery disease, the major manifestation of atherosclerosis, is the leading cause of death in the Western world. In spite of this striking impact, the pathogenesis of atherosclerosis is till poorly understood. Controversy exists regarding the participation of innate immunity involving macrophages. (Mphi) and natural killer (NK) cells versus antigen-specific acquired immunity involving lymphocytes. Mphi predominate in atherosclerotic lesions. NK cells, although smaller in number a present as well. Furthermore the T lymphocytes that participate in acquired immunity are frequently observed in lesions and have been demonstrated to modulate lesion progression. This proposal will address directly the participation of the innate inflammatory and acquired immune responses in vivo. To demonstrate the participation of NK cells in atherosclerosis resulting from moderate as well as profound hypercholesterolemia, we will combine the use of well characterized mouse models of atherosclerosis with inbred strains of mice that are deficient in T and B cell and / or NK cell function. Our first aim is to detail the frequency and the kinetics of NK cell and T cell localization within lesions of apolipoprotein E-deficient (apo E -/-) and low density lipoprotein receptor-deficient (LDL-R-/-) mice with both moderate and severe hypercholesterolemia. This aim will determine the degree to which NK cells and T lymphocytes influence the progression of ahteroma and reveal whether T and NK cell cytokine expression are responsible for the characteristic pathology of the disease. Because the participation of NK cells will be examined in both immune-competent as well as severely immune-deficient animals, these studies will provide valuable information on the participation of NK cells will be examined in both immunecompetent as well as severely immune-deficient animals, these studies will provide valuable information on the participation of both innate and acquired immune responses in atherosclerosis. Our second aim will identify if NK cell and T lymphocyte function within atherosclerotic lesions are influenced by locally produced Mphi apo E. WE have determined that macrophage-derived apo E plays a protective role within the lesions o LDL-r-/- mice and this aim will reveal if regulation of NK cell and/or T cell function is a mechanism by which apo E bestows this protection. The successful
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completion of these studies will provide critical data about the role of T cells and/or NK cells in arherosclerosis that will aid in the development of new treatment strategies to alter the course of atherosclerosis in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IRAS FAMILY STUDY--GENETICS OF INSULIN RESISTANCE Principal Investigator & Institution: Bergman, Richard N.; Physiology and Biophysics; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2003 Summary: Insulin resistance is an important risk factor for atherosclerosis. Insulin resistance varies widely within populations, and substantial evidence indicates that much of this variation can be attributed to genetic sources. Visceral adiposity, another important atherosclerosis risk factor, is strongly correlated with insulin resistance, and this trait also appears to be under substantial genetic control. The overall goals of the proposed research project are to: 1) identify the genetic determinants of insulin resistance and visceral adiposity; and 2) determine the extent to which insulin resistance visceral adiposity, and metabolic cardiovascular disease risk factors share common genetic influences. To address these goals, we will enroll 160 families of AfricanAmerican and Hispanic background who are participating in the Insulin Resistance Atherosclerosis Study (ERAS). Approximately 1280 additional family members will be recruited. Insulin resistance will be measured using the frequently sampled intravenous glucose tolerance test, and visceral adiposity will be measured using computed tomography. A panel of other metabolic cardiovascular disease risk factors will also be assessed. A panel of 370 microsatellite markers will be genotyped from DNA, and a genome-wide scan will be performed to detect chromosomal regions containing loci that influence phenotypic variation. We will then saturate the regions of linkage identified in these analyses with additional markers and will then perform linkage disequilibrium analyses in effort to localize further the putative loci. The organization of this study will be similar to that of IRAS, with three clinical centers, a coordinating center, a central laboratory and a genetic laboratory. This center at the University of Southern California will be responsible for performing and coordinating laboratory measurements, as well as for analysis of insulin sensitivity and other metabolic parameters. This project will contribute substantially to our understanding of the genetic determinants of insulin sensitivity, and consequently to risk of atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IRAS FAMILY STUDY--MOLECULAR GENETICS Principal Investigator & Institution: Bowden, Donald W.; Professor; Biochemistry; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: Insulin resistance is an important risk factor for atherosclerosis. Insulin resistance varies widely within populations, and substantial evidence indicates that much of this variation can be attributed to genetic sources. Visceral adiposity, another important atherosclerosis risk factor, is strongly correlated with insulin resistance, and this trait also appears to be under substantial genetic control. The overall goals of the proposed research project are to: 1) identify the genetic determinants of insulin resistance and visceral adiposity; and 2) determine the extent to which insulin resistance, visceral adiposity, and metabolic cardiovascular disease risk factors share common genetic influences. To address these goals, we will enroll 160 families of
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African-American and Hispanic background who are participating in the Insulin Resistance Atherosclerosis Study (IRAS). Approximately 1280 additional family members will be recruited. Insulin resistance will be measured using the frequently sampled intravenous glucose tolerance test, and visceral adiposity will be measured using computed tomography. A panel of other metabolic cardiovascular disease risk factors will also be assessed. A panel of 370 microsatellite markers will be genotyped from DNA, and a genome-wide scan will be performed at the Mammalian Genotyping Service to detect chromosomal regions containing loci that influence phenotypic variation. We will then saturate the regions of linkage identified in these analyses with additional markers and will then perform linkage disequilibrium analyses in effort to localize further the putative loci. The organization of this study will be similar to that of IRAS, with three clinical centers, a coordinating center, a central laboratory and a genetics laboratory. This Molecular Genetics component of the study will (1) carry out genomic DNA isolation and quality control, (2) fill significant gaps and correct errors in data from the whole genome screen, and (3) carry out detailed analysis of chromosome regions which show evidence for linkage. This project will contribute substantially to our understanding of the genetic determinants of insulin sensitivity, and consequently to risk of atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: L-ARGININE METABOLISM AND CORONARY VASCULAR FUNCTION Principal Investigator & Institution: Kuo, Lih; Professor; Medical Physiology; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2003 Summary: Atherogenesis is a complex process that appears to be initiated by alterations of endothelium. An elevated level of plasma low-density lipoproteins (LDL) is thought to be responsible for the development of atherosclerosis because the characteristics of LDL-induced endothelium dysfunction are very similar to those observed in hypercholesterolemic and atherosclerotic subjects. Indeed, exposure of normal large coronary arteries to pathological concentrations of LDL inhibits endotheliumdependent vasorelaxation within minutes. However, it is unclear whether coronary microvessels (<150 MU m) are also susceptible to LDL. This issue is important because these microvessels not only contribute over 70% of coronary resistance but also play a major role in the regulation of coronary blood flow. Interestingly, many studies have shown that administration of a high dose of L-arginine normalizes atherosclerosis- and LDL-induced vascular dysfunction. Since L-arginine is a biological precursor for nitric oxide (NO) synthesis, these results may suggest that the observed vascular dysfunction is due to the impairment of NO synthesis and/or release during LDL exposure. However, the underlying mechanism responsible for this impairment has not been identified, especially at the microcirculatory level. In addition, the mechanism of restoring vascular function by L-arginine is also unclear. Therefore, it is hypothesized in this proposal that the elevated LDL, especially oxidized LDL, alters L- arginine transport and/or L-arginine/NO metabolism in the endothelium and thus leads to vascular dysfunction due to the impairment of NO synthesis and/or release. To test this hypothesis, the experiments are designed: I) to demonstrate conclusively that the deficiency in endothelial release of NO during LDL exposure is responsible for the vascular dysfunction, 2) to determine the alterations of L-arginine transport and metabolism toward the synthesis of NO during LDL exposure, and 3) to delineate the mechanism(s) of restoring vascular function by the administration of L-arginine. To
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achieve these goals, we will use both isolated arterioles (<150 MU m) and cultured endothelial cells from the porcine coronary microcirculation as experimental models. The isolated arterioles will be cannulated and pressurized for functional study. The cultured cells will be used to probe the mechanism of alteration of L-arginine/NO metabolism. The intact vessel and cultured cell studies will complement each other to address the relationship between vascular function and endothelial L-arginine/NO metabolism during exposure to atherogenic agents. Results from these studies will provide valuable information toward our understanding of the mechanism of vascular dysfunction during the development of atherosclerosis. In addition, elucidation of antiatherogenic effect of L- arginine may provide a foundation for future therapeutic manipulation of vascular function during hypercholesterolemia and/or atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIPID AND LIPOPROTEIN METABOLISM IN ATHEROSCLEROSIS Principal Investigator & Institution: Fogelman, Alan M.; Professor of Medicine & Chief; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-JUL-1983; Project End 31-JUL-2008 Summary: (provided by applicant): The major focus of this Program Project relates to the role of lipids and lipoproteins in initiating and regulating processes central to atherosclerosis, vascular calcification, and osteoporosis. During the current grant period we identified oxidized phospholipids which differentially regulate inflammatory responses and demonstrated the molecular mechanisms by which they increase monocyte binding to endothelial cells (EC). The IL-8 promoter element responsive to these oxidized lipids was different from those which respond to cytokines and LPS. An oral apoA-I mimetic peptide (D-4F) dramatically reduced atherosclerosis in LDL receptor null and apoE null mice independent of plasma or HDL-cholesterol levels. D-4F also prevented the increased macrophage traffic into arteries of LDL receptor null mice after a Western diet and influenza A infection. Matrix GLA protein was shown to regulate BMP-2 activity and an atherogenic diet induced osteoporosis in atherosclerosis suceptible but not atherosclerosis resistant mice. When a paraoxonase-1 (PON1) null mouse was constructed and bred on to an apoE null background atherosclerosis increased. Conversely, a transgenic mouse overexpressing PON1 was protected from atherosclerosis. A myeloperoxidase null mouse was constructed and surprisingly had increased atherosclerosis. The nuclear receptor LXR was shown to activate an internal promoter that produced a novel alternative form of human ABCG1. Macrophage cholesterol efflux was found to be controlled by LXRalpha. The farnesoid X-activated receptor (FXR) was shown to induce apoC-II. MRP2 was shown to be controlled by the nuclear receptors PXR, FXR, and CAR. The atherosclerosis susceptibility and resistance, respectively, of C57BL/6 and C3H/HeJ mice was shown to be due to differences in the response of their EC to mildly oxidized LDL and was independent of plasma lipids or macrophages. Using QTL analysis a segment on chromosome 6 of CAST/Ei mice was identified as being responsible for the dramatic resistance of these hyperlipidemic mice to atherosclerosis and 5-Lipoxygenase was identified as the responsible gene. Based on these findings we propose 7 Projects and 4 Cores for the next grant period. The proposed experiments will use biochemistry, cell biology, molecular biology, mouse genetics and genetically engineered mice to determine the molecular mechanisms by which lipids and lipoproteins cause atherosclerosis, vascular calcification and osteoporosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MACROPHAGE LIPID EFFLUX AND ATHEROSCLEROSIS Principal Investigator & Institution: Smith, Jonathan D.; Director, Stress Institute; Lab/Biomed Genetic/Metabolism; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2002 Summary: provided by applicant): Macrophage lipid efflux and atherosclerosis. The long-term objectives of this project are to gain insight into the mechanism of cholesterol and phospholipid efflux from macrophages to lipid-free apolipoproteins, and the role that this pathway has in preventing atherosclerosis. This project is relevant to atherosclerosis, the most common cause of heart disease, which is the leading cause of death in this country. Reverse cholesterol transport is an antiatherogenic pathway for the removal of cholesterol from the periphery to the liver, where it can be metabolized. HDL and lipid-free apolipoproteins Al and B (apoAl, apoE) are capable of acting as cholesterol acceptors from peripheral cells, and there is overwhelming evidence for a unique mechanism for efflux to apolipoproteins. This efflux pathway is associated with apoAl and apoE binding, uptake, and resecretion, and is defective in subjects with Tangier disease, due to defects in the ABC 1 gene. Macrophages are the earliest cells to accumulate lipid in the developing atherosclerotic lesion, and have been shown to be a crucial cell type in atherogenesis. The first aim of this project is to use ABC1 transfected cell lines along with morphological and genetic methods to characterize the role of endocytosis and resecretion in this lipid efflux pathway, to determine the cellular location of apoAl lipidation, and to analyze the function of various ABC1 domains by performing site directed mutagenesis and functional studies of the altered ABC1 proteins. The second aim of this project is to determine the specific role of macrophage ABC 1 in atherosclerosis. This will be determined by the use of mouse models, where ABC 1 will be overexpressed or underexpressed in macrophages in the context of LDL receptor deficiency. These studies will add to our knowledge about the mechanism of reverse cholesterol transport and its antiatherogenic role, and may lead to novel therapeutic strategies to prevent atherosclerosis in humans Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MACROPHAGE MIGRATION IN ATHEROSCLEROSIS Principal Investigator & Institution: Boisvert, William A.; Assistant Member; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, Ca 920371000 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Macrophage entry into the artery wall is an essential component of atherosclerosis whose complex nature is poorly understood. This grant addresses several different mechanisms by which macrophage entry into the vessel wall may be mediated. First, we have discovered recently that a deficiency of a leukocyte surface glycoprotein called CD43 results in reduced atherosclerosis in LDLR-/- mice. Preliminary data indicated that the reduction in atherosclerosis in the CD43-/- mice may be due to impaired macrophage migration to the lesion, although this is impossible to ascertain given the advanced nature of the lesions. Thus, aim 1 will test the hypothesis that CD43 mediates entry of macrophages to lesion sites. Migration of CD43+/+ or CD43-/- cells into lesions at various developmental stages will be examined. Direct measurement of short-term cell migration will be made using cultured macrophages. In addition, in vitro cell adhesion/migration will be used to identify any ligands that might mediate macrophage movement by binding to the CD43. Aim 2 will focus on another model of mice in which selectin-mediated leukocyte adhesion is greatly impaired. These mice lack an enzyme called fucosyltransferase VII (Fuc-TVII)
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that is essential for synthesis of ligands for all 3 (E, L and P) selectins. Fuc-TVII-/- mice will be crossed with the atherosclerosis-prone LDLR-/- mice to determine if macrophages utilize the selectin-ligand interaction to enter the atherosclerotic intima. We will also determine which of the selectin interactions is important for atherogenesis. The third aim revolves around a protein tyrosine kinase called Fes that is expressed primarily in myeloid cells and is important for myeloid development. Mice deficient in Fes display a striking defect in the ability of their macrophages to adhere. Due to its implications in atherogenesis, Fes deficiency will be studied in relation to lesion development. LDLR-/- mice will be made deficient in Fes to determine if the adherence defect in the Fes deficient macrophages will affect atherosclerotic development. In addition short term in vivo migration study with macrophages from Fes deficient mice will reveal if Fes deficient macrophages may be defective in migrating to atherosclerotic sites. These studies will provide much needed information about macrophage homing to the lesions. Moreover, if these molecules are shown to be essential for macrophage entry into the lesion, specific therapeutic targets can be devised to combat atherosclerosis by inhibiting macrophage migration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENTORED DEVELOPMENT AW
PATIENT-ORIENTED
RESEARCH
CAREER
Principal Investigator & Institution: Reilly, Muredach P.; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: PROPOSAL (Adapted from the applicant's abstract): Atherosclerosis remains the leading cause of death in the developed world. The signaling pathways involved in this chronic inflammatory disorder of the vasculature are poorly understood. PKC isozymes are potentially critical intracellular mediators of atherosclerotic regulatory signals in vivo. Recent data are consistent with a specific role for PKC in angiogenic signaling in vitro and in the development of vascular complications of diabetes in vivo. One of the challenges in the PKC field is to dissect the distinct roles of individual isozymes of PKC in atherosclerosis. It is the long-term goal of the applicant to determine the isozyme specific functions of PKC in atherosclerosis in vivo with a view to developing novel pharmacological therapies aimed at retarding this process in humans. Presently, it is unknown which PKC isozymes are activated in atherosclerotic tissue in vivo. Thus, despite the recent development of specific PKC inhibitors for use in humans, the isozymes that represent the best potential targets in atherosclerosis have not been identified. The investigator's specific aims, therefore, are: 1) to identify isozyme specific PKC activation in atherosclerotic mouse models and to modulate their activity in these models; 2) to confirm isozyme specific activation in human atherosclerosis and to investigate the effects on endothelial function of inhibition of specific isozymes inpatients with hypercholesterolemia; and 3) to examine the relevance of specific isozymes to angiogenesis in vitro and in vivo. By working closely with a multidisciplinary group with a strong background in both basic and translational research the applicant strives to obtain the practical experience necessary to develop an independent career in clinical investigation. Focussed coursework in patient-oriented research will compliment practical experience obtained during the development of this application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MICROFLUIDICS LAMINAR FLOW ENDOTHELIAL CELL ASSAYS Principal Investigator & Institution: Kumar, Rajan; Genome Data Systems, Inc. 127 Us Highway 206, Ste 27 Trenton, Nj 08610 Timing: Fiscal Year 2003; Project Start 11-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Coronary Heart Disease (CHD) and stroke are leading causes of death in the United States. The underlying cause of CHD and stroke is atherosclerosis, which is a chronic inflammatory condition of large arteries. A number of genetic and environmental factors are responsible for development of atherosclerosis. Atherosclerosis does not develop uniformly in arteries; hemodynamic characteristics of blood flow that promote laminar shear stress seem to prevent local atherosclerosis. The goal of this project is to develop a novel microfluidics system for performing laminar shear stress assays on vascular endothelium and developing a high-throughput system for atherosclerosis drug discovery. Parallel plate flow chamber has been the most popular method for simulating physiological flow conditions experienced by endothelial cells (ECs). Recently, a commercially produced flow chamber has been introduced that promises to reduce assay volume. However, for high throughput applications, such as screening for new therapeutics, none of the existing technologies are suitable. Genome Data Systems, Inc. (GDS) has developed an innovative and proprietary chip technology called GeneCard that can overcome the challenges of the existing systems. The characteristic feature of GeneCard technology is a modular approach to microfluidics that allows easy introduction of cells, tissues and other solid phase materials into fluidic devices, as well as their easy removal. During this project, GeneCard designs for efficient culture and laminar flow assay of ECs will be investigated. EC cultures will be established on GeneCard devices, and subjected to controlled laminar shear stress. Gene expression profiles of ECs using microarrays will be generated and genes that are regulated by laminar shear stress will be identified. Finally, the ability of known modulators of EC function to reverse gene expression changes induced by laminar shear stress will be investigated. The proposed method provides a user-friendly approach for investigating effects of laminar flow on EC cultures. Smaller number of cells required reduces cost and enables high throughput assays. At the successful completion of the proposed project, GDS will provide complete systems for drug discovery market as well as use the systems for internal R&D efforts and to provide contract screening service. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR ATHEROSCLEROSIS
AND
CELLULAR
INTERACTIONS
IN
Principal Investigator & Institution: Lusis, Aldons J.; Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: This subproject will test hypotheses generated in our Program using transgenic and gene targeting technologies in mice. During the present grant period, our work has focused on aspects of oxidation (paraoxonase 1, myeloperoxidase, heme oxygenase-1, and secretory phospholipase A2) and macrophage function (macrophage colony stimulating factor, scavenger receptor CD68 and the nuclear receptor LXR). We now propose to extend some of these studies of paraoxonase-1 (PON1), heme oxygenase (HO-1) and macrophage colony stimulating factor (M-CSF) and to examine the functions of two additional proteins that have emerged as candidates from studies in this program: paraoxonase 3 (PON3) and 5-lipoxygenase (5-LO). PON1 and PON3 are
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members of a family of esterases, and both are carried on HDL. Using gene targeting, we provided strong evidence that PON1 protects against atherosclerosis and inhibits lipid oxidation. During the past two years, we and others have obtained evidence for a strong anti-oxidant function of PON3, and we will now test this using gene targeting. HO-1 has proved to be difficult to examine because HO-1 null mice breed poorly, although during the present grant period we did obtain evidence for its protective function in vivo using induction and inhibition with pharmacologic agents. We now propose to utilize transgenic approaches to pursue more detailed investigations of its role in atherosclerosis. M-CSF has been a long-term interest, since we originally cloned it in the mid-1980s. The expression of M-CSF is critical in the development of atherosclerosis in mice, and null mice have more than a 100-fold decrease in lesion development on an LDL receptor null background. But precisely how M-CSF contributes to the disease and which are the relevant sites of expression are unknown. These questions will be addressed using cell-specific knockouts of the M-CSF gene. Finally, 5-LO was identified in the subproject by Lusis as the gene controlling susceptibility to atherosclerosis in a genetic cross between inbred strains CAST and C57BL/6. 5-LO knockout were then shown to exhibit dramatically reduced atherosclerosis. We now propose to examine mechanistic questions pertaining to the role of 5-LO in atherosclerosis, including effects on monocyte proliferation and apoptosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR REGULATION OF ARTERIAL THROMBOSIS Principal Investigator & Institution: Simari, Robert D.; Associate Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 05-SEP-2000; Project End 31-JUL-2005 Summary: Arterial thrombosis, a major complication of atherosclerosis, is the leading cause of death in the Western world. Thrombosis in vivo is usually initiated when endoluminal disruption leads to exposure of subendothelial procoagulants such as tissue factor (TF) to flowing blood, with binding of TF to factor VIIa resulting in activation of factors IX and X and subsequent fibrin deposition. Tissue factor pathway inhibitor (TFPI), a Kunitz-type serine-protease inhibitor, uniquely modifies the coagulation cascade in vivo by binding in a two-step process to TF-factor VIIa catalytic complex and factor Xa forming a quaternary inhibitory complex which dampens further coagulation. We have recently demonstrated that in spite of TFPI expression in atherosclerotic plaque, TF activity predominates. Thus our working hypothesis is that there is a relative deficiency of TFPI in atherosclerotic plaque and that the imbalance between TF and TFPI is an important source of vascular thrombogenicity and may contribute to plaque development and progression. To further define the importance of this imbalance, we propose two major goals. First, we will generate genetically modified mice that overexpress TFPI in a targeted manner limited to the vessel wall to determine whether altering the local balance favoring TF inhibition will inhibit arterial thrombosis and the development and progression of atherosclerosis. Second, to alter this balance in blood- derived cells, we will generate mice incapable of producing TFPI from circulating blood cells and test these mice in an established model of thrombosis. Our Specific Aims are: 1) To generate transgenic mice which overexpress TFPI in a targeted manner, 2) To determine the role of vascular TFPI overexpression in the development of atherosclerosis, 3) To determine the role of vascular TFPI expression in a murine model of arterial thrombosis and 4) To determine the role of blood-derived TFPI expression in a murine model of arterial thrombosis. We anticipate that these studies will; 1) elucidate
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new mechanisms by which the balance between TF and TFPI regulates the development of atherosclerosis and thrombosis and 2) provide insights into the relative importance of blood-derived and circulating forms of TFPI. Ultimately these insights will lead to new therapeutic approaches to prevent and treat atherosclerosis and its most important complication, thrombosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NF-KB ATHEROGENESIS
ACTIVATION
AND
ORAL
INFLAMMATION
IN
Principal Investigator & Institution: Nichols, Timothy C.; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Atherosclerosis, the major cause of death and disability in the United States, is a chronic disease with inflammatory components. Our overall objective is to use molecular, cellular and animal models to study how activation of NF-kappaB contributes to atherosclerosis. This nuclear transcription factor controls the expression of many genes linked to atherogenesis, including those involved with inflammation. We hypothesize that one unifying mechanisms in this complex disease is the activation of NF-kappaB. The mechanism(s) that activates NF-kappaB in atherogenesis is unknown and the effect of inhibiting NF-kappaB atherogenesis is untested in animal models. In Aim 1, we focus on shear stress and oxidized LDL-induced activation of NF-kappaB in cultured porcine endothelium and smooth muscle cells as models for determining the mechanism(s) of activation of NF-kappaB in atherogenesis. The role of phosphorylation and degradation of IkapaB and the operative kinases and signal transduction pathways will be identified. In Aim 2, we will develop and test a series of reagents that inhibit NFkappaB activation in response to shear stress and oxidized LDL. The most promising inhibitors will be tested in Aim 3 where we will use our pigs with shear and dietinduced atherosclerosis to determine the effect of inhibiting activation of NF-kappaB. Periodontal disease has now been established as a risk factor for atherosclerosis and its thrombotic complications. It is unknown if periodontal disease contributes to the initiation or progression of atherosclerosis. NF-kappaB likely plays an essential role in bone loss due to periodontitis since IL-1beta and TNFalpha are key mediators in humans and animal models of the disease and strong activators of NF-kappaB. We hypothesize that the chronic and intense inflammatory response accompanying periodontal disease produces an excess burden of circulating mediators of inflammation that initiate or exacerbate the inflammatory components of atherosclerosis. To test this hypothesis, we will adapt a model of ligature-induced periodontitis to our pig models of atherogenesis. Our goal in Aim 4 will be to determine if the presence of periodontal inflammation contributes to the initiation and/or progression of atherosclerosis. If so, then we will determine whether or not activated NF-kappaB is present in cells in the atherosclerotic lesion that is modulated by oral inflammation. Our data on the mechanisms involved in the critical role of NF-kappaB in atherosclerosis could lead to important therapeutic applications especially as it relates to the impact of periodontitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NITRIC OXIDE SYNTHASE ISOFORMS IN ATHEROSCLEROSIS Principal Investigator & Institution: Huang, Paul L.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-JAN-1998; Project End 31-DEC-2006
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Summary: (provided by applicant): In the previous funding period, we used eNOS and iNOS knockout mice to demonstrate that physiologic production of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS) suppresses atherosclerosis, whereas pathologic production of NO by inducible NOS (iNOS) contributes to atherosclerosis. We found that eNOS knockout mice demonstrate an exaggerated response of neointimal proliferation in response to vessel injury. Furthermore, when fed a Western type diet, eNOS/apoE dko mice develop more severe atherosclerosis than do apoE knockout mice, as well as complications of aortic aneurysms, aortic dissection, distal coronary artery disease, myocardial infarction, and ventricular dysfunction. In contrast, iNOS/apoE dko mice develop less atherosclerosis, and show evidence for decreased levels of lipid oxidation. We propose now to extend these results by examining the molecular and cellular mechanisms by which abnormalities in eNOS expression contribute to atherosclerosis. Specifically, we hypothesize that abnormalities in eNOS phosphorylation at serine 1179 and threonine 497 underlie the molecular mechanisms of endothelial dysfunction, and that statins and estrogens exert their beneficial effects by correcting these abnormalities. We are generating transgenic and knockin mice that carry mutations at these phosphorylation sites, to mimic both the phosphorylated form (aspartate substitution) and an unphosphorylatable form (alanine substitution). These mice will be useful tools to determine the extent to which abnormalities in phosphorylation lead to increased vessel injury response, and propensity to diet induced atherosclerosis in the apoE knockout mouse model. A second hypothesis is that expression of NOS isoforms by circulating cells, in addition to vascular endothelium and smooth muscle, affects atherosclerosis. We propose to use bone marrow transplantation studies to assess the importance of NOS isoform expression by bone marrow-derived cells to vessel injury and atherosclerosis in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORAL INFECTIONS, CAROTID ATHEROSCLEROSIS AND STROKE Principal Investigator & Institution: Desvarieux, Moise; Assistant Epidemiology; Columbia University Health Sciences New York, Ny 10032
Professor;
Timing: Fiscal Year 2001; Project Start 15-JUN-2000; Project End 31-MAY-2005 Summary: The overall aim of the proposal is to conduct a prospective cohort study to determine and quantify the independent contribution of periodontal infections to the risk of atherosclerosis and vascular disease in a tri-ethnic population. Seizing the opportunity of the initiation of a larger cohort of stroke incidence in a community of Northern Manhattan where Blacks, Whites and Hispanics live together, and utilize the same health care facilities, we have assembled a multidisciplinary team of investigators in the fields of dentistry, medicine, and public health. 1,050 patients will be randomly selected from the community for the first 18 months of the study and followed over a period of 3 years. At baseline, they will undergo a comprehensive periodontal examination assessing clinical, radiologic, microbiologic (species specific DNA probes), immunologic (species-specific antibodies to periodontal pathogens) and inflammatory (GCF cytokine levels and systematic C-reactive protein and fibrinogen levels) parameters in addition to their extensive investigation for vascular risk factors (lipid profile, homocysteine, glucose, EKG, echocardiography.). At baseline and at 3-year follow up, they will also undergo a high resolution B-mode Doppler ultrasound to measure carotid atherosclerosis. All subjects will be re-interviewed every year. Those who report a change in their clinical status suggestive of an outcome event in the period before the 3rd year assessment will be brought in for evaluation. The concurrent measures of local markers of infection and inflammation together with systemic markers
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of infection and inflammation should help determine which of the infection or the inflammation component of periodontal disease better explains the purported association with atherosclerosis and stroke. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OXIDATIVE DNA DAMAGE AND ATHEROSCLEROSIS Principal Investigator & Institution: Blair, Ian A.; A.N. Richards Professor of Pharmacology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Oxidative DNA Damage and Atherosclerosis: Reactive oxygen species (ROS) can damage cellular macromolecules such as DNA and proteins. DNA damage results directly from ROS, or from ROS-derived lipidhydroperoxides that break down to form the alpha,beta-unsaturated aldehyde genotoxins, 4-oxo-2-nonenal, 4 hydroxy-2-nonenal, and 4,5-epoxy-2(E)-decenal. Lipid hydroperoxides are also formed enzymatically from 15-lipoxygenase (15-LOX) and from cyclooxygenase-1 (COX-1) and COX-2. We have recently shown that 4 oxo-2-nonenal and 4-hydroxy-2- nonenal are formed by two distinct pathways during the homolytic breakdown of the linoleic acid-derived prototypic omega-6 lipid hydroperoxide, 13(S)hydroperoxyoctadecadienoic acid (HPODE). One pathway involves the intermediate formation of hydroperoxide-derived alkoxy radicals and also results in the formation of 4,5-epoxy-2(E)-decenal. The other pathway involves the intermediate formation of the potential genotoxin 4-hydroperoxy-2- nonenal, which then either undergoes a l-electron oxidation to give 4-oxo-2- nonenal or a 1-electron reduction to give 4-hydroxy-2nonenal. 4,5-Epoxy-2( E)-decenal forms unsubstituted etheno-2?-deoxyadenosine adducts with DNA and so provides an important link with lipid peroxidation and DNA damage known to occur in human tissues. In recent studies, we made the surprising observation that vitamin C can stimulate the breakdown of lipid hydroperoxides to alpha,beta-unsaturated aldehyde genotoxins. Furthermore, the remarkable efficiency of this process suggests that vitamin C could give rise to significant levels of DNA-damage in vivo. If lesions derived from direct oxidative damage or lipid-hydroperoxidemediated DNA damage are not repaired, replication can lead to mutations or apoptosis. Apoptotic cell death is involved in the pathogenesis of a variety of cardiovascular diseases, including heart failure, myocardial infarction and atherosclerosis. The ability to directly identify and quantify lipid hydroperoxide-mediated DNA damage will make it possible to assess the role of such lesions in atherosclerosis. We plan to determine the potency of each of the lipid hydroperoxide-derived bifunctional electrophiles in causing DNA-damage. Using in vitro models, the relative importance of lipid hydroperoxide mediated damage when compared with damage that occurs from ROS will be determined. The spectrum of adducts formed in 13(S)-HPODE and 9(R)-HPODE-treated cultured human endothelial cells pre-loaded with vitamin C will be characterized. DNA-adduct formation arising from endogenously generated 13(S)-HPODE and 9(R)HPODE will also be assessed. The catalytic efficiency of COX-2-mediated linoleic acid oxidation to 13(S)-HPODE and 9(R)-HPODE is much greater than COX-1. However, normal endothelial cells only express COX-1. Therefore, COX-2 will be induced and the cells will then be treated with linoleic acid. The resulting HPODEs will be subjected to vitamin C-mediated decomposition. Cellular DNA will be isolated and the major adducts will be quantified. With these studies in hand, DNA-adduct formation in endothelial cells, leukocytes and urine from a mouse model of atherosclerosis will be examined. Finally, lipid hydroperoxide-derived DNA-adducts will be quantified in leukocytes and urine from normal subjects and from patients diagnosed with
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atherosclerosis. The relative importance of lipid hydroperoxide-derived and ROSderived covalent modifications will then be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PDAY CARDIOVASCULAR SPECIMEN AND DATA LIBRARY Principal Investigator & Institution: Strong, Jack P.; Boyd Professor and Head; Pathology; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from the applicant's abstract) This project is for the maintenance of the specimen and data base emanating from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) and Risk Factors in Early Human Atherogenesis (RFEHA) studies (PDAY Archive) so that it can be used effectively by investigators for continued study of atherosclerosis during the next five years. PDAY and RFEHA were investigator-initiated multi-center cooperative studies based on a rigidly developed protocol, which had anatomically standardized samples of aorta and coronary arteries of 3,000 young black and white subjects, age 15-34, who died suddenly of trauma. Risk factor data was also obtained in a majority of the cases. So far these studies have yielded over 75 publications by the PDAY group. These reports in turn have generated a widespread enthusiastic response from investigators throughout the scientific community in the U.S. and abroad. Many of these investigators are currently utilizing or planning to utilize the PDAY Archive as a resource for their studies on atherosclerosis and coronary heart disease. This unique resource, the PDAY Archive, should continue to contribute in important ways to our understanding of atherosclerosis, the underlying cause of coronary heart disease (CHD) and most strokes. CHD and stroke are by far the leading cause of debilitating illnesses and death in this country. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PERIODONTITIS, ATHEROSCLEROSIS AND THE HOST RESPONSE Principal Investigator & Institution: Lalla, Evanthia; Division of Periodontics; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Epidemiologic studies suggest a link between periodontitis and increased risk of atherosclerosis in human subjects. Hypotheses to account for these observations include systemic inflammation primed by local periodontal infection and release of lipopolysaccharide (LPS) into the periphery, thereby activating circulating inflammatory cells, platelets and endothelial cells; direct invasion of pathogenic bacteria in the vessel wall consequent to bouts of transient bacteremia; exaggerated, "hyper" immune responses to periodontal bacteria or cross-reactivity between microbial and human antigens; or underlying predisposing mechanisms, such as genetic predilection. Most likely, interactions of these mechanisms underlie accelerated atherosclerosis in periodontal infection. Atherogenesis is a multi-stage process initiated by interaction of pathogenic lipoproteins with the vessel wall. Superimposed injury, may exaggerate the host response and accelerate atherosclerosis. To dissect the contribution of periodontal infections to accelerated vascular disease, we employed the hypercholesterolemic apolipoprotein (apo) E null mouse. Mice were subjected to oral inoculation with the periodontal pathogen Porphyromonas gingivalis, stain 381, (P. gingivalis) at age 6 weeks; at age 17 weeks, atherosclerotic lesion number and area at the aortic sinus were increased in infected vs. uninfected mice. In parallel with increased atherosclerosis, infected mice displayed serum antibody (IgG) response to P gingivalis; increased
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alveolar bone loss and elevated levels of plasma IL-6 (both correlating with extent of atherosclerotic lesion area); bacterial localization in the aorta by polymerase chain reaction; and increased tissue factor and Vascular Cell Adhesion Molecule-1 antigens, and increased antigen and activity of matrix metalloproteinase-2 in aortic extracts. Levels of plasma lipids, insulin and creatinine did not differ between infected vs. uninfected mice. Pilot studies suggest that apo E null mice infected with the fimbriaedeficient mutant of P. gingivalis 381, DPG-3, do not demonstrate increased atherosclerosis; thus, adhesion/invasion of host cells by bacteria may critically contribute to acceleration of atherogenesis by P. gingivalis. We posit that multiple mechanisms underlie accelerated atherosclerosis in periodontal disease, including systemic responses to local (periodontal) injury in inflammatory cells, platelets and the vascular endothelium, and direct invasion of bacteria into the vessel wall. We propose to employ this model to dissect the factors accelerating vascular inflammation and atherosclerosis in periodontitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PLA2, EICOSANOIDS AND VASCULAR REMODELING Principal Investigator & Institution: Rao, Gadiparthi N.; Associate Professor; Medicine; University of Tennessee Health Sci Ctr Health Science Center Memphis, Tn 38163 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Proliferative cardiovascular diseases such as atherosclerosis and restenosis are a major cause of death in the western world in general and in the United States in particular. Inflammation that follows vascular injury is believed to be important in the initiation and progression of atherosclerosis and restenosis. Several events can be triggered as c consequence of inflammation at the site of arterial injury. These are 1) lipid peroxidation, 2) arterial smooth muscle cell (SMC) growth induction, and 3) angiogenesis. All these events are characteristic of atherosclerosis and restenosis. Phospholipase A2s (PLA2s), a group of enzymes that break down membrane phospholipids generating arachidonic acid and lysophospholipids have been implicated in inflammation process. We hypothesize that PLA2 plays a critical role in the above described events leading to atherosclerosis and restenosis. To test this, we will address three specific aims: 1) determine the role and type of PLA2 in growth factor-induced arachidonic acid release and mitogenesis in SMC, 2) study the effects of various growth factors on eicosanoid production and determine the role of eicosanoids in mitogenic signaling events induced by these agonists, and 3) mechanisms. The results of this proposal will provide new information in regard to the role of PLA2 and eicosanoids in the modulation of SMC growth and angiogenesis, the important events in the pathogenesis of atherosclerosis and restenosis and provide rationale to design drugs in the prevention of progression of these vascular lesions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PON2 AND PON3 PROTEINS IN ATHEROSCLEROSIS Principal Investigator & Institution: Reddy, Srinivasa T.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): A number of pathophysiological observations in humans and animal models led to the hypothesis that atherosclerosis, a disease of the large arteries that is the primary cause of coronary heart disease (CHD) and stroke, is a multifactorial chronic inflammatory disease in which low plasma levels of HDL and
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high plasma levels of LDL, are a strong predictor of the condition. LDL oxidation is considered to be an essential process in the development of atherosclerotic lesions. The pro-inflammatory constituents of oxidized LDL are various oxidized phospholipids resulting from the scission and rearrangement of oxidized, unsaturated fatty acids. HDL and HDL-associated enzymes possess anti-atherogenic properties that are due, in part, to their inactivation of oxidized LDL. Although genetic and biochemical studies demonstrated anti-atherogenic role for paraoxanase-1 (PON1), a HDL associated protein, to date, the physiological functions of PON family of proteins; PON1, PON2 and PON3, remain unknown. Based on our preliminary findings, we hypothesize that PON2 and PON3 proteins inhibit the accumulation of oxidized phospholipids in LDL, protect artery wall cells against oxidative stress from reactive oxygen species (ROS) and oxidized phospholipids, and prevent the development of atherosclerotic lesions. In this application, we propose to i) characterize the biochemical and enzymatic properties of PON2 and PON3 proteins, ii) determine cellular localization, products of enzyme activity and the expression levels of PON2 and PON3 proteins in HDL and hyperchloesterolemic animal models, iii) develop transgenic mice and knockout mice to determine the physiological function of PON2 and PON3 proteins as well as the role of PON2 and PON3 in atherosclerosis, and iv) identify and characterize proteins that interact with PON2 and PON3 to delineate the biological substrates of PON2 and PON3 proteins. Understanding the biology and function of the PON proteins will pave way for the discovery of novel therapeutic agents in the fight against atherosclerosis and other inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREMATURE ATHEROSCLEROSIS IN RHEUMATIC DISEASES Principal Investigator & Institution: Crow, Mary K.; Professor; Hospital for Special Surgery 535 E 70Th St New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): While the renal and central nervous system manifestations of systemic lupus erythematosus (SLE) often present as compelling indications for aggressive cytotoxic therapy, recent data demonstrate that a significant proportion of those patients have asymptomatic cardiovascular disease (CVD) that goes unrecognized and can eventually result in important morbidity and mortality. Our center has performed a major case-control study to document the prevalence of premature atherosclerosis among patients with SLE and is extending that study to patients with rheumatoid arthritis (RA). Although SLE patients and controls were comparable in CVD risk factors, atherosclerosis (carotid plaque) was more prevalent in SLE patients (37 vs. 15%, p<0.001). To elucidate the underlying mechanisms that account for premature atherosclerosis in these patients, a panel of proinflammatory mediators in peripheral blood was assessed. The data were unrevealing of relevant mechanisms, as SLE patients either with or without carotid plaque expressed elevated levels of cytokines, soluble adhesion molecules, and soluble CD154. However, important clues regarding potential disease mechanisms were revealed based on analysis of microarray data from a subset of the SLE study subjects. The data have stimulated the hypothesis that activation of the platelet-monocyte-endothelial cell axis contributes to premature atherosclerosis in SLE. Preliminary data suggest that specific gene products that may be important mediators of vascular damage are increased in expression in SLE patients with carotid plaque. The proposed research will investigate the expression of these vascular mediators in our cohort of SLE and RA patients characterized for carotid disease and will study the functional relationship among the cells that express these
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factors. The specific aims are: 1) to investigate the expression of CD154 in rheumatic disease patients with premature atherosclerosis; 2) to investigate the expression of potential biomarkers of vascular disease in rheumatic disease patients with premature atherosclerosis; and 3) to determine the role of platelets and monocytes in generating pro-atherogenic mediators. Early identification of biomarkers in those patients who will go on to develop premature atherosclerotic disease and institution of biomarkers in those patients who will go on to develop premature atherosclerotic disease and institution of appropriate therapy should have a major impact on patient health and survival. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROINFLAMMATORY EFFECTS OF CD44 ON ATHEROSCLEROSIS Principal Investigator & Institution: Pure', Ellen; Professor; Wistar Institute Philadelphia, Pa 191044268 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Applicant's abstract): Atherosclerosis is an inflammatory process that results in the formation of unstable coronary lesions vulnerable to disruption and subsequent thrombosis. Cell adhesion molecules (CAMs) participate in the recruitment of inflammatory cells, in cell-cell and cell-matrix interactions, and in signal transduction within the developing atherosclerotic lesion. CD44 is a widely expressed CAM that serves as a principal receptor for hyaluronan, an extracellular matrix glycosaminoglycan that accumulates in atheroslerotic lesions. CD44 is expressed in a low affinity state on most primary cells but is activated to a high affinity state in the presence of inflammatory stimuli. CD44 has been implicated in a variety of chronic inflammatory responses. We investigated the role of CD44 in the development of atherosclerosis in apoE-deficient mice. CD44-deficiency had no effect on plasma cholesterol levels but the extent of atherosclerosis in apoE-/-.C0444-/- mice was markedly reduced compared to apoE4-.CD44+I. littermates. The goal of the proposed studies is to determine the molecular and cellular mechanisms by which CD44 promotes atherogenesis. The following are the specific aims: 1. Define the role of CD44 in promoting atherosclerosis. The role of CD44 at different stages of development of atherosclerotic lesions will be determined in apoE-/-.CD44-/- mice of different ages and by treatment with anti-CD44 antibodies. The impact of CD44 deficiency on atherosclerosis in LDLRI- mice will be determined. We will assess functional activation of CD44 and determine the molecular form of CD44 involved in promoting atherogenesis. 2. Determine the relative effects of CD44 expression on bone marrow-derived hematopoietic cells versus vascular cells on atherogenesis and define the role of soluble CD44 in atherogenesis. We will determine if CD44 on hematopoietic cells alone or on non-hematopoietic cells alone in bone marrow chimeras promotes atherogenesis. Transgenic mice expressing CD44 on endothelial cells and vascular smooth muscle cells on the background of CD44 deficiency will be created and atherosclerosis analyzed. The contribution of soluble CD44 to atherogenesis will be determined. 3. Determine the cellular and molecular mechanisms by which CD44/HA interactions promote atherogenesis. We will test the hypotheses that: a)CD44/HA interactions promote leukocyte homing to sites of atherosclerotic lesions; b) CD44 and HA mediate macrophage-smooth muscle cell interactions; c) CD44 acts to organize hyaluronan-rich pericellular matrix; and d) CD44 deficiency impacts on the vascular gene expression profile using microarray technology. Since CD44 plays an important role in inflammation but is not required for normal leukocyte circulation, it is particularly attractive as a potential target for novel therapeutic interventions in atherosclerosis.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: QUANTITATIVE ANAYLSIS OF AGING RETINA Principal Investigator & Institution: Curcio, Christine A.; Professor; Ophthalmology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 15-JUL-1990; Project End 31-JUL-2003 Summary: Improved treatments for age-related maculopathy (ARM), the leading cause of untreatable vision loss among the elderly in the developed world, lie in better understanding of early ARM. On the basis of our preliminary data, we hypothesize that early age-related maculopathy is an ocular form of atherosclerosis. According to this hypothesis, the pathophysiology of ARM involves two mechanisms similar to those that occur during aging and atherosclerosis in the inner wall of the large arteries: According to this hypothesis, the inner wall of the large arteries: an age-related deposition of serum-lipoprotein-derived esterified cholesterol and unesterified cholesterol (EC and UC) in association with extracellular matrix proteins; and a disease-related deposition of a UC-rich material with the participation of local cells. Using a unique resource for human donor eyes and a well-established animal model for experimental atherosclerosis, we propose three aims to test several predictions of this hypothesis. 1) In human eyes, we will determine how the EC and UC content of Bruch's membrane varies with age and retinal location, using filipin fluorescence and digital microscopy. We will identify EC-rich particles in Bruch's membrane by determining how solvents affect filipin fluorescence and ultra-structure. We will characterize the lipid composition of isolated Bruch's membrane using an enzymatic assay and gas-chromatography-mass spectrometry. 2) In human eyes, we will determine the morphology of membranous debris occurs in peripheral retina. We will determine the UC content of membranous debris and photoreceptor outer segments using filipin fluorescence, digital microscopy, and ultrastructural stereology. 3) In rabbit eyes, we will determine if an extended diet of cholesterol supplementation results in deposition of EC in Bruch's membrane EC, using autoradiography to localized systemically injected radiolabeled tyramine-cellubiose-low density lipoprotein in tissue sections. Results from these aims will be valuable in assessing the extent to which ARM and atherosclerosis share pathogenetic mechanisms with regard to the accumulation and source of extracellular cholesterol. This information is required in order to determine if effective treatments for atherosclerosis should be considered for the treatment of early ARM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RAGE AND MECHANISMS OF VASCULAR AND MONOCYTE DYSFUNCTION Principal Investigator & Institution: Stern, David M.; Dean and Chief; Physiology/Cellualr Biophysics; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: Sustained endothelial and mononuclear phagocyte dysfunction is critical to the pathogenesis of chronic vascular disorders. Non-enzymatic glycoxidation of proteins and lipids forming Advanced Glycation Endproducts (AGEs) in the vasculature and tissues is accelerated in atherosclerosis, diabetes and renal failure. Interaction of AGES with Receptor for AGE (RAGE) on endothelium and monocytes perturbs cellular properties critical to vascular and tissue homeostatic processes, and causes chronic cellular activation. The central hypothesis of the Program Project is that AGE-RAGE-
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mediated modulation of endothelial and monocyte functions compromises physiologic effector mechanisms and eventuates in aggressive atherosclerosis, delayed wound repair, and impaired resolution of local inflammation. Employing glucose intolerance as the stimulus for enhanced AGE formation, our pilot studies have shown that antagonism of AGE-RAGE interaction suppresses accelerated atherosclerosis, ameliorates wound healing and diminishes inflammatory consequences of soft tissue infection. Project 1 will exploit our recently developed murine model of accelerated atherosclerosis associated with glucose intolerance to probe the role of RAGE in rapid formation of vascular lesions. Project 2 will extend our concept to a secondary intention wound model in insulin- resistant mice in which AGE-RAGE-mediated cellular dysfunction underlies compromised tissues reparative mechanisms. Project 3 will focus on local inflammation/infection in AGE-rich soft tissues using a model of gingivitis triggered by bacterial infection. The overlapping host response mechanisms triggered by atherogenesis, wound repair and local inflammation, the intimate involvement of endothelium and monocytes, as well as the central role of AGE binding to RAGE, provide the basis for close interactions among the three Projects. By collaborative studies between each of the Projects, the contribution of RAGE will be determined using transgenic mice and mutated RAGE molecules. At the end of this Program Project, we expect to have generated new and important information related to vascular and monocyte dysfunction underlying accelerated atherosclerosis, impaired wound healing and the compromised host response to local inflammation common to disorders characterize by tissue deposition of AGEs. These data should provide insight into a novel target for the development of future therapeutic agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF PLATELET-DEPENDENT THROMBOSIS Principal Investigator & Institution: Fay, William P.; Associate Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: Enhanced tissue factor (TF) expression within atherosclerotic lesions is considered a critical determinant of arterial thrombosis. However, tissue factor expression is not restricted to the blood vessel wall, and recent studies suggest that circulating leukocytes contain a pool of TF that can be mobilized rapidly to support platelet-dependent arterial thrombosis. The overall goals of this application are to define the roles of circulating tissue factor in acute arterial thrombosis and normal hemostasis, and to elucidate how leukocyte expression of tissue factor contributes to atherosclerosis progression and plaque thrombogenicity. We have developed a murine model of carotid artery injury that generates platelet-rich thrombi in a tissue factor dependent manner. We have shown that this model can identify molecular determinants of thrombosis and thrombolysis in injured arteries, and we have utilized hematopoietic stem cell transplant strategies to restrict gene expression in mice. We have documented that active TF is present in mouse peripheral blood, and that TF antigen is present in murine atherosclerotic lesions. In the proposed experiments we will test the following hypotheses: 1) circulating TF is an important determinant of platelet thrombosis and normal hemostasis after vascular injury, 2) leukocyte-derived TF plays a key role in atherosclerosis development in mice, and 3) thrombosis in atherosclerotic arteries depends not only on vascular wall TF, but also on blood-associated TF, the levels of which are responsive to circulating lipid concentrations. In collaboration Drs. Owen and Simari Mayo Clinic, we will test these hypotheses in a series of in vivo experiments that
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apply our thrombosis models to mice whose tissue factor expression is restricted by gene targeting and hematopoietic stem cell transplant strategies. The proposed experiments will test in vivo a hypothesis that challenges a central paradigm in arterial thrombosis-that thrombogenic TF originates solely from the vascular wall. We anticipate that our studies will: 1) elucidate new mechanisms by which leukocytes and tissue factor regulate platelet-dependent thrombosis, and 2) provide important insights into the role of leukocyte TF in atherosclerosis development and plaque thrombogenicity. These experiments have important implications for fur understanding, treatment, and prevention of arterial thrombosis and atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF ANGIOTENSIN II IN ATHEROSCLEROSIS Principal Investigator & Institution: Kon, Valentina; Associate Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-APR-1992; Project End 31-MAR-2007 Summary: Description (provided by applicant) Angiotensin II (Ang II) has a critical role in tissue destruction in a variety of chronic conditions. Ang II antagonism has become a dominant therapeutic intervention in a number of cardiovascular, renal and hypertensive disorders that has unexpectedly revealed benefit in atherosclerosis. Atherosclerosis is characterized by some of the same processes that destroy other tissues, however, its pathophysiology is unique in its absolute dependence on lipid deposition within the vessel wall. Thus, although the acute sequelae of atherosclerosis occur later in life, the lipid deposition begins in utero and vascular remodeling proceeds throughout childhood. This underscores that further understanding of atherogenesis can lead to preventive measures that can begin in childhood. The PI's preliminary data suggest that non-hypertensive dose of Ang II promotes initiation of atherosclerotic lesion without affecting the lipid profile. Clinical and animal studies suggest that Ang II affects local vascular accumulation of lipids, although the precise mechanisms are not understood. Monocyte infiltration and uptake of lipid constitute the hallmark of atherosclerosis, namely, formation of macrophage foam cells. Macrophages have recently been revealed to have a crucial role in atherosclerosis. Thus, macrophages can provide sufficient lipid acceptors to correct hyperlipidemia and prevent atherosclerosis, conversely, even without affecting the plasma lipid profile, perturbations in macrophage lipid metabolisms, especially lipid efflux, promotes atherosclerosis. How Ang II relates to macrophage function is not well known. The PI's preliminary data indicate that Ang II regulates macrophage accumulation following injury; that macrophages are a source of Ang II; that Ang II promotes development of atherosclerotic lesions; that macrophages in the atherosclerotic lesion express AT1 receptor; and that macrophages deficient in AT1 receptor have more lipid efflux. These observations form the basis for these projects, which is to define the role of Ang II within the vessel walls and within macrophages in atherosclerosis. We will use chimeric mice with transplantation of genetically engineered hematopoetic stem cells into genetically engineered mice. The effects of bone marrow-or vessel-deficiency in Ang II on atherosclerosis will be assessed in vivo. In addition, in vitro macrophage studies will examine the role of Ang II in atherogenic processes including macrophage lipid handling, migration and apoptosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE ATHEROGENESIS
OF
CHLAMYDIA
PNEUMONIAE
INFECTION
IN
Principal Investigator & Institution: Kuo, Cho-Chou; Professor; Pathobiology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2004 Summary: (Adapted from the Applicant's Abstract): Chlamydia pneumoniae (TWAR) is a common human respiratory pathogen. In recent years, there has been mounting evidence showing that this organism might play a role in atherosclerosis. Because coronary heart disease is a leading cause of death in this country, the overall goal is to investigate the immunopathogenic mechanisms by which C. pneumoniae infection contributes to the development of vascular disease. The proposed studies will exploit our recent findings from mouse model studies linking C. pneumoniae infection and atherosclerosis and in vitro cell culture studies on C. pneumoniae infection of arterial wall cells. The mouse models that will be used are C57BU6 and strains derived from this background strain including, apoE-deficient and TNF-A receptor and apoE double knockout mice. Atherosclerosis in C57BU6 mice can be induced by feeding with a high fat/high cholesterol diet, while apoE mice develop atherosclerosis spontaneously on a regular diet. The specific aims are to 1) further evaluate the synergistic effect of C. pneumoniae infection and hyperlipidemia on atherogenesis by infecting mice with C. pneumoniae followed by feeding animals with a high fat/high cholesterol diet and measuring the atherosclerotic lesion development using computer assisted morphometry; 2) study the effects of C. pneumoniae infection on key components in the inflammatory process of atherosclerosis that promote atherosclerotic lesion development by recruiting lymphocytes/macrophages and eliciting inflammatory responses at lesion sites. In vitro, in vivo, and ex vivo systems will be used to assay the expression of leukocyte adhesion molecules and adherence of macrophages to the endothelial surface. The effect of TNF-A on lesion development will be investigated by infecting TNF-A receptor and apoE double knockout mice and measuring lesion development using computer assisted morphometry; 3) assess the role of macrophages in the establishment of persistent C. pneumoniae infection of atheromatous lesions using cell culture to analyze vascular cell interactions and the effect on infectivity, growth and persistence of C. pneumoniae, and characterize the growth of C. pneumoniae in macrophages loaded with low density lipoproteins (foam cells). The proposed studies should prove invaluable for understanding the disease process and developing better measures for eradication or prevention of C. pneumoniae infection and for reducing atherosclerosis and coronary heart disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF INTERFERON GAMMA AND LYMPHOCYTES IN ATHEROSCLEROSIS Principal Investigator & Institution: Schindler, Christian W.; Assistant Professor of Medicine and Micr; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2002 Summary: The evolution of atherosclerotic lesions involves an interaction between four major cell types, endothelial cells (Ecs), smooth muscle cells (SMCs), macrophages (Mphis) and lymphocytes. The contribution of ECs, Mphis and SMCs to lesion development has been characterized extensively, but the role of T-cells is poorly understood. Although these T-cells secrete Interferon (IFN)-gamma, the effect of this potent immunostimulatory cytokine remains controversial. Studies from our laboratory,
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using a murine model of diet induced atherosclerosis and IFN-gamma receptor (IFNgammaR) defectiv mice, have determined that IFN-gamma is a potent proatherogenic cytokine. These observations also implicate lesional T-cells, a source of this cytokine, in atherogenesis and suggest that a cell mediated immune response may contribute to the pathogeneis of atheroscleotic lesions. In this proposal we plan to examine the potential role of a cell mediated immune response in atherogenesis byh manipulating both the source and targets of IFN-gamma. Specifically, we plan to define the role of IFN-gamma in atherogenesis by examining atherosclerosis prone mice with defective IFN-gamma receptors in greater detail. This will entail establishing mice which are tissue specifically defective in IFN-gamma receptor function in each of the potential target tissues of IFN-gamma during atherogenesis (e.g., macrophages, T-cells, endothelial cells, smooth muscle cells, and hepatocytes). In a complementary set of experiments, to define the role of lymphocytes in atherogenesis, we plan to establish atherosclerosis prone mice which are defective in defined lymphocyte populations (e.g. B-cells, T-cells, CD4 plus and CD8 plus cells). Then we propose to correlate our studies on the role of the immune system in murine atherosclerosis to human disease by examining human lesions iwht a new set of diagnostic T-cell lymphocyte markers we have developed. The proposed aims are closely tied to the major focus of this SCOR, the employment of murine models to study important pathophysiological events in atherogenesis. Moreover, our studies will involve collaborations with each of the other projects and make extensive use of the Molecular Biology and Pathology Cores. For example, we will examine the role of IFN-gamma and lymphocytes in diabetic atherosclerosis (Project 4), and in HDL metabolism (Projects 2 and 3), and LPL action (Projects 2 and 3). These studies are likely to provide novel insight into the role of IFNgamma and the immune system in human and murine atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE ATHEROGENESIS
OF
RBCS
IN
ENVIRONMENTAL
TOXIN-INDUCED
Principal Investigator & Institution: Mukherjee, Shyamali; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: Atherosclerosis is one of the common diseases associated with exposure to environmental and industrial pollutants. Until fairly recently, pro-inflammatory interactions of oxidized low density lipoproteins (Ox-LDL) with macrophages, endothelial and smooth muscle cells were thought to be major contributors to atherogenesis. However, there is growing evidence that extravasated erythrocytes along with iron and fibrin are also present in the atherosclerotic plaques, but the exact role of RBCs on atherosclerotic plaque formation is not known, demonstrating a significant gap in our knowledge. Furthermore, several studies have clearly shown that structure and function of RBCs are altered in atherosclerosis induced by environmental pollutants. Our long-term goal is to identify a process for preventive and therapeutic intervention of environmentally related cardiovascular diseases. The objective of this proposal is to elucidate how RBCs directly or indirectly play a major role in modifying LDL and its interaction with endothelial cells, which are the initial and crucial events in developing atherosclerosis. The central hypothesis is that modification of erythrocytes by environmental factors plays a significant role in the interaction between oxidized LDL and endothelial cells thereby leading to atherosclerosis. The rationale that underlies the proposed research is that, once we understand the role of RBCs in toxicant-induced atherosclerosis, this project may lead to new strategies that can be used to prevent and
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/ or treat environmental / occupational related diseases. We will test our hypothesis by achieving the following two specific aims: (I) To determine the role of chemically modified RBCs in the oxidation of LDL and endothelial dysfunction leading to atherosclerosis (in vitro study). We will study this specific aim by pursuing two objectives. (la) Relationship between modified RBCs and Oxidized LDL: We will determine whether or not RBCs directly or indirectly modulate the oxidation of LDL Furthermore, we will determine if there are any structural and/or functional modifications within RBCs, following exposure to CS2. These experiments will provide information about whether there is a common link between modification of RBCs and oxidation of LDL, and whether or not this link is involved in the peroxide scavengers status of RBCs. (Ib) Role of chemically modified RBCs on endothelial dysfunction: We will determine whether RBCs directly or indirectly cause endothelial dysfunction by modulating (i) cell structure, (ii) the oxygen defense system, (iii) endothelial nitric oxide release and (iv) beta-adrenergic receptor coupling mechanisms. The results from these studies will provide a comprehensive understanding of the critical role of RBCs in the development of atherosclerosis. (II)To validate the in vitro result, an in vivo mouse model will be used to study whether modification of RBCs by an environmental toxicant (CS2) causes oxidation of LDL and endothelial cells dysfunction. We will determine the in vivo effect of CS2 on RBCs, LDL and endothelial cells by a single intratracheal injection into mice. This will not only validate the results found in vitro but also determine whether it is applicable to atherogenesis. Our expectation is that the results from this study will provide us with comprehensive understanding of the critical role of RBC's in environmental induced atherosclerosis. Furthermore, it will demonstrate the interaction between RBCs, LDL and endothelial cells. This study will be highly significant by increasing our knowledge of the mechanism(s) involved in atherogenesis induced by environmental pollutants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SCOR IN MOLECULAR MEDICINE AND ATHEROSCLEROSIS Principal Investigator & Institution: Cantley, Lewis C.; Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 23-APR-1997; Project End 31-MAR-2002 Summary: The experiments proposed in this SCOR in Molecular Medicine and Atherosclerosis share common themes and focus in a highly interactive program to investigate signaling involved in normal growth and differentiation of vascular tissue as well as abnormal growth that leads to atherosclerosis. A two pronged approach to atherosclerosis is proposed: 1) By understanding the growth factors, receptors and signaling proteins involved in normal vascular development and abnormal angiogenesis it may be possible to stimulate capillary growth in damaged tissues. A clinical project to investigate this possibility in human heart is proposed. 2) An understanding of the factors and signaling proteins involved in regulation of growth, migration and adhesion may also provide novel drug targets to block atherosclerosis and restenosis. Six related projects are proposed: 1) The Role of TIE-1 and TIE-2 in Pathological Blood Vessels; 2) Genetic Disorders of Vascular Development and Signaling; 3) Regulatory Elements in the PDGF-A Chain Gene and their use in directing Cell-Type Specific Gain and Loss of Function Mutations into the Vascular System of Mice. 4) The Role of PTP1 mu and SHPTP2 in Endothelial Cells, 5) Pathways of Integrin Activation and Actin Polymerization in Vascular Cells and 6) Stimulation of Human Coronary Angiogenesis with Basic FGF. These projects are enhanced by a Transgenic and Tissue-Specific Expression Core, a Protein Expression Core and an Administrative Core. Experiments
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will use the tools of cellular and molecular biology, protein chemistry, pathology, and clinical medicine. The program will be synergistically facilitated by exchange of reagents and technology, by extensive internal and external review, and by common core programs. It is anticipated that this program will advance research in this area by an emphasis on common themes and interactions, sharing the results of research efforts both within the SCOR and elsewhere and training of new scientists with interests in related basic and clinical areas within the rich environment of Harvard Medical School. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SCOR IN MOLECULAR MEDICINE AND ATHEROSCLEROSIS Principal Investigator & Institution: Witztum, Joseph L.; Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 23-APR-1997; Project End 31-MAR-2002 Summary: Atherosclerosis remains the major cause of morbidity and mortality in the Western world. Although lifestyle changes and hypolipidemic therapy decrease clinical events and even morality in high risk groups, there remains substantial diversity in the clinical expression of atherosclerosis for any given plasma cholesterol level. Among the many factors that go 'beyond cholesterol', much evidence supports the 'oxidation hypothesis' in the causation of atherosclerosis. This hypothesis states that the oxidative modification of LDL is a quantitatively important event in the atherogenic process. An important corollary is that measures that inhibit oxidation will decrease atherosclerosis. While the original interest in this hypothesis derived from observations that oxidation of LDL (OxLDL) is a prerequisite for macrophage uptake and foam cell formation, it is now apparent that OxLDL and its products can adversely effect the artery wall in many ways that are proinflammatory and proatherogenic. Investigators from around the world have propelled the oxidation hypothesis to the forefront of atherosclerosis research. The goal of the La Jolla SCOR program is to continue to intensively investigate the role of oxidation of LDL (and other lipoproteins) in the atherogenic process. We will investigate the molecular and cellular mechanisms involved in oxidation of LDL in vivo with particular emphasis on the role that macrophage-specific genes play. We will characterize the mechanisms responsible for macrophage-specific expression of the SRA gene and utilize this information to achieve macrophage- specific overexpression in transgenic mice of genes that could affect the atherogenic process, such as 15lipoxygenase. We will also develop the capacity to achieve macrophage-specific gene knockouts by use of Cre-recombinase technology. We will define the physiologic and pathophysiologic role of macrophage receptors for OxLDL with particular emphasis on CD 36 and the recently identified OxLDL-binding protein, macrosialin. We will define the importance of these receptors in vivo by generating mice that have these receptors deleted. We will determine the scope and/or limitations of antioxidant intervention in animal models of atherosclerosis and specifically test the hypothesis that for any given set of pro-oxidant stimuli, there is a threshold of antioxidant protection needed. We will investigate the role of the immune response to OxLDL with emphasis on the role of the humoral immune system and its effect on atherogenesis. We will determine the epidemiologic relationship of autoantibody titers to epitopes of OxLDL in clinical populations with respect to clinical and morphological measures of atherosclerosis and the ability of these titers to predict progression of disease. We will determine if immune complexes with LDL are found in plasma of human and animal models of atherosclerosis and if epitopes of OxLDL are found in circulating LDL. Finally, we will determine the impact of diabetes on the susceptibility of lipoproteins to oxidation. In summary, the La Jolla SCOR program proposes a multidisciplinary approach to
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determine the role that oxidative modification of lipoproteins could play in the atherogenic process. These insights may lead to improved and novel approaches to the prevention of atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TETRAHYDROBIOPTERIN: REGULATOR OF ENDOTHELIAL FUNCTION Principal Investigator & Institution: Katusic, Zvonimir S.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2001; Project Start 01-DEC-1994; Project End 31-MAR-2005 Summary: (Verbatim from the application): Cardiovascular diseases, including atherosclerosis, remain a leading cause of death and disability in the United States. Nitric oxide is a key regulator of vascular tone, platelet aggregation, white blood cell adhesion, and smooth muscle cell proliferation. Nitric oxide has also been recognized as a critical mediator of angiogenesis. Endothelial dysfunction due to decreased production of nitric oxide is an early event believed to play a major role in initiation and progression of atherosclerosis. Tetrahydrobiopterin (BH4) is an essential cofactor needed for enzymatic activity of nitric oxide synthase. BH4 plays a key role in the control of endothelial nitric oxide production. The general hypothesis of this proposal is that during development of atherosclerosis, up-regulation of BH4 biosynthesis is an adaptive response designed to preserve biosynthesis of nitric oxide and protect the vascular wall from oxidative stress. To test this hypothesis we propose studies with the following specific aims: (1) determine the effects of oxidative stress on vascular BH4 metabolism, (2) characterize the relationship between BH4 metabolism and endothelial dysfunction in arteries exposed to hypercholesterolemia in vivo, and (3) analyze the role of superoxide anion in BH4 metabolism and endothelial dysfunction in murine models of atherosclerosis. Apolipoprotein E (ApoE)-deficient mice and low-density lipoprotein (LDL) receptor-deficient mice develop spontaneous hypercholesterolemia and atherosclerosis with many features that are characteristic of lesions in humans. Preliminary findings indicate that endothelial dysfunction, as reflected in impaired endothelium-dependent relaxations, is present in murine models of atherosclerosis. The exact mechanism responsible for endothelial dysfunction induced by hypercholesterolemia is not understood. Initial analysis performed on isolated aorta of ApoE-deficient mice indicated that increased production of superoxide anions in the vascular wall plays a major role in inactivation of endothelial nitric oxide. However, the effects of superoxide anions and oxidative stress on BH4 metabolism have not been studied. To characterize the role of superoxide anion in BH4 metabolism and endothelial dysfunction, arteries from superoxide dismutase (SOD) transgenic mice and SODdeficient mice will be studied. Overexpression of SOD in ApoE-deficient mice will be used to protect BH4 from superoxide anion-induced oxidative stress and rescue endothelial dysfunction. Double knockout ApoE-SOD-deficient mice will be created to determine whether increased production of superoxide anion accelerates oxidation of BH4 and impairment of endothelium-dependent relaxation. It is anticipated that the results of the proposed experiments will provide novel and important information concerning the effect of oxidative stress on vascular BH4 metabolism and the pathogenesis of atherosclerosis. This information may help to develop new therapeutic interventions designed to prevent endothelial dysfunction and progression of atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ATHEROPROTECTIVE EFFECTS OF SR-BI Principal Investigator & Institution: Krieger, Monty; Biology; Massachusetts Institute of Technology Cambridge, Ma 02139 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (Adapted from Investigator's Abstract): The HDL receptor, scavenger receptor, class B type I (SR-BI), mediates cellular delivery of HDL cholesterol by selective lipid uptake, a mechanism fundamentally different from that of classic receptor-mediated endocytosis (e.g., LDL receptor (LDLR) pathway). SR-BI is a multiligand receptor that can bind LDL and VLDL as well as HDL, and can mediate both cellular uptake of non-lipoprotein cholesterol and cellular cholesterol efflux. It may also be involved in intestinal cholesterol absorption. In vivo studies with mice, including hepatic overexpression of SR-BI and analysis of SR-BI homozygous null mutants (SR-BI KO), have shown that SR-BI plays a key role 1) in determining the levels of plasma HDL and biliary cholesterol and HDL structure, 2) in mediating the regulated delivery of HDL-cholesterol to steroidogenic tissues and the liver, and 3) in protecting against atherosclerosis in some cases. It is also required for normal oocyte development and female fertility. The mechanisms underlying SR-BI's antiatherogenic effects are unknown; however, potential causes of the dramatically accelerated atherosclerosis see in the SR-BI/apoE double Kos relative to the single Kos include: I) changes in relative amounts of cholesterol in proatherogenic and antiatherogenic (e.g., normal HDL lipoproteins, ii) altered flux of cholesterol into or out of the vessel wall, perhaps directly due to abnormal HDL structure or reduced SR-BI-mediated efflux from macrophages, and iii) decreases in overall reverse cholesterol transport, primarily due to loss of SR-BI activity in the liver. The primary goals of this proposal are to test several of these hypotheses and further explore the role of SR-BI in cholesterol metabolism. The work will focus on tissue or cell type-specific expressing or ablation of SR-BI activity in atherosclerosis models (apoE and LDLR KO mice). We will use sense and antisense adenovirus vectors, gene-targeted knockout (KO) mice, and bone marrow transplantation to control the cell and tissue-specific expression or ablation of SR-BI activity, with a special focus on macrophages and the liver. In vitro analyses of atherosclerosis-related functions of normal and SR-BI KO macrophages and or normal and abnormal lipoproteins will be performed. IN addition, we will examine the suggestions that SR-BI may play a role in intestinal cholesterol absorption. The proposed work will help elucidate key molecular and cellular mechanisms underlying lipid lipoprotein and metabolism and atherosclerosis, and may significantly influence the direction of pharmaceutical research and development aimed toward developing new methods for the prevention and treatment of atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ROLE OF HEPATIC LIPASE IN CHOLESTEROL HOMEOSTATIS Principal Investigator & Institution: Dichek, Helen L.; Pediatrics; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: The enzyme hepatic lipase (HL) is central to cholesterol homeostasis. HL participates in the regulation of plasma cholesterol levels, a major risk factor for atherosclerosis. It also mediates steroid hormone production, by controlling access to exogenous cholesterol in steroid-producing tissues. In turn, increased production of the adrenal steroid cortisol (corticosterone in mice) as occurs in stress, depression and certain tumors of adrenal and pituitary origin, modulates the development of
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atherosclerosis: increased cortisol levels are linked to an increased risk for atherosclerosis. However, HL's precise role in atherosclerosis is unknown. HL exerts its role via at least two functions. Its catalytic function processes lipoproteins for both receptor-mediated endocytosis and selective cholesterol uptake. Its bridging function facilitates interactions between lipoproteins, receptors, and the plasma membrane, thereby modulating lipoprotein cholesterol flux. This proposal seeks to establish the respective contributions of the catalytic and bridging functions to the cellular uptake of lipoprotein cholesterol and atherosclerosis by generating transgenic mice that express wildtype HL and functional mutants of HL. These mice will be bred with mice deficient in endogenous HL(hl-/-) and with h1-/- mice that are also deficient in the low density lipoprotein (LDL) receptor to generate Ldlr-/-hl-/- mice. (The Ldlr-/- mice serves as a model for diet-induced atherosclerosis). Thus, we will determine the effect of the expression of wildtype and mutant HLs on plasma lipid and lipoprotein concentrations, composition and size, and lipoprotein turnover. The mechanisms of lipoprotein cholesterol uptake will be examined in primary hepatocyte cultures from the livers of these mice by determining the effects of wildtype and mutant HL on cellular binding and uptake of labeled lipoproteins in the presence of specific inhibitors of cellular receptors. The effect of expression of wildtype and mutant HL on atherosclerosis development will be established in high-fat diet fed wildtype and mutant HL expressing mice on the Ldlr-/-hl-/-background. In addition this proposal seeks to establish the role of HL in regulating the adrenal steroidogenic response to stress and to identify the contribution of the catalytic function of HL to the adrenal steroidogenic response to stress. This will be accomplished by determining plasma corticosterone response, adrenal cholesterol content and adrenal expression of receptors and enzymes involved in cholesterol metabolism, in response to chronic pharmacologic stimulation of corticosterone production in wildtype- and mutant HL-expressing mice and compared to nontransgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF PLASMA SPHINGOMYELIN IN ATHEROSCLEROSIS Principal Investigator & Institution: Jiang, Xian-Cheng; Anatomy and Cell Biology; Suny Downstate Medical Center 450 Clarkson Ave New York, Ny 11203 Timing: Fiscal Year 2001; Project Start 03-FEB-2001; Project End 31-JAN-2005 Summary: Sphingomyelin (SM) is one of the most abundant phospholipids in mammalian plasma. In a recent coronary heart disease (CHD) case- control study, we found that plasma SM levels and SM/(SM+PC) ratios in cases (n=279) were significantly higher than those of controls (n=277). Plasma SM levels and SM/(SM+PC) ratios were discovered to have independent predictive values for CHD after adjusting for age, plasma lipids, smoking, diabetes, hypertension, fibrinogen, and C-reactive protein. Serine palmitoyl-CoA transferase (SPT) catalyzes the initial reaction of sphingolipid synthesis, i.e., the condensation of palmitoyl- CoA with serine to yield the long-chain base (LCB) 3-ketosphinganine. The activity of SPT appears to influence SM levels in several tissues including liver, lung, and aorta, as well as plasma. We found that hepatic SPT activity in apolipoprotein E-deficient mice (apoE KO), a mouse model of atherosclerosis, was increased two fold over that in wild type (Wt) mice, in part explaining the increase of SM levels in very low density lipoprotein (VLDL) and LDL. After mammalian sphingomyelinase (SMase) treatment, the VLDL and LDL isolated from plasma of apoE KO mice had a tendency to aggregate, a process that is thought to stimulate arterial foam cell formation. Recently, two subunits of SPT, LCB1 and LCB2, have been cloned. Heterozygous LCB2 KO mice showed a reduction of plasma SM
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levels, indicating that LCB2 is directly involved in SM metabolism. Our working hypothesis is that SM- rich lipoproteins are involved in the atherogenic process by deposition and retention in artery walls as a result of local interaction with SMase. It is notable that SM has a unique biosynthetic pathway with completely different regulation from cholesterol biosynthesis. The goal of this project is to investigate the roles of SPT and SM in lipoprotein metabolism and the atherosclerosis. The major experimental emphasis will be on the use of transgenic and gene knock-out mice. The specific aims are: 1) to investigate the roles of SM in the process of atherosclerosis by crossing heterozygous LCB2 KO mice with apoE KO mice, using a specific SPT inhibitor in apoE KO ones; and using an SM- rich diet in LDL receptor KO mice; 2) to establish liverspecific LCB1 and LCB2 transgenic mice for investigating the roles of liver LCB 1 and LCB2 gene overexpression in maintaining plasma SM levels and atherosclerosis; and 3) to generate liver-specific LCB2 KO mice for investigating the role of SPT in SM metabolism and atherosclerosis. This project will provide new information on the regulation of SM metabolism and on the relationship between SM and SPT, as well as between SM and atherosclerosis. If the enrichment of SM in plasma has pro-atherogenic activity, as anticipated, then the inhibition of SPT, the key enzyme for SM biosynthesis, could be an important treatment for atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE YUCATAN MICROPIG CARDIOVASCULAR MODEL OF MENOPAUSE Principal Investigator & Institution: Goodrich, James A.; Comparative Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Menopause in women is an understudied normal aspect of the aging process that is associated with a loss of estrogen production and increased risk of cardiovascular disease and other health problems. Estrogen is generally considered to be cardioprotective. There are currently unprecedented numbers of women, about 50 million, in the United States reaching menopause; cardiovascular disease is the number one killer of postmenopausal women. Animal models provide a means of performing critical studies of the biological mechanisms and responses to existing and emerging therapies for this condition (i.e. soy protein/isoflavones). A nonprimate animal model of menopause is needed to provide a research tool that is: 1) readily available to many researchers; 2) low in risk for zoonotic disease; 3) domesticated; 4) a low cost rapidly renewable resource; 5) possess a similar coronary artery anatomy; and 6) atherosclerotic lesion to that of women. The ovariectomized Yucatan Micropig has the potential to fill this void, and will serve the interests of both the NIA and NHLBI. The overall objective of this application is to develop, characterize, and improve the Yucatan Micropig Model of Menopause for use in cardiovascular studies. This will be approached by Aim 1 clarifying the cardioprotective effects of soy protein in this model by measuring the extent of the reduction in coronary artery atherosclerosis, serum lipids, inflammatory risk factors (C-reactive Protein, Interleukin6) and blood pressure among soy, control, and conjugated equine estrogen treated groups. Establishing that soy protein can reduce coronary artery atherosclerosis in Micropigs, like it does in monkeys, would provide foundation data helpful to future soy isoflavone mechanistic studies in the Micropig model. Studies to determine how soy isoflavones and soy protein interact to reduce serum cholesterol and subsequently coronary artery atherosclerosis are needed. The next step is Aim 2, to examine the effects of these treatments on reproductive tissue. The investigators approach this aim
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by comparing uterine weights, and mammary and uterine immunohistology among these groups. The third step Aim 3, is to determine if and to what extent there is a natural female cardioprotection in the Yucatan Micropig. The investigators will approach this by comparing groups of male, ovariectomized female, and intact female Micropigs fed an atherogenic diet. The end points will be identical to those of the first aim. Finally, Aim 4, is to determine if and to what extent ovariectomized female Yucatan Micropigs experience vasomotor symptoms or hot flashes related to estrogen deficiency. This will be approached through continuous telemetric monitoring of skin temperature spikes before and after ovariectomy and then with and without estrogen replacement therapy. The future plans for this model are to use it to study the cardiovascular benefits/risks of new progestins, selective estrogen receptor modulators, tissue selective estrogens, and isoflavone products, as well as the mechanism by which soy protein lowers serum cholesterol and coronary artery atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VACCINE ATHEROSCLEROSIS
APPROACHES
TO
MODULATION
OF
Principal Investigator & Institution: Carson, Dennis A.; Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2004 Summary: Numerous lines of evidence indicates that the adaptive immune response is involved in the development of atherosclerosis. Significantly, several studies have shown that the vaccination of atherosclerosis prone animals with autologous oxidized low density lipoprotein (LDL) can reduce the incidence of atherosclerosis. This opens up the exciting possibility of therapeutic intervention for cardiovascular disease. The long-term aims of our research are to define pro- and anti-atherogenic immune responses and to develop specific vaccines that could be used prophylactically in high risk individuals or therapeutically in aged individuals. The current experimental systems in which atherosclerosis prone mice are immunized with mouse LDL in the presence of Complete Freunds Adjuvants are limited in their ability to provide this information. Mouse LDL is difficult to obtain in sufficiently large amounts for thorough immune dissection studies. Furthermore such findings have limited applications for human therapy in which immunization with human LDL is necessary and CFA can not be used as a adjuvant. Genetically altered mice expressing human ApoB, the main protein component of LDL are available. These have been bred onto an atherosclerosis prone strain, the LDLR-/- mouse, to generate hybrids which rapidly develop atherosclerosis and for which human ApoB is a self protein. In this proposal we wish to determine the feasibility of using huApoBxLDLR-/- mice for both immune dissection and vaccine development. We hypothesize that immunization of these mice with human MDA-LDL in the presence of CFA should reduce atherosclerosis in the same way as immunization of LDLR-/- with mouse MDA/LDL. Our first aim is to test this hypothesis. If proven correct, we plan as our second aim to determine whether immunization with human MDA-LDL in the presence of alternative adjuvants, which have the potential for human user, can also reduce atherosclerosis Our final aim is to dissect the phenotype and antigen specificity of the cellular and humoral autoimmune response to human LDL. The propose experiments will allow us to determine the feasibility of this system. By correlating the effect on atherosclerosis with the type of immune response induced, we can hypothesize which components of the immune response are responsible for mediating the anti or pro-atherogenic effects of vaccination.
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Our future studies will test these hypotheses and use this information as the basis for the logical development of future vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VASCULAR DAMAGE IN SLE Principal Investigator & Institution: Stein, Charles M.; Associate Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: (Verbatim from the application): Premature cardiovascular disease is a major cause of mortality in systemic lupus erythematosus (SLE) with the risk of myocardial infarction increased up to 50-fold. The mechanisms underlying accelerated atherosclerosis in SLE are poorly understood. Recent studies indicate that inflammation, through the effects of inflammatory cytokines, and oxidative stress, through lipid peroxidation, play important roles in the pathogenesis of atherosclerosis. We postulate that accelerated, inflammation-promoted atherosclerosis occurs in SLE through these mechanisms. Thus, we propose to test the hypotheses: 1) that structural and functional vascular damage is more frequent and more severe in patients with SLE than matched controls and 2) that this impairment of vascular integrity is associated with clinical and laboratory markers of inflammation, plasma homocysteine concentrations, and oxidative stress. Endothelium-dependent, flow-mediated dilation of the brachial artery measured by ultrasound, and coronary calcium volume measured by electron beam computed tomography (EBCT) will provide functional and structural measures of vascular integrity, respectively. The pathogenesis of atherosclerosis and inflammation have strong genetic components. We will examine the role of such genetic factors focusing initially on nitric oxide (NO), a mediator that affects both structural and functional vascular integrity, and test the hypothesis 3) that polymorphism of the endothelial nitric oxide synthase gene is associated with vascular damage in SLE. Of great interest are recent studies showing that HMG coenzyme-A reductase inhibitors (statin lipid lowering drugs) can reverse vascular damage, through both lipid lowering and lipid-independent mechanisms. We will examine the hypothesis 4) that vascular damage in SLE is reversible by treatment with a statin drug. The proposed studies will provide a basic understanding of the interrelationship between inflammation, oxidative stress, genetic polymorphism, and vascular damage, and will suggest strategies for reversing or preventing such damage in SLE and, potentially, other diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VASCULAR LIPOLYSIS: A DETERMINANT OF ATHEROSCLEROSIS Principal Investigator & Institution: Hui, David Y.; Professor and Vice Chairman for Research; Pathology and Lab Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Recent studies have clearly documented the importance of phospholipid and sphingolipid metabolites in atherosclerosis and vascular biology. While enzymes responsible for phospholipid and sphingomyelin hydrolysis in the vessel wall have been identified and were shown to contribute to atherogenesis, enzyme(s) responsible for lowering the level of their hydrolytic products, the bioactive lysophosphatidylcholine (LysoPC) and ceramide, have not been characterized to date. Results generated from this laboratory revealed the presence of the pancreatic-type carboxyl ester lipase (CEL) in human vascular wall. This protein is
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synthesized by aortic endothelial cells and monocyte-derived macrophages in a manner inducible by oxidized LDL (oxLDL). Importantly, CEL displayed avid bile saltindependent lysoPC and ceramide hydrolytic activities. Human CEL is also highly polymorphic, encoding proteins varying in the number of proline-rich repeating units at the carboxyl terminus. Based on these novel observations, this application proposes to test the following hypotheses: (1) CEL expression in the vasculature is an inflammatory response mechanism that protects early stages of atherogenesis by hydrolyzing and reducing the atherogenic properties of lysoPC and ceramide; (2) the number of prolinerich repeating units in the C-terminus of CEL is important in determining its ability to hydrolyze lysoPC and ceramide; and (3) CEL gene polymorphism is a determinant of individual susceptibility to modified-LDL mediated atherogenic events. These hypotheses viii be tested by experiments under 3 specific aims. Specific Aim 1 plans to produce vascular-specific CEL transgenic mice to evaluate the impact of vascular CEL gene expression on initiation and progression of the atherosclerotic plaque. Specific Aim 2 will use site-directed mutagenesis approach to test the hypothesis that the number of proline-rich repeating units at its C-terminus is an important determinant of lysoPC and ceramide hydrolytic activities of CEL, and thus the effectiveness of different CEL isoforms in protecting vascular cells against lysoPC- and ceramide-induced atherogenic events. Specific Aim 3 will identify the mechanism by which modified LDL induces CEL gene expression in human macrophages and endothelia cells. Experiments will be designed to test the hypothesis that CEL gene activation is mediated via signal transduction mechanisms as a consequence of oxLDL binding to scavenger receptors on the cell surface, or alternatively requires the internalization of specific lipid constituents associated with oxidized lipoproteins. Taken together, these studies will identify novel factors that contribute to determining atherosclerosis susceptibility. Genetic screening strategy may also be designed to identify subjects predispose to atherosclerosis for early intervention and reducing their risk of developing this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VENTRICULAR SIZE AND VALUE CALCIFICATION MEASURES BY CT Principal Investigator & Institution: Budoff, Matthew J.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 90502 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): This study is ancillary study proposal for the MultiEthnic Study of Atherosclerosis (MESA) Trial, a prospective investigation of the etiology and natural history of atherosclerosis and the ability of non-invasive tools to measure atherosclerotic burden and identify high, risk individuals in a large, population-based cohort. The development of computed tomography (CT) to evaluate coronary calcification (CC) now provides a tool to directly measure coronary atherosclerosis non-invasively. The information obtained by CT however provides more information than CC alone. CT has the ability to measure and quantitate aortic valve calcification (AVC), mitral annular calcification (MAC), aortic wall calcification and left ventricular size (LVS). The longitudinal nature of this study will allow epidemiologic associations to be established for a multitude of risk factors and these measures, establishing both the time sequence for each measure and consistency of the association in a variety of populations (ethnicity, gender, geographical location and age). Magnetic resonance imaging of the heart will also be obtained as part of the MESA trial, and comparisons of LV size by CT to magnetic resonance measures will also be performed. We propose to utilize scans already obtained as part of the calcium scanning
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(at baseline and 3.5 year follow-up), and make these four measures on baseline and follow-up scans obtained. The additive value of these simple measures to CC score could possibly provide clinicians with even more power to identify and stratify the high-risk cardiac patient with both findings. This study will also establish the prevalence, in a population based study, of all both AVC and MAC, using a technique highly sensitive to see these abnormalities. It has been postulated that a 'total atherosclerotic burden' could be obtained by adding CAC to thoracic aortic calcification, and this total atherosclerosis score (with or without MAC and AVC) might better predict cardiovascular events than CAC alone. Similarly, this cohort of 6500 patients with repeat scans can be assessed for factors that enhance or inhibit progression of LVS, mitral annular, aortic valve or wall calcification, lending insight into therapies that have efficacy against progression of aortic sclerosis or left ventricular enlargement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VESSEL ATHEROGENESIS
STRUCTURE
&
PRESSURE:TRANSPORT
AND
Principal Investigator & Institution: Rumschitzki, David; Chemical Engineering; City College of New York 138Th St and Convent Ave New York, Ny 10031 Timing: Fiscal Year 2002; Project Start 10-APR-2002; Project End 31-MAR-2006 Summary: Atherosclerosis is a disorder of the large arteries that begins with the accumulation of lipoproteins in the artery wall and develops into lesions. This accumulation is associated with high plasma lipoprotein concentrations, and thus lipoprotein transport into and accumulation in the artery wall has been the focus of intense study. If lipoprotein transport and accumulation in the vessel wall is the key to atherosclerosis, then a good understanding of these processes should explain why different vessels have different susceptibilities to disease and why these susceptibilities vary with conditions such as transmural pressure. In particular, the pulmonary artery (PA) and the large veins such as the inferior vena cava and the saphenous vein are exposed to much lower transmural pressures than the large arteries and are normally resistant to atherosclerosis. But, the PA becomes disease prone under pulmonary hypertension and large veins when exposed to artery pressure. We have developed an endothelial cell-level approach to the transport into and accumulation in the aortic wall, which seem to have vessel-in-dependent features. This proposal extends that approach to a more general venue for a detailed understanding of how the transmural pressure, vessel ultrastructure and endothelial cell turnover influence transport and accumulation in the low-pressure PA and the large vein (inferior vena cava). It does not treat vessel remodeling. The theory aims to model the roles of vessel structure and pressure conditions on the transport processes of lipoproteins in relation to atherosclerosis. The proposed research is designed by combining animal experimentation and theoretical modeling, each guiding the other, to understand these roles. In particular, the theory should be able to explain Tompkins' decade-old profiles of the tracer concentration-vsdepth into the vessel wall that coarser theories less in tune with the vessel's histology could not. It also tests the hypothesis that the kinetics of lipid binding to arterial extracellular intimal matrix and accumulation there is vessel independent; vessel dependence would derive solely from the vessel's peculiar transport problem that supplies free LDL to the tissue and its proteoglycan type/amount. The long-term goal is to be able to predict a vessel's lipid accumulation patterns based on its ultrastructure and conditions, e.g., transmural pressure. The hypothesis is that this will correlate with susceptibility to atherosclerosis and, if so, can contribute to an understanding of the effect of blood pressure on atherogenesis in certain vessels. The ultimate goal of the proposed research
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is to provide information needed for the prevention and treatment of atherosclerosis in humans. 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 “atherosclerosis” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for atherosclerosis in the PubMed Central database: •
A macrophage receptor for apolipoprotein B48: Cloning, expression, and atherosclerosis. by Brown ML, Ramprasad MP, Umeda PK, Tanaka A, Kobayashi Y, Watanabe T, Shimoyamada H, Kuo WL, Li R, Song R, Bradley WA, Gianturco SH.; 2000 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16572
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Angiotensin II --accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. by Bruemmer D, Collins AR, Noh G, Wang W, Territo M, Arias-Magallona S, Fishbein MC, Blaschke F, Kintscher U, Graf K, Law RE, Hsueh WA.; 2003 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=228408
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Atherosclerosis and Sterol 27-Hydroxylase: Evidence for a Role of this Enzyme in Elimination of Cholesterol from Human Macrophages. by Bjorkhem I, Andersson O, Diczfalusy U, Sevastik B, Xiu R, Duan C, Lund E.; 1994 Aug 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44652
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Atherosclerosis: The emerging role of inflammation and the CD40 --CD40 ligand system. by Phipps RP.; 2000 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34362
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Basal Release of Nitric Oxide from Aortic Rings is Greater in Female Rabbits than in Male Rabbits: Implications for Atherosclerosis. by Hayashi T, Fukuto JM, Ignarro LJ, Chaudhuri G.; 1992 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50529
3 4
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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Can an Antibiotic (Macrolide) Prevent Chlamydia pneumoniae-Induced Atherosclerosis in a Rabbit Model? by Fong IW, Chiu B, Viira E, Jang D, Fong MW, Peeling R, Mahony JB.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95794
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Chlamydia pneumoniae and Atherosclerosis: Critical Assessment of Diagnostic Methods and Relevance to Treatment Studies. by Boman J, Hammerschlag MR.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=118057
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Chlamydia pneumoniae and Hyperlipidemia Are Co-Risk Factors for Atherosclerosis: Infection Prior to Induction of Hyperlipidemia Does Not Accelerate Development of Atherosclerotic Lesions in C57BL/6J Mice. by Blessing E, Campbell LA, Rosenfeld ME, Kuo CC.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=128267
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Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptordeficient, but not apolipoprotein E-deficient, mice. by Merkel M, Velez-Carrasco W, Hudgins LC, Breslow JL.; 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60864
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Comparison of m-mode echocardiographic left ventricular mass measured using digital and strip chart readings: The Atherosclerosis Risk in Communities (ARIC) study. by Arnett DK, Skelton TN, Liebson PR, Benjamin E, Hutchinson RG.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=198281
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De Novo Induction of Atherosclerosis by Chlamydia pneumoniae in a Rabbit Model. by Fong IW, Chiu B, Viira E, Jang D, Mahony JB.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96992
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Decreased atherosclerosis in CX3CR1 --/ -- mice reveals a role for fractalkine in atherogenesis. by Lesnik P, Haskell CA, Charo IF.; 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151849
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Decreased Atherosclerosis in Mice Deficient in Both Macrophage Colony-Stimulating Factor (op) and Apolipoprotein E. by Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M.; 1995 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41137
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Deficiency of cathepsin S reduces atherosclerosis in LDL receptor --deficient mice. by Sukhova GK, Zhang Y, Pan JH, Wada Y, Yamamoto T, Naito M, Kodama T, Tsimikas S, Witztum JL, Lu ML, Sakara Y, Chin MT, Libby P, Shi GP.; 2003 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153760
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Disruption of TGF-[beta] signaling in T cells accelerates atherosclerosis. by Robertson AK, Rudling M, Zhou X, Gorelik L, Flavell RA, Hansson GK.; 2003 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=228445
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Dramatically decreased high density lipoprotein cholesterol, increased remnant clearance, and insulin hypersensitivity in apolipoprotein A-II knockout mice suggest
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a complex role for apolipoprotein A-II in atherosclerosis susceptibility. by Weng W, Breslow JL.; 1996 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26214 •
Effect of Chlamydia trachomatis Infection on Atherosclerosis in Apolipoprotein EDeficient Mice. by Blessing E, Nagano S, Campbell LA, Rosenfeld ME, Kuo CC.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=97840
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Endothelin ETA receptor blockade restores NO-mediated endothelial function and inhibits atherosclerosis in apolipoprotein E-deficient mice. by Barton M, Haudenschild CC, d'Uscio LV, Shaw S, Munter K, Luscher TF.; 1998 Nov 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24379
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Expression of the peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. by Ricote M, Huang J, Fajas L, Li A, Welch J, Najib J, Witztum JL, Auwerx J, Palinski W, Glass CK.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22700
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Fibrinogen deficiency reduces vascular accumulation of apolipoprotein(a) and development of atherosclerosis in apolipoprotein(a) transgenic mice. by Lou XJ, Boonmark NW, Horrigan FT, Degen JL, Lawn RM.; 1998 Oct 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22875
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Functional CD40 ligand is expressed on human vascular endothelial cells, smooth muscle cells, and macrophages: Implications for CD40 --CD40 ligand signaling in atherosclerosis. by Mach F, Schonbeck U, Sukhova GK, Bourcier T, Bonnefoy JY, Pober JS, Libby P.; 1997 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20020
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Gene Targeting Approaches to Complex Genetic Diseases: Atherosclerosis and Essential Hypertension. by Smithies O, Maeda N.; 1995 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41675
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Genetic Engineering of Vein Grafts Resistant to Atherosclerosis. by Mann MJ, Gibbons GH, Kernoff RS, Diet FP, Tsao PS, Cooke JP, Kaneda Y, Dzau VJ.; 1995 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41972
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Hepatic lipase expression in macrophages contributes to atherosclerosis in apoEdeficient and LCAT-transgenic mice. by Nong Z, Gonzalez-Navarro H, Amar M, Freeman L, Knapper C, Neufeld EB, Paigen BJ, Hoyt RF, Fruchart-Najib J, SantamarinaFojo S.; 2003 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166288
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High-Grade Atherosclerosis of the Aorta. by Siddiqui MA, Holmberg MJ, Khan IA.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101274
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HIV protease inhibitors and atherosclerosis. by Hui DY.; 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151877
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How hyperglycemia promotes atherosclerosis: molecular mechanisms. by Aronson D, Rayfield EJ.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116615
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Human Apolipoprotein A-I Gene Expression Increases High Density Lipoprotein and Suppresses Atherosclerosis in the Apolipoprotein E-Deficient Mouse. by Plump AS, Scott CJ, Breslow JL.; 1994 Sep 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44862
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Identification of macrophage liver X receptors as inhibitors of atherosclerosis. by Tangirala RK, Bischoff ED, Joseph SB, Wagner BL, Walczak R, Laffitte BA, Daige CL, Thomas D, Heyman RA, Mangelsdorf DJ, Wang X, Lusis AJ, Tontonoz P, Schulman IG.; 2002 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129365
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Increased ABCA1 activity protects against atherosclerosis. by Singaraja RR, Fievet C, Castro G, James ER, Hennuyer N, Clee SM, Bissada N, Choy JC, Fruchart JC, McManus BM, Staels B, Hayden MR.; 2002 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151034
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Increased atherosclerosis in hyperlipidemic mice deficient in [alpha]-tocopherol transfer protein and vitamin E. by Terasawa Y, Ladha Z, Leonard SW, Morrow JD, Newland D, Sanan D, Packer L, Traber MG, Farese RV Jr.; 2000 Dec 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17661
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Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages. by Fazio S, Babaev VR, Murray AB, Hasty AH, Carter KJ, Gleaves LA, Atkinson JB, Linton MF.; 1997 Apr 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20778
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Inhibition of CD40 signaling limits evolution of established atherosclerosis in mice. by Schonbeck U, Sukhova GK, Shimizu K, Mach F, Libby P.; 2000 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16567
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Inhibition of NF-[kappa]B activation in macrophages increases atherosclerosis in LDL receptor --deficient mice. by Kanters E, Pasparakis M, Gijbels MJ, Vergouwe MN, Partouns-Hendriks I, Fijneman RJ, Clausen BE, Forster I, Kockx MM, Rajewsky K, Kraal G, Hofker MH, de Winther MP.; 2003 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=213488
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Intimal redox stress: Accelerated atherosclerosis in metabolic syndrome and type 2 diabetes mellitus. Atheroscleropathy. by Hayden MR, Tyagi SC.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140143
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Is Helicobacter pylori a Factor in Coronary Atherosclerosis? by Danesh J.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=84866
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Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues. by Van Eck M, Bos IS, Kaminski WE, Orso E, Rothe G, Twisk J, Bottcher A, Van Amersfoort ES, Christiansen-Weber TA, Fung-Leung WP, Van Berkel TJ, Schmitz G.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122943
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Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model. by Ludewig B, Freigang S, Jaggi M, Kurrer MO, Pei YC, Vlk L, Odermatt B, Zinkernagel RM, Hengartner H.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18836
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Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knockout mouse model. by Welch CL, Bretschger S, Latib N, Bezouevski M, Guo Y, Pleskac N, Liang CP, Barlow C, Dansky H, Breslow JL, Tall AR.; 2001 Jul 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=35448
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Low Density Lipoprotein Rich in Oleic Acid is Protected Against Oxidative Modification: Implications for Dietary Prevention of Atherosclerosis. by Parthasarathy S, Khoo JC, Miller E, Barnett J, Witztum JL, Steinberg D.; 1990 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54010
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Microembolic Signals in Patients Undergoing Coronary Artery Bypass Grafting: Effect of Aortic Atherosclerosis. by Kumral E, Balkir K, Yagdi T, Kara E, Evyapan D, Bilkay O.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101123
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Mutant Oocytic Low Density Lipoprotein Receptor Gene Family Member Causes Atherosclerosis and Female Sterility. by Bujo H, Yamamoto T, Hayashi K, Hermann M, Nimpf J, Schneider WJ.; 1995 Oct 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40911
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Overexpression of Lecithin:Cholesterol Acyltransferase in Transgenic Rabbits Prevents Diet-Induced Atherosclerosis. by Hoeg JM, Santamarina-Fojo S, Berard AM, Cornhill JF, Herderick EE, Feldman SH, Haudenschild CC, Vaisman BL, Hoyt RF, Demosky SJ, Kauffman RD, Hazel CM, Marcovina SM, Brewer HB.; 1996 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38077
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Plasminogen deficiency accelerates vessel wall disease in mice predisposed to atherosclerosis. by Xiao Q, Danton MJ, Witte DP, Kowala MC, Valentine MT, Bugge TH, Degen JL.; 1997 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23363
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Preclinical coronary atherosclerosis in a population with low incidence of myocardial infarction: cross sectional autopsy study. by Bertomeu A, Garcia-Vidal O, Farre X, Galobart A, Vazquez M, Laguna JC, Ros E.; 2003 Sep 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194083
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Promotion of Vascular Smooth Muscle Cell Growth by Homocysteine: A Link to Atherosclerosis. by Tsai J, Perrella MA, Yashizumi M, Hsieh C, Haber E, Schlegel R, Lee M.; 1994 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44203
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Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice. by Caligiuri G, Nicoletti A, Poirier B, Hansson GK.; 2002 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150903
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Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor. by Claudel T, Leibowitz MD, Fievet C, Tailleux A, Wagner B, Repa JJ, Torpier G, Lobaccaro JM, Paterniti JR, Mangelsdorf DJ, Heyman RA, Auwerx J.; 2001 Feb 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30186
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Risk factors in coronary atherosclerosis athero-inflammation: the meeting point. by Altman R.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179880
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Splenic immunity and atherosclerosis: a glimpse into a novel paradigm? by Witztum JL.; 2002 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150921
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Superoxide and Peroxynitrite in Atherosclerosis. by White CR, Brock TA, Chang L, Crapo J, Briscoe P, Ku D, Bradley WA, Gianturco SH, Gore J, Freeman BA, Tarpey MM.; 1994 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43090
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Suppression of Diet-Induced Atherosclerosis in Low Density Lipoprotein Receptor Knockout Mice Overexpressing Lipoprotein Lipase. by Shimada M, Ishibashi S, Inaba T, Yagyu H, Harada K, Osuga J, Ohashi K, Yazaki Y, Yamada N.; 1996 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38967
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Synthetic LXR ligand inhibits the development of atherosclerosis in mice. by Joseph SB, McKilligin E, Pei L, Watson MA, Collins AR, Laffitte BA, Chen M, Noh G, Goodman J, Hagger GN, Tran J, Tippin TK, Wang X, Lusis AJ, Hsueh WA, Law RE, Collins JL, Willson TM, Tontonoz P.; 2002 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124297
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Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: Implications in atherosclerosis. by Mukherjee TK, Dinh H, Chaudhuri G, Nathan L.; 2002 Mar 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122647
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The ATP binding cassette transporter A1 (ABCA1) modulates the development of aortic atherosclerosis in C57BL /6 and apoE-knockout mice. by Joyce CW, Amar MJ, Lambert G, Vaisman BL, Paigen B, Najib-Fruchart J, Hoyt RF Jr, Neufeld ED, Remaley AT, Fredrickson DS, Brewer HB Jr, Santamarina-Fojo S.; 2002 Jan 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117573
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Transgenic Mouse Models of Lipoprotein Metabolism and Atherosclerosis. by Breslow JL.; 1993 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47346
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 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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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 atherosclerosis, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “atherosclerosis” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for atherosclerosis (hyperlinks lead to article summaries): •
34th Bethesda Conference: Executive summary--can atherosclerosis imaging techniques improve the detection of patients at risk for ischemic heart disease? Author(s): Taylor AJ, Merz CN, Udelson JE. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 1860-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798552&dopt=Abstract
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34th Bethesda Conference: Task force #2--What is the pathologic basis for new atherosclerosis imaging techniques? Author(s): Burke AP, Virmani R, Galis Z, Haudenschild CC, Muller JE. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 1874-86. Review. Erratum In: J Am Coll Cardiol. 2003 September 17; 42(6): 1147. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798554&dopt=Abstract
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34th Bethesda Conference: Task force #3--What is the spectrum of current and emerging techniques for the noninvasive measurement of atherosclerosis? Author(s): Redberg RF, Vogel RA, Criqui MH, Herrington DM, Lima JA, Roman MJ. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 1886-98. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798555&dopt=Abstract
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34th Bethesda Conference: Task force #4--How do we select patients for atherosclerosis imaging? Author(s): Wilson PW, Smith SC Jr, Blumenthal RS, Burke GL, Wong ND. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 1898-906. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798556&dopt=Abstract
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34th Bethesda Conference: Task force #5--Is atherosclerosis imaging cost effective? Author(s): Mark DB, Shaw LJ, Lauer MS, O'Malley PG, Heidenreich P. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 1906-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798557&dopt=Abstract
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A link between Helicobacter pylori and/or Chlamydia spp. infections and atherosclerosis. Author(s): Chmiela M, Kowalewicz-Kulbat M, Miszczak A, Wisniewska M, Rechcinski T, Kolodziej K, Kasprzak J, Wadstrom T, Rudnicka W. Source: Fems Immunology and Medical Microbiology. 2003 May 25; 36(3): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738390&dopt=Abstract
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A model of primary atherosclerosis and post-angioplasty restenosis in mice. Author(s): Leidenfrost JE, Khan MF, Boc KP, Villa BR, Collins ET, Parks WC, Abendschein DR, Choi ET. Source: American Journal of Pathology. 2003 August; 163(2): 773-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875996&dopt=Abstract
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A novel cellular marker of insulin resistance and early atherosclerosis in humans is related to impaired fat cell differentiation and low adiponectin. Author(s): Jansson PA, Pellme F, Hammarstedt A, Sandqvist M, Brekke H, Caidahl K, Forsberg M, Volkmann R, Carvalho E, Funahashi T, Matsuzawa Y, Wiklund O, Yang X, Taskinen MR, Smith U. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 August; 17(11): 1434-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890697&dopt=Abstract
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Accelerated atherosclerosis. Author(s): Samra SS, Walwaikar PP, Morye VK, Gawde AG. Source: J Indian Med Assoc. 2002 August; 100(8): 516, 518-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675186&dopt=Abstract
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Acute coronary syndromes, plaque vulnerability, and carotid artery disease: the changing role of atherosclerosis imaging. Author(s): Tuzcu EM, Schoenhagen P. Source: Journal of the American College of Cardiology. 2003 September 17; 42(6): 1033-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678926&dopt=Abstract
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Adult-onset growth hormone deficiency: Relation of postprandial dyslipidemia to premature atherosclerosis. Author(s): Twickler TB, Cramer MJ, Dallinga-Thie GM, Chapman MJ, Erkelens DW, Koppeschaar HP. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2479-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788843&dopt=Abstract
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Aggressive treatment of atherosclerosis: the time is now. Author(s): Fonarow GC. Source: Cleve Clin J Med. 2003 May; 70(5): 431-4, 437-8, 440. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785316&dopt=Abstract
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Aging of progenitor cells contributes to atherosclerosis. Author(s): SoRelle R. Source: Circulation. 2003 July 29; 108(4): E9006-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885741&dopt=Abstract
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An association between atherosclerosis and venous thrombosis. Author(s): Tai YF. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 401-2; Author Reply 401-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879890&dopt=Abstract
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An association between atherosclerosis and venous thrombosis. Author(s): Duggirala MK, Cook DA, Mauck KF. Source: The New England Journal of Medicine. 2003 July 24; 349(4): 401-2; Author Reply 401-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878750&dopt=Abstract
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An association between atherosclerosis and venous thrombosis. Author(s): Prandoni P, Bilora F, Marchiori A, Bernardi E, Petrobelli F, Lensing AW, Prins MH, Girolami A. Source: The New England Journal of Medicine. 2003 April 10; 348(15): 1435-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686699&dopt=Abstract
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An early and sustained peripheral inflammatory response in acute ischaemic stroke: relationships with infection and atherosclerosis. Author(s): Emsley HC, Smith CJ, Gavin CM, Georgiou RF, Vail A, Barberan EM, Hallenbeck JM, del Zoppo GJ, Rothwell NJ, Tyrrell PJ, Hopkins SJ. Source: Journal of Neuroimmunology. 2003 June; 139(1-2): 93-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799026&dopt=Abstract
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Androgens up-regulate atherosclerosis-related genes in macrophages from males but not females: molecular insights into gender differences in atherosclerosis. Author(s): Ng MK, Quinn CM, McCrohon JA, Nakhla S, Jessup W, Handelsman DJ, Celermajer DS, Death AK. Source: Journal of the American College of Cardiology. 2003 October 1; 42(7): 1306-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14522500&dopt=Abstract
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Aortic atherosclerosis and postoperative neurological dysfunction in elderly coronary surgical patients. Author(s): Goto T, Baba T, Matsuyama K, Honma K, Ura M, Koshiji T. Source: The Annals of Thoracic Surgery. 2003 June; 75(6): 1912-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12822635&dopt=Abstract
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Apolipoprotein E: possible therapeutic target for atherosclerosis. Author(s): Bocksch L, Stephens T, Lucas A, Singh B. Source: Current Drug Targets. Cardiovascular & Haematological Disorders. 2001 December; 1(2): 93-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12769659&dopt=Abstract
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Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Author(s): Del Rincon I, Williams K, Stern MP, Freeman GL, O'Leary DH, Escalante A. Source: Arthritis and Rheumatism. 2003 July; 48(7): 1833-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847676&dopt=Abstract
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Association between coronary artery atherosclerosis and the intima-media thickness of the common carotid artery measured on ultrasonography. Author(s): Rosa EM, Kramer C, Castro I. Source: Arquivos Brasileiros De Cardiologia. 2003 June; 80(6): 589-92, 285-8. Epub 2003 July 02. English, Portuguese. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856069&dopt=Abstract
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Association between offspring birth weight and atherosclerosis in middle aged men and women: British Regional Heart Study. Author(s): Lawlor DA, Davey Smith G, Whincup P, Wannamethee G, Papacosta O, Dhanjil S, Griffin M, Nicolaides AN, Ebrahim S. Source: Journal of Epidemiology and Community Health. 2003 June; 57(6): 462-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775796&dopt=Abstract
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Association of an allelic variant of interleukin-6 with subclinical carotid atherosclerosis in an Australian community population. Author(s): Chapman CM, Beilby JP, Humphries SE, Palmer LJ, Thompson PL, Hung J. Source: European Heart Journal. 2003 August; 24(16): 1494-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12919773&dopt=Abstract
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Association of methylenetetrahydrofolate reductase gene polymorphism with carotid atherosclerosis depending on smoking status in a Japanese general population. Author(s): Inamoto N, Katsuya T, Kokubo Y, Mannami T, Asai T, Baba S, Ogata J, Tomoike H, Ogihara T. Source: Stroke; a Journal of Cerebral Circulation. 2003 July; 34(7): 1628-33. Epub 2003 May 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775885&dopt=Abstract
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Associations of whole-grain, refined-grain, and fruit and vegetable consumption with risks of all-cause mortality and incident coronary artery disease and ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study. Author(s): Steffen LM, Jacobs DR Jr, Stevens J, Shahar E, Carithers T, Folsom AR. Source: The American Journal of Clinical Nutrition. 2003 September; 78(3): 383-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12936919&dopt=Abstract
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Atherosclerosis and HIV in the highly active antiretroviral therapy era: towards an epidemic of cardiovascular disease? Author(s): Mooser V. Source: Aids (London, England). 2003 April; 17 Suppl 1: S65-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870532&dopt=Abstract
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Atherosclerosis and HIV infection: diagnosis and treatment. Author(s): Mooser V. Source: Adv Cardiol. 2003; 40: 140-50. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14533551&dopt=Abstract
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Atherosclerosis and secondary deep vein thrombosis: a difficult correlation. Author(s): Bilora F, Boccioletti V, Petrobelli F, Girolami A. Source: Clinical and Applied Thrombosis/Hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2003 April; 9(2): 121-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12812380&dopt=Abstract
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Atherosclerosis in patients with end-stage renal failure prior to initiation of hemodialysis. Author(s): Hojs R, Hojs-Fabjan T, Balon BP. Source: Renal Failure. 2003 March; 25(2): 247-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739831&dopt=Abstract
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Atherosclerosis in premenopausal women with antiphospholipid syndrome and systemic lupus erythematosus: a controlled study. Author(s): Vlachoyiannopoulos PG, Kanellopoulos PG, Ioannidis JP, Tektonidou MG, Mastorakou I, Moutsopoulos HM. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 645-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709540&dopt=Abstract
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Atherosclerosis of carotid and intracranial arteries. Author(s): Rollo M, Tartaglione T, Pedicelli A, Settecasi C. Source: Rays. 2001 October-December; 26(4): 247-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696280&dopt=Abstract
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Atherosclerosis target of lipid-lowering therapy: is lower LDL cholesterol better? Author(s): Jones PH. Source: Am J Manag Care. 2003 August; Suppl: 1, 4-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678393&dopt=Abstract
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Atherosclerosis: an inflammatory disease. Author(s): Liuzzo G. Source: Rays. 2001 October-December; 26(4): 221-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696277&dopt=Abstract
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Autoantibody-mediated atherosclerosis. Author(s): Matsuura E, Kobayashi K, Koike T, Shoenfeld Y. Source: Autoimmunity Reviews. 2002 December; 1(6): 348-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848990&dopt=Abstract
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Baseline health-related quality of life in postmenopausal women with coronary heart disease: the Estrogen Replacement and Atherosclerosis (ERA) trial. Author(s): Sherman AM, Shumaker SA, Kancler C, Zheng B, Reboussin DM, Legault C, Herrington DM; ERA Trial Investigators. Source: Journal of Women's Health (2002). 2003 May; 12(4): 351-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804342&dopt=Abstract
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Blood pressure, atherosclerosis, and the incidence of age-related maculopathy: the Rotterdam Study. Author(s): van Leeuwen R, Ikram MK, Vingerling JR, Witteman JC, Hofman A, de Jong PT. Source: Investigative Ophthalmology & Visual Science. 2003 September; 44(9): 3771-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939290&dopt=Abstract
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Body satisfaction in 8-year-old children after long-term dietary counseling in a prospective randomized atherosclerosis prevention trial. Author(s): Saarilehto S, Lapinleimu H, Keskinen S, Helenius H, Simell O. Source: Archives of Pediatrics & Adolescent Medicine. 2003 August; 157(8): 753-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912780&dopt=Abstract
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Bone mineral density may be related to atherosclerosis in hemodialysis patients. Author(s): Nakashima A, Yorioka N, Tanji C, Asakimori Y, Ago R, Usui K, Shigemoto K, Harada S. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 June; 14(5): 369-73. Epub 2003 May 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768278&dopt=Abstract
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Calcific aortic stenosis: another face of atherosclerosis? Author(s): Novaro GM, Griffin BP. Source: Cleve Clin J Med. 2003 May; 70(5): 471-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12779138&dopt=Abstract
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Can angiotensin-converting enzyme inhibitors reverse atherosclerosis? Author(s): Higgins JP. Source: Southern Medical Journal. 2003 June; 96(6): 569-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12938784&dopt=Abstract
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Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis. Author(s): deFilippi C, Wasserman S, Rosanio S, Tiblier E, Sperger H, Tocchi M, Christenson R, Uretsky B, Smiley M, Gold J, Muniz H, Badalamenti J, Herzog C, Henrich W. Source: Jama : the Journal of the American Medical Association. 2003 July 16; 290(3): 353-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12865376&dopt=Abstract
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Cardiovascular autonomic neuropathy associated with carotid atherosclerosis in Type 2 diabetic patients. Author(s): Gottsater A, Ryden-Ahlgren A, Szelag B, Hedblad B, Persson J, Berglund G, Wroblewski M, Sundkvist G. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 June; 20(6): 495-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12786687&dopt=Abstract
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Cardiovascular risk factors and atherosclerosis in young males: ARMY study (Atherosclerosis Risk-Factors in Male Youngsters). Author(s): Knoflach M, Kiechl S, Kind M, Said M, Sief R, Gisinger M, van der Zee R, Gaston H, Jarosch E, Willeit J, Wick G. Source: Circulation. 2003 September 2; 108(9): 1064-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12952827&dopt=Abstract
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Cardiovascular risk factors and increased carotid intima-media thickness in healthy young adults: the Atherosclerosis Risk in Young Adults (ARYA) Study. Author(s): Oren A, Vos LE, Uiterwaal CS, Grobbee DE, Bots ML. Source: Archives of Internal Medicine. 2003 August 11-25; 163(15): 1787-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912713&dopt=Abstract
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Carotid atherosclerosis and coronary heart disease in the metabolic syndrome: prospective data from the Bruneck study. Author(s): Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Bonadonna RC, Muggeo M; Bruneck study. Source: Diabetes Care. 2003 April; 26(4): 1251-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663606&dopt=Abstract
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CD40 ligand is selectively expressed on CD4+ T cells and platelets: implications for CD40-CD40L signalling in atherosclerosis. Author(s): Buchner K, Henn V, Grafe M, de Boer OJ, Becker AE, Kroczek RA. Source: The Journal of Pathology. 2003 October; 201(2): 288-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14517846&dopt=Abstract
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Cell-associated and extracellular phospholipid transfer protein in human coronary atherosclerosis. Author(s): O'Brien KD, Vuletic S, McDonald TO, Wolfbauer G, Lewis K, Tu AY, Marcovina S, Wight TN, Chait A, Albers JJ. Source: Circulation. 2003 July 22; 108(3): 270-4. Epub 2003 June 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835223&dopt=Abstract
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Cellular origins of atherosclerosis: towards ontogenetic endgame? Author(s): Doherty TM, Shah PK, Rajavashisth TB. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2003 April; 17(6): 592-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665471&dopt=Abstract
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Cerebral atherosclerosis and mild Alzheimer's disease. Author(s): Rafael H. Source: Stroke; a Journal of Cerebral Circulation. 2003 August; 34(8): E106. Epub 2003 July 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855821&dopt=Abstract
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Cervical and intracranial atherosclerosis and silent brain infarction in Japanese patients with coronary artery disease. Author(s): Uekita K, Hasebe N, Funayama N, Aoyama H, Kuroda K, Aizawa H, Kataoka R, Kikuchi K. Source: Cerebrovascular Diseases (Basel, Switzerland). 2003; 16(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766364&dopt=Abstract
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Characterization of polymorphic structure of SREBP-2 gene: role in atherosclerosis. Author(s): Robinet P, Vedie B, Chironi G, Gariepy J, Simon A, Moatti N, Paul JL. Source: Atherosclerosis. 2003 June; 168(2): 381-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801623&dopt=Abstract
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Chemokine receptor 2 (CCR2) in atherosclerosis, infectious diseases, and regulation of T-cell polarization. Author(s): Charo IF, Peters W. Source: Microcirculation (New York, N.Y. : 1994). 2003 June; 10(3-4): 259-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851643&dopt=Abstract
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Chlamydia pneumoniae, antibiotic treatment, and early atherosclerosis. Author(s): Liuba P, Pesonen E, Paakkari I. Source: Circulation. 2003 June 10; 107(22): E205; Author Reply E205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796417&dopt=Abstract
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Cholesterol-fed ovariectomized monkeys are good animal models for human atherosclerosis of postmenopausal women. Author(s): Torii R, Shiomi M, Ito T, Yamada S, Eguchi Y, Ikeda N. Source: Primates; Journal of Primatology. 2003 July; 44(3): 247-52. Epub 2003 April 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884115&dopt=Abstract
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Clinical significance of high-density lipoproteins and the development of atherosclerosis: focus on the role of the adenosine triphosphate-binding cassette protein A1 transporter. Author(s): Brewer HB Jr, Santamarina-Fojo S. Source: The American Journal of Cardiology. 2003 August 21; 92(4B): 10K-16K. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948871&dopt=Abstract
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Comparison between measures of atherosclerosis and risk of stroke: the Rotterdam Study. Author(s): Hollander M, Hak AE, Koudstaal PJ, Bots ML, Grobbee DE, Hofman A, Witteman JC, Breteler MM. Source: Stroke; a Journal of Cerebral Circulation. 2003 October; 34(10): 2367-72. Epub 2003 September 04. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12958327&dopt=Abstract
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Coronary atherosclerosis and body iron stores. Author(s): Auer J, Berent R, Weber T, Eber B. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1848-9; Author Reply 1849-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767679&dopt=Abstract
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Covalent binding of oxidized cholesteryl esters to protein: implications for oxidative modification of low density lipoprotein and atherosclerosis. Author(s): Kawai Y, Saito A, Shibata N, Kobayashi M, Yamada S, Osawa T, Uchida K. Source: The Journal of Biological Chemistry. 2003 June 6; 278(23): 21040-9. Epub 2003 March 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663661&dopt=Abstract
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Cyclooxygenase-2 inhibitors and atherosclerosis. Author(s): Belton O, Fitzgerald D. Source: Journal of the American College of Cardiology. 2003 May 21; 41(10): 1820-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767670&dopt=Abstract
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Detection of Chlamydiae pneumoniae but not Helicobacter pylori DNA in atherosclerosis plaques. Author(s): Dore MP, Sepulveda AR, Bacciu PP, Blasi F, Simula L, Marras L, Piccolo D, Cherchi GB, Graham DY, Realdi G. Source: Digestive Diseases and Sciences. 2003 May; 48(5): 945-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12772795&dopt=Abstract
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Detection of early carotid arterial atherosclerosis by briefly trained physicians using a hand-held ultrasound device. Author(s): Kimura BJ, Fowler SJ, Nguyen DT, Amundson SA, DeMaria AN. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 239-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860236&dopt=Abstract
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Determination of plasma concentrations of endothelin-1(1-31) and endothelin-1 in healthy subjects and patients with atherosclerosis. Author(s): Suzaki Y, Yoshizumi M, Yamashita Y, Abe S, Tsuchiya K, Satoh Y, Kuroda Y, Horike K, Kano M, Fukata Y, Kitaichi T, Hori T, Masuda Y, Kitagawa T, Minakuchi K, Tamaki T. Source: Journal of Cardiovascular Pharmacology. 2003 January; 41 Suppl 1: S83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688403&dopt=Abstract
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Development of atherosclerosis and infectious agents. Author(s): Yamamoto M. Source: Intern Med. 2003 July; 42(7): 547-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12879941&dopt=Abstract
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Diagnostic imaging in lower limb atherosclerosis. Author(s): Di Stasi C, Cina A, Manfredi R, Colafati S. Source: Rays. 2001 October-December; 26(4): 277-89. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696282&dopt=Abstract
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Donor-transmitted coronary atherosclerosis. Author(s): Grauhan O, Patzurek J, Hummel M, Lehmkuhl H, Dandel M, Pasic M, Weng Y, Hetzer R. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 2003 May; 22(5): 568-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742420&dopt=Abstract
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Early carotid atherosclerosis in normotensive severe obese premenopausal women with low DHEA(S). Author(s): Savastano S, Valentino R, Belfiore A, De Luca N, de Alteriis A, Orio F Jr, Palomba S, Villani AM, Falcone C, Lupoli G, Lombardi G. Source: J Endocrinol Invest. 2003 March; 26(3): 236-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809174&dopt=Abstract
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Echocardiographic left ventricular mass in African-Americans: the Jackson cohort of the Atherosclerosis Risk in Communities Study. Author(s): Skelton TN, Andrew ME, Arnett DK, Burchfiel CM, Garrison RJ, Samdarshi TE, Taylor HA, Hutchinson RG. Source: Echocardiography (Mount Kisco, N.Y.). 2003 February; 20(2): 111-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12848675&dopt=Abstract
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Effect of long-term hormone replacement therapy on atherosclerosis progression in postmenopausal women relates to myeloperoxidase promoter polymorphism. Author(s): Makela R, Dastidar P, Jokela H, Saarela M, Punnonen R, Lehtimaki T. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3823-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915675&dopt=Abstract
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Effects of long term cholesterol lowering on coronary atherosclerosis in patient risk factor subgroups: the Simvastatin/enalapril Coronary Atherosclerosis Trial (SCAT). Author(s): Burton JR, Teo KK, Buller CE, Plante S, Catellier D, Tymchak W, Taylor D, Dzavik V, Montague TJ; SCAT investigators. Source: The Canadian Journal of Cardiology. 2003 April; 19(5): 487-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12717482&dopt=Abstract
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Effects of testosterone administration on fat distribution, insulin sensitivity, and atherosclerosis progression. Author(s): Bhasin S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003; 37 Suppl 2: S142-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942389&dopt=Abstract
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Egr-1, a major link between infection and atherosclerosis? Author(s): Rupp J, Maass M. Source: Circulation Research. 2003 May 16; 92(9): E78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750307&dopt=Abstract
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Emerging non-statin LDL-lowering therapies for dyslipidemia and atherosclerosis. Author(s): Shah PK. Source: Reviews in Cardiovascular Medicine. 2003 Summer; 4(3): 136-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949442&dopt=Abstract
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Endothelial progenitor cells are decreased in blood of cardiac allograft patients with vasculopathy and endothelial cells of noncardiac origin are enriched in transplant atherosclerosis. Author(s): Simper D, Wang S, Deb A, Holmes D, McGregor C, Frantz R, Kushwaha SS, Caplice NM. Source: Circulation. 2003 July 15; 108(2): 143-9. Epub 2003 June 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12835206&dopt=Abstract
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Epiaortic ultrasound and intraoperative transesophageal ecocardiography for the thoracic aorta atherosclerosis assessment in patient undergoing CABG. Surgical technique modification to avoid cerebral stroke. Author(s): Gaspar M, Laufer G, Bonatti J, Muller L, Mair P. Source: Chirurgia (Bucur). 2002 November-December; 97(6): 529-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12731210&dopt=Abstract
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Epilepsy, atherosclerosis, myocardial infarction, and carbamazepine. Author(s): de Chadarevian JP, Legido A, Miles DK, Katsetos CD. Source: Journal of Child Neurology. 2003 February; 18(2): 150-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693787&dopt=Abstract
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Epistatic interaction between variations in the angiotensin I converting enzyme and angiotensin II type 1 receptor genes in relation to extent of coronary atherosclerosis. Author(s): Ye S, Dhillon S, Seear R, Dunleavey L, Day LB, Bannister W, Day IN, Simpson I. Source: Heart (British Cardiac Society). 2003 October; 89(10): 1195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12975417&dopt=Abstract
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Evolving atherosclerosis at carotid and intracranial arteries in Japanese patients with ischemic heart disease: a 5-year longitudinal study with MR angiography. Author(s): Uehara T, Tabuchi M, Mori E, Yamadori A. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2003 September; 10(5): 507-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12940830&dopt=Abstract
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Factors associated with accelerated atherosclerosis in HIV-1-infected persons treated with protease inhibitors. Author(s): Lai S, Lai H, Celentano DD, Vlahov D, Ren S, Margolick J, Lima JA, Bartlett JG. Source: Aids Patient Care and Stds. 2003 May; 17(5): 211-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816615&dopt=Abstract
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Failure to detect Chlamydia pneumoniae by cell culture and polymerase chain reaction in major arteries of 93 patients with atherosclerosis. Author(s): Bishara J, Pitlik S, Kazakov A, Sahar G, Haddad M, Vojdani A, Rosenberg S, Samra Z. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 May; 22(5): 300-2. Epub 2003 May 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12739106&dopt=Abstract
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Genetic approaches in the clinical investigation of complex disorders: malnutrition, inflammation, and atherosclerosis (MIA) as a prototype. Author(s): Pecoits-Filho R, Nordfors L, Lindholm B, Hoff CM, Schalling M, Stenvinkel P. Source: Kidney International. Supplement. 2003 May; (84): S162-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694336&dopt=Abstract
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Genetic instability, DNA damage and atherosclerosis. Author(s): Andreassi MG, Botto N. Source: Cell Cycle (Georgetown, Tex.). 2003 May-June; 2(3): 224-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734429&dopt=Abstract
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HDL in atherosclerosis: actor or bystander? Author(s): Asztalos BF, Schaefer EJ. Source: Atherosclerosis. Supplements. 2003 March; 4(1): 21-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714034&dopt=Abstract
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High density lipoproteins (HDLs) and atherosclerosis; the unanswered questions. Author(s): Barter P, Kastelein J, Nunn A, Hobbs R; Future Forum Editorial Board. Source: Atherosclerosis. 2003 June; 168(2): 195-211. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801602&dopt=Abstract
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High glucose alters matrix metalloproteinase expression in two key vascular cells: potential impact on atherosclerosis in diabetes. Author(s): Death AK, Fisher EJ, McGrath KC, Yue DK. Source: Atherosclerosis. 2003 June; 168(2): 263-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801609&dopt=Abstract
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High transport and malnutrition-inflammation-atherosclerosis (MIA) syndrome. Author(s): Heaf J. Source: Perit Dial Int. 2003 March-April; 23(2): 109-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12713074&dopt=Abstract
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Higher prevalence of Chlamydia pneumoniae seropositivity in Finnish twins compared with co-twins living in Sweden: relationships with markers of subclinical atherosclerosis. Author(s): Jartti L, Raitakari OT, Jarvisalo MJ, Hammar N, Kaprio J, Koskenvuo M, Marniemi J, Saikku P, Ronnemaa T. Source: Clinical Science (London, England : 1979). 2003 September; 105(3): 303-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747799&dopt=Abstract
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Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women. Author(s): Hodis HN, Mack WJ, Azen SP, Lobo RA, Shoupe D, Mahrer PR, Faxon DP, Cashin-Hemphill L, Sanmarco ME, French WJ, Shook TL, Gaarder TD, Mehra AO, Rabbani R, Sevanian A, Shil AB, Torres M, Vogelbach KH, Selzer RH; Women's Estrogen-Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial Research Group. Source: The New England Journal of Medicine. 2003 August 7; 349(6): 535-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904518&dopt=Abstract
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Hypothyroidism and atherosclerosis. Author(s): Cappola AR, Ladenson PW. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2438-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788839&dopt=Abstract
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Images in cardiovascular medicine. Focal coronary atherosclerosis proximal to myocardial bridging. Author(s): Schunkert H. Source: Circulation. 2003 April 15; 107(14): 1944. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695284&dopt=Abstract
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Imaging of aortic atherosclerosis. Author(s): Meduri A, Natale L, Marano P. Source: Rays. 2001 October-December; 26(4): 237-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696279&dopt=Abstract
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Immune responses to heat shock protein in Porphyromonas gingivalis-infected periodontitis and atherosclerosis patients. Author(s): Chung SW, Kang HS, Park HR, Kim SJ, Kim SJ, Choi JI. Source: Journal of Periodontal Research. 2003 August; 38(4): 388-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12828655&dopt=Abstract
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Immunomodulation for treatment and prevention of atherosclerosis. Author(s): Sherer Y, Shoenfeld Y. Source: Autoimmunity Reviews. 2002 February; 1(1-2): 21-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849054&dopt=Abstract
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Implication of earlier carotid atherosclerosis for stroke and its subtypes. Author(s): Nagai Y, Kitagawa K, Matsumoto M. Source: Preventive Cardiology. 2003 Spring; 6(2): 99-103. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732796&dopt=Abstract
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Increased pulse wave velocity associated with reduced calcaneal quantitative osteosono index: possible relationship between atherosclerosis and osteopenia. Author(s): Hirose K, Tomiyama H, Okazaki R, Arai T, Koji Y, Zaydun G, Hori S, Yamashina A. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2573-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788857&dopt=Abstract
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Inflammation and atherosclerosis: mechanisms underlying vulnerable plaque. Author(s): Krams R, Segers D, Gourabi BM, Maat W, Cheng C, van Pelt C, van Damme LC, de Feyter P, van der Steen T, de Korte CL, Serruys PW. Source: Journal of Interventional Cardiology. 2003 April; 16(2): 107-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768913&dopt=Abstract
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Inflammation and emerging risk factors in diabetes mellitus and atherosclerosis. Author(s): Theuma P, Fonseca VA. Source: Curr Diab Rep. 2003 June; 3(3): 248-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762974&dopt=Abstract
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Inflammation in atherosclerosis: causal or casual? The need for randomized trials. Author(s): Meir K, Leitersdorf E, Hennekens CH. Source: American Heart Journal. 2003 August; 146(2): 199-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891182&dopt=Abstract
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Inflammation, infection, and atherosclerosis. Author(s): Fahdi IE, Gaddam V, Garza L, Romeo F, Mehta JL. Source: Brain, Behavior, and Immunity. 2003 August; 17(4): 238-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831825&dopt=Abstract
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Inflammatory and thrombotic mechanisms in coronary atherosclerosis. Author(s): Tousoulis D, Davies G, Stefanadis C, Toutouzas P, Ambrose JA. Source: Heart (British Cardiac Society). 2003 September; 89(9): 993-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923007&dopt=Abstract
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Inflammatory reactions in the pathogenesis of atherosclerosis. Author(s): Fan J, Watanabe T. Source: J Atheroscler Thromb. 2003; 10(2): 63-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740479&dopt=Abstract
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Influences of matrix metalloproteinase-3 gene variation on extent of coronary atherosclerosis and risk of myocardial infarction. Author(s): Beyzade S, Zhang S, Wong YK, Day IN, Eriksson P, Ye S. Source: Journal of the American College of Cardiology. 2003 June 18; 41(12): 2130-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821236&dopt=Abstract
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Insulin resistance and atherosclerosis in branch retinal vein occlusion. Author(s): Ogawa O, Onuma T, Uchino H, Takayanagi Y, Tanaka Y, Yamasaki Y, Atsumi Y, Matsuoka K, Kawamori R. Source: Japanese Journal of Ophthalmology. 2003 July-August; 47(4): 351-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842202&dopt=Abstract
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Interrelationship between peripheral arterial occlusive disease, carotid atherosclerosis and flow mediated dilation of the brachial artery. Author(s): Poredos P, Golob M, Jensterle M. Source: International Angiology : a Journal of the International Union of Angiology. 2003 March; 22(1): 83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771862&dopt=Abstract
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Intracranial atherosclerosis. Author(s): Kappelle LJ. Source: Adv Neurol. 2003; 92: 65-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760167&dopt=Abstract
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Inverse relationship between serum bilirubin and atherosclerosis in men: a metaanalysis of published studies. Author(s): Novotny L, Vitek L. Source: Experimental Biology and Medicine (Maywood, N.J.). 2003 May; 228(5): 568-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709588&dopt=Abstract
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Is aortic dilatation an atherosclerosis-related process? Clinical, laboratory, and transesophageal echocardiographic correlates of thoracic aortic dimensions in the population with implications for thoracic aortic aneurysm formation. Author(s): Agmon Y, Khandheria BK, Meissner I, Schwartz GL, Sicks JD, Fought AJ, O'Fallon WM, Wiebers DO, Tajik AJ. Source: Journal of the American College of Cardiology. 2003 September 17; 42(6): 107683. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678934&dopt=Abstract
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Leisure time physical activity and early atherosclerosis: the Los Angeles Atherosclerosis Study. Author(s): Nordstrom CK, Dwyer KM, Merz CN, Shircore A, Dwyer JH. Source: The American Journal of Medicine. 2003 July; 115(1): 19-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867230&dopt=Abstract
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Leukaemia inhibitory factor retards the progression of atherosclerosis. Author(s): Rolfe BE, Stamatiou S, World CJ, Brown L, Thomas AC, Bingley JA, Worth NF, Campbell JH. Source: Cardiovascular Research. 2003 April 1; 58(1): 222-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667965&dopt=Abstract
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Long term effects of nisoldipine on the progression of coronary atherosclerosis and the occurrence of clinical events: the NICOLE study. Author(s): Dens JA, Desmet WJ, Coussement P, De Scheerder IK, Kostopoulos K, Kerdsinchai P, Supanantaroek C, Piessens JH. Source: Heart (British Cardiac Society). 2003 August; 89(8): 887-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860866&dopt=Abstract
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Long-term mortality and recurrent stroke risk among Chinese stroke patients with predominant intracranial atherosclerosis. Author(s): Wong KS, Li H. Source: Stroke; a Journal of Cerebral Circulation. 2003 October; 34(10): 2361-6. Epub 2003 August 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947158&dopt=Abstract
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Long-term stable expression of human apolipoprotein A-I mediated by helperdependent adenovirus gene transfer inhibits atherosclerosis progression and remodels atherosclerotic plaques in a mouse model of familial hypercholesterolemia. Author(s): Belalcazar LM, Merched A, Carr B, Oka K, Chen KH, Pastore L, Beaudet A, Chan L. Source: Circulation. 2003 June 3; 107(21): 2726-32. Epub 2003 May 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742997&dopt=Abstract
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Loss of bone marrow-derived vascular progenitor cells leads to inflammation and atherosclerosis. Author(s): Goldschmidt-Clermont PJ. Source: American Heart Journal. 2003 October; 146(4 Suppl): S5-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564300&dopt=Abstract
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Low-grade systemic inflammation and the development of type 2 diabetes: the atherosclerosis risk in communities study. Author(s): Duncan BB, Schmidt MI, Pankow JS, Ballantyne CM, Couper D, Vigo A, Hoogeveen R, Folsom AR, Heiss G; Atherosclerosis Risk in Communities Study. Source: Diabetes. 2003 July; 52(7): 1799-805. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829649&dopt=Abstract
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LXRs: new therapeutic targets in atherosclerosis? Author(s): Joseph SB, Tontonoz P. Source: Current Opinion in Pharmacology. 2003 April; 3(2): 192-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681243&dopt=Abstract
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Magnetic resonance imaging of coronary atherosclerosis. Author(s): Fayad ZA, Choudhury RP, Fuster V. Source: Current Atherosclerosis Reports. 2003 September; 5(5): 411-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12911852&dopt=Abstract
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Metabolic predictors of 5-year change in weight and waist circumference in a triethnic population: the insulin resistance atherosclerosis study. Author(s): Mayer-Davis EJ, Kirkner GJ, Karter AJ, Zaccaro DJ. Source: American Journal of Epidemiology. 2003 April 1; 157(7): 592-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672678&dopt=Abstract
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Minireview: The adipocyte--at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Author(s): Rajala MW, Scherer PE. Source: Endocrinology. 2003 September; 144(9): 3765-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12933646&dopt=Abstract
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Modification of surgical technique for ascending aortic atherosclerosis: impact on stroke reduction in coronary artery bypass grafting. Author(s): Hangler HB, Nagele G, Danzmayr M, Mueller L, Ruttmann E, Laufer G, Bonatti J. Source: The Journal of Thoracic and Cardiovascular Surgery. 2003 August; 126(2): 391400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928635&dopt=Abstract
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Modulating atherosclerosis through inhibition or blockade of angiotensin. Author(s): Rosenson RS. Source: Clin Cardiol. 2003 July; 26(7): 305-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862295&dopt=Abstract
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Modulation of PPARgamma activity with pharmaceutical agents: treatment of insulin resistance and atherosclerosis. Author(s): Wang M, Tafuri S. Source: Journal of Cellular Biochemistry. 2003 May 1; 89(1): 38-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682906&dopt=Abstract
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Molecular mimicry in atherosclerosis: a role for heat shock proteins in immunisation. Author(s): Lamb DJ, El-Sankary W, Ferns GA. Source: Atherosclerosis. 2003 April; 167(2): 177-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818399&dopt=Abstract
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Myeloperoxidase gene variation as a determinant of atherosclerosis progression in the abdominal and thoracic aorta: an autopsy study. Author(s): Makela R, Karhunen PJ, Kunnas TA, Ilveskoski E, Kajander OA, Mikkelsson J, Perola M, Penttila A, Lehtimaki T. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 July; 83(7): 919-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861032&dopt=Abstract
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New atherosclerosis risk factors in obese, hypertensive and diabetic children and adolescents. Author(s): Glowinska B, Urban M, Koput A, Galar M. Source: Atherosclerosis. 2003 April; 167(2): 275-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12818410&dopt=Abstract
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Nocturnal oxygen desaturation correlates with the severity of coronary atherosclerosis in coronary artery disease. Author(s): Hayashi M, Fujimoto K, Urushibata K, Uchikawa S, Imamura H, Kubo K. Source: Chest. 2003 September; 124(3): 936-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970020&dopt=Abstract
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Occupational physical activity in the atherosclerosis risk in communities study. Author(s): Evenson KR, Rosamond WD, Cai J, Pereira MA, Ainsworth BE. Source: Annals of Epidemiology. 2003 May; 13(5): 351-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821274&dopt=Abstract
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Plasma fatty acid composition and incidence of diabetes in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Author(s): Wang L, Folsom AR, Zheng ZJ, Pankow JS, Eckfeldt JH; ARIC Study Investigators. Source: The American Journal of Clinical Nutrition. 2003 July; 78(1): 91-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816776&dopt=Abstract
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Plasma vitronectin levels in patients with coronary atherosclerosis are increased and correlate with extent of disease. Author(s): Ekmekci H, Sonmez H, Ekmekci OB, Ozturk Z, Domanic N, Kokoglu E. Source: Journal of Thrombosis and Thrombolysis. 2002 December; 14(3): 221-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913402&dopt=Abstract
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Possible role of parathyroid hormone-related protein as a proinflammatory cytokine in atherosclerosis. Author(s): Martin-Ventura JL, Ortego M, Esbrit P, Hernandez-Presa MA, Ortega L, Egido J. Source: Stroke; a Journal of Cerebral Circulation. 2003 July; 34(7): 1783-9. Epub 2003 June 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805493&dopt=Abstract
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PPAR agonists in the treatment of atherosclerosis. Author(s): Francis GA, Annicotte JS, Auwerx J. Source: Current Opinion in Pharmacology. 2003 April; 3(2): 186-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12681242&dopt=Abstract
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Preclinical coronary atherosclerosis in a population with low incidence of myocardial infarction: cross sectional autopsy study. Author(s): Bertomeu A, Garcia-Vidal O, Farre X, Galobart A, Vazquez M, Laguna JC, Ros E. Source: Bmj (Clinical Research Ed.). 2003 September 13; 327(7415): 591-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969923&dopt=Abstract
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Prevalence of diabetes and/or ischaemic heart disease in classes of increasing carotid artery atherosclerosis: an ultrasonographic study. Author(s): Inchiostro S, Dalfollo M, Marzano A, Citroni N, Peccatori S, Fait D, De Venuto G. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2003 August; 20(8): 670-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873297&dopt=Abstract
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Prevalence of risk factors for coronary atherosclerosis in a cross-sectional population of Andhra Pradesh. Author(s): Reddy NK, Kumar DN, Rayudu NV, Sastry BK, Raju BS. Source: Indian Heart J. 2002 November-December; 54(6): 697-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674183&dopt=Abstract
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Pro12Ala of the peroxisome proliferator-activated receptor-gamma2 gene is associated with lower serum insulin levels in nonobese African Americans: the Atherosclerosis Risk in Communities Study. Author(s): Kao WH, Coresh J, Shuldiner AR, Boerwinkle E, Bray MS, Brancati FL; Atherosclerosis Risk in Communities Study. Source: Diabetes. 2003 June; 52(6): 1568-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765972&dopt=Abstract
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Promoter (4G/5G) plasminogen activator inhibitor-1 genotype and plasminogen activator inhibitor-1 levels in blacks, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study. Author(s): Festa A, D'Agostino R Jr, Rich SS, Jenny NS, Tracy RP, Haffner SM. Source: Circulation. 2003 May 20; 107(19): 2422-7. Epub 2003 April 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719278&dopt=Abstract
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Prospective association between hormone replacement therapy, heart rate, and heart rate variability. The Atherosclerosis risk in communities study. Author(s): Carnethon MR, Anthony MS, Cascio WE, Folsom AR, Rautaharju PM, Liao D, Evans GW, Heiss G. Source: Journal of Clinical Epidemiology. 2003 June; 56(6): 565-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873652&dopt=Abstract
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Prospective investigation of autonomic nervous system function and the development of type 2 diabetes: the Atherosclerosis Risk In Communities study, 1987-1998. Author(s): Carnethon MR, Golden SH, Folsom AR, Haskell W, Liao D. Source: Circulation. 2003 May 6; 107(17): 2190-5. Epub 2003 April 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695289&dopt=Abstract
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Quantitative assessment of mild-to-moderate coronary atherosclerosis by computerized border detection in 3D IVUS. Author(s): von Birgelen C. Source: The International Journal of Cardiovascular Imaging. 2003 April; 19(2): 105-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749390&dopt=Abstract
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Racial disparity in long-term mortality rate after hospitalization for myocardial infarction: the Atherosclerosis Risk in Communities study. Author(s): Ding J, Diez Roux AV, Nieto FJ, McNamara RL, Hetmanski JB, Taylor HA Jr, Tyroler HA. Source: American Heart Journal. 2003 September; 146(3): 459-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947363&dopt=Abstract
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Randomized controlled trial evidence that estrogen replacement therapy reduces the progression of subclinical atherosclerosis in healthy postmenopausal women without preexisting cardiovascular disease. Author(s): Hodis HN, Mack WJ, Lobo RA. Source: Circulation. 2003 July 8; 108(1): E5; Author Reply E5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847059&dopt=Abstract
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Re: “Serum insulin and glucose levels and breast cancer incidence: the Atherosclerosis Risk in Communities Study”. Author(s): Muti P. Source: American Journal of Epidemiology. 2003 September 15; 158(6): 607; Author Reply 608. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12965886&dopt=Abstract
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Relationship between periodontal disease and C-reactive protein among adults in the Atherosclerosis Risk in Communities study. Author(s): Slade GD, Ghezzi EM, Heiss G, Beck JD, Riche E, Offenbacher S. Source: Archives of Internal Medicine. 2003 May 26; 163(10): 1172-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767953&dopt=Abstract
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Relationships among apolipoprotein A1 gene polymorphisms, lipid levels and coronary atherosclerosis disease. Author(s): Zou Y, Hu D, Yang X, Jia X, Wang L, Cui L, Liu X, Gao M, Wei Y, Xu Z. Source: Chinese Medical Journal. 2003 May; 116(5): 665-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875674&dopt=Abstract
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Relationships between low-density lipoprotein particle size, plasma lipoproteins, and progression of coronary artery disease: the Diabetes Atherosclerosis Intervention Study (DAIS). Author(s): Vakkilainen J, Steiner G, Ansquer JC, Aubin F, Rattier S, Foucher C, Hamsten A, Taskinen MR; DAIS Group. Source: Circulation. 2003 April 8; 107(13): 1733-7. Epub 2003 March 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665498&dopt=Abstract
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Reliability of nested PCR for the detection of Chlamydia pneumoniae in carotid artery atherosclerosis. Author(s): Apfalter P, Hammerschlag MR, Boman J. Source: Stroke; a Journal of Cerebral Circulation. 2003 July; 34(7): E73-5; Author Reply E73-5. Epub 2003 June 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12817098&dopt=Abstract
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Risk factors for asymptomatic atherosclerosis in Japanese type 2 diabetic patients without diabetic microvascular complications. Author(s): Goya K, Kitamura T, Inaba M, Otsuki M, Yamamoto H, Kurebayashi S, Sumitani S, Saito H, Kouhara H, Kasayama S, Kawase I. Source: Metabolism: Clinical and Experimental. 2003 October; 52(10): 1302-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14564682&dopt=Abstract
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Risk factors for progression of atherosclerosis measured at multiple sites in the arterial tree: the Rotterdam Study. Author(s): van der Meer IM, Iglesias del Sol A, Hak AE, Bots ML, Hofman A, Witteman JC. Source: Stroke; a Journal of Cerebral Circulation. 2003 October; 34(10): 2374-9. Epub 2003 August 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947155&dopt=Abstract
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Risk of atherosclerosis: interaction of smoking and glutathione S-transferase genes. Author(s): Olshan AF, Li R, Pankow JS, Bray M, Tyroler HA, Chambless LE, Boerwinkle E, Pittman GS, Bell DA. Source: Epidemiology (Cambridge, Mass.). 2003 May; 14(3): 321-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12859033&dopt=Abstract
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Role of Chlamydia pneumoniae-infected macrophages in atherosclerosis developments of the carotid artery. Author(s): Kuroda S, Kobayashi T, Ishii N, Ikeda J, Shinohe Y, Houkin K, Iwasaki Y, Nagashima K. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2003 March; 23(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12722920&dopt=Abstract
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Screening for asymptomatic internal carotid artery stenosis and aneurysm of the abdominal aorta: comparing the yield between patients with manifest atherosclerosis and patients with risk factors for atherosclerosis only. Author(s): Kurvers HA, van der Graaf Y, Blankensteijn JD, Visseren FL, Eikelboom BC; SMART Study Group. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 June; 37(6): 1226-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764269&dopt=Abstract
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SLE - Practical and theoretical barriers to the prevention of accelerated atherosclerosis in systemic lupus erythematosus. Author(s): Costenbader KH, Liang MH. Source: Arthritis Research & Therapy. 2003; 5(4): 178-9. Epub 2003 May 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823848&dopt=Abstract
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Smoking induced burn, accelerated atherosclerosis and electrical burn. Author(s): Dwivedi S, Agarwal MP, Gangwal P. Source: Indian Journal of Medical Sciences. 2002 October; 56(10): 535. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12712767&dopt=Abstract
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Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation. Author(s): Caplice NM, Bunch TJ, Stalboerger PG, Wang S, Simper D, Miller DV, Russell SJ, Litzow MR, Edwards WD. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 April 15; 100(8): 4754-9. Epub 2003 March 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665618&dopt=Abstract
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Soluble integrin adhesion receptors and atherosclerosis: much heat and a little light? Author(s): Hillis GS. Source: Journal of Human Hypertension. 2003 July; 17(7): 449-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821950&dopt=Abstract
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Surrogate markers of atherosclerosis: impact of statins. Author(s): Kastelein JJ, Wiegman A, de Groot E. Source: Atherosclerosis. Supplements. 2003 March; 4(1): 31-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714035&dopt=Abstract
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TDAG51 is induced by homocysteine, promotes detachment-mediated programmed cell death, and contributes to the cevelopment of atherosclerosis in hyperhomocysteinemia. Author(s): Hossain GS, van Thienen JV, Werstuck GH, Zhou J, Sood SK, Dickhout JG, de Koning AB, Tang D, Wu D, Falk E, Poddar R, Jacobsen DW, Zhang K, Kaufman RJ, Austin RC. Source: The Journal of Biological Chemistry. 2003 August 8; 278(32): 30317-27. Epub 2003 May 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738777&dopt=Abstract
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The association of antibodies against oxidized low-density lipoprotein with atherosclerosis in hemodialysis patients. Author(s): Shoji T, Kimoto E, Shinohara K, Emoto M, Ishimura E, Miki T, Tsujimoto Y, Tabata T, Nishizawa Y. Source: Kidney International. Supplement. 2003 May; (84): S128-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694327&dopt=Abstract
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The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis. Author(s): Heeneman S, Cleutjens JP, Faber BC, Creemers EE, van Suylen RJ, Lutgens E, Cleutjens KB, Daemen MJ. Source: The Journal of Pathology. 2003 July; 200(4): 516-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12845619&dopt=Abstract
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The effects of tobacco smoke on the homocysteine level--a risk factor of atherosclerosis. Author(s): Sobczak AJ. Source: Addiction Biology. 2003 June; 8(2): 147-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850773&dopt=Abstract
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The importance of reaching lipid targets: statins and the prevention of atherosclerosis. Author(s): Schwandt P. Source: Int J Clin Pract. 2003 June; 57(5): 396-404. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846345&dopt=Abstract
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The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type II diabetes and metabolic syndrome X. Author(s): Black PH. Source: Brain, Behavior, and Immunity. 2003 October; 17(5): 350-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946657&dopt=Abstract
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The interaction between MTHFR 677 C-->T genotype and folate status is a determinant of coronary atherosclerosis risk. Author(s): Girelli D, Martinelli N, Pizzolo F, Friso S, Olivieri O, Stranieri C, Trabetti E, Faccini G, Tinazzi E, Pignatti PF, Corrocher R. Source: The Journal of Nutrition. 2003 May; 133(5): 1281-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12730410&dopt=Abstract
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The Jeremiah Metzger Lecture. Pathogenesis of atherosclerosis: redox as a unifying mechanism. Author(s): Alexander RW. Source: Trans Am Clin Climatol Assoc. 2003; 114: 273-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813926&dopt=Abstract
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The metabolic syndrome, diabetes, and subclinical atherosclerosis assessed by coronary calcium. Author(s): Wong ND, Sciammarella MG, Polk D, Gallagher A, Miranda-Peats L, Whitcomb B, Hachamovitch R, Friedman JD, Hayes S, Berman DS. Source: Journal of the American College of Cardiology. 2003 May 7; 41(9): 1547-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742296&dopt=Abstract
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The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complications in type 2 diabetes. Author(s): Dandona P, Aljada A, Chaudhuri A, Bandyopadhyay A. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 June; 88(6): 2422-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788837&dopt=Abstract
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The potential role of peroxisome proliferator-activated receptors on inflammation in type 2 diabetes mellitus and atherosclerosis. Author(s): Plutzky J. Source: The American Journal of Cardiology. 2003 August 18; 92(4A): 34J-41J. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12957325&dopt=Abstract
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The relationship between leptin and lipids in atherosclerosis. Author(s): Tamer L, Ercan B, Unlu A, Sucu N, Pekdemir H, Eskandari G, Atik U. Source: Indian Heart J. 2002 November-December; 54(6): 692-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674182&dopt=Abstract
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The role of inflammation in atherosclerosis. Author(s): DeGraba TJ. Source: Adv Neurol. 2003; 92: 29-42. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760164&dopt=Abstract
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The use of digital imaging technology to assess the pathogenesis of coronary atherosclerosis: the role of elastin. Author(s): Mohamed A, Benghuzzi H. Source: Biomed Sci Instrum. 2003; 39: 428-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724931&dopt=Abstract
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Total body MR angiography and atherosclerosis. Author(s): Merlino B, Salcuni M, Salute L, Marano R, Bonomo L. Source: Rays. 2001 October-December; 26(4): 305-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696284&dopt=Abstract
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Treatment of atherosclerosis in the new millennium: is there a role for vitamin E? Author(s): Meagher EA. Source: Preventive Cardiology. 2003 Spring; 6(2): 85-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732794&dopt=Abstract
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Treatment of patients with combined coronary and carotid atherosclerosis. Author(s): Ricotta JJ, Wall LP. Source: The Journal of Cardiovascular Surgery. 2003 June; 44(3): 363-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832989&dopt=Abstract
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Update on imaging aortic atherosclerosis. Author(s): Amarenco P, Cohen A. Source: Adv Neurol. 2003; 92: 75-89. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760169&dopt=Abstract
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CHAPTER 2. NUTRITION AND ATHEROSCLEROSIS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and atherosclerosis.
Finding Nutrition Studies on Atherosclerosis 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 “atherosclerosis” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on atherosclerosis: •
A risk factor for atherosclerosis: triglyceride-rich lipoproteins. Author(s): Cardiovascular Research Institute, Pediatric Lipid Clinic, University of California, San Francisco, USA. Source: Malloy, M J Kane, J P Adv-Intern-Med. 2001; 47: 111-36 0065-2822
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A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study. Author(s): Papworth Hospital, Cambridge, UK. Source: Clarke, S C Kelleher, J Lloyd Jones, H Slack, M Schofiel, P M BJOG. 2002 September; 109(9): 1056-62 1470-0328
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Aggressive LDL-cholesterol lowering with atorvastatin results in regression of atherosclerosis. Source: Anonymous Cardiovasc-J-S-Afr. 2001 Feb-March; 12(1): 56 1015-9657
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Anti-beta 2-glycoprotein I autoantibodies and atherosclerosis. Author(s): Department of Cell Chemistry, Department of Medicine III, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 7008558, Japan.
[email protected] Source: Matsuura, E Kobayashi, K Kasahara, J Yasuda, T Makino, H Koike, T Shoenfeld, Y Int-Rev-Immunol. 2002 Jan-February; 21(1): 51-66 0883-0185
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Antioxidant therapy and atherosclerosis: animal and human studies. Author(s): Department of Medicine, Center for Experimental Therapeutics, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
[email protected] Source: Meagher, E Rader, D J Trends-Cardiovasc-Med. 2001 Apr-May; 11(3-4): 162-5 1050-1738
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Anti-oxidants and atherosclerosis. Author(s): Universite de Lille 1 (France). Centre Clinico Biologique des Lipides Source: Lecerf, J.M. Luc, G. Fruchart, J.C. Medecine-et-Nutrition (France). (1996). volume 32(1) page 8-16. 0398-7604
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Apheresis technology for prevention and regression of atherosclerosis. Author(s): National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
[email protected] Source: Yamamoto, A Harada Shiba, M Kawaguchi, A Tsushima, M Ther-Apher. 2001 August; 5(4): 221-5 1091-6660
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Association between behavior-dependent cardiovascular risk factors and asymptomatic carotid atherosclerosis in a general population. Author(s): Institute of Epidemiology and Social Medicine, Department of Neurology, Ernst-Moritz-Arndt University of Greifswald, Germany. Source: Luedemann, J Schminke, U Berger, K Piek, M Willich, S N Doring, A John, U Kessler, C Stroke. 2002 December; 33(12): 2929-35 1524-4628
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Changes in heat shock protein 70 localization and its content in rabbit aorta at various stages of experimental atherosclerosis. Author(s): Department of Biophysics, Panjab University, Chandigarh 160014, India. Source: Geetanjali, Bansal Uma, Singh Bansal, M P Cardiovasc-Pathol. 2002 Mar-April; 11(2): 97-103 1054-8807
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Chemiluminescence assay of the antioxidant state in patients with atherosclerosis. Author(s): Institute of Physicochemical Medicine, Russian Ministry of Health, Moscow.
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Source: Azizova, O A Piryazev, A P Sherstnev, M P Drinitsina, S V Lopukhin, Y M BullExp-Biol-Med. 2001 May; 131(5): 444-5 0007-4888 •
Chlamydia pneumoniae and atherosclerosis -- what we know and what we don't. Author(s): Whipps Cross University Hospital, Leytonstone, London E11 1NR, UK. Source: Ngeh, J Anand, V Gupta, S Clin-Microbiol-Infect. 2002 January; 8(1): 2-13 1198743X
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Class A scavenger receptors, macrophages, and atherosclerosis. Author(s): Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
[email protected] Source: Linton, M F Fazio, S Curr-Opin-Lipidol. 2001 October; 12(5): 489-95 0957-9672
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Clinical carotid atherosclerosis. Author(s): Department of Radiology, Division of Neuroradiology, Johns Hopkins University School of Medicine, Phipps B-100, 600 North Wolfe Street, Baltimore, MD 21287-2182, USA.
[email protected] Source: Wasserman, B A Neuroimaging-Clin-N-Am. 2002 August; 12(3): 403-19 10525149
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Comparative effects of ACE inhibitors and an angiotensin receptor blocker on atherosclerosis and vascular function. Author(s): Division of Cardiology, Department of Medicine, University of California, San Francisco 94143, USA. Source: Sun, Y P Zhu, B Q Browne, A E Pulukurthy, S Chou, T M Sudhir, K Glantz, S A Deedwania, P C Chatterjee, K Parmley, W W J-Cardiovasc-Pharmacol-Ther. 2001 April; 6(2): 175-81 1074-2484
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Comparison of tibolone and conjugated equine estrogens effects on carotid artery atherosclerosis of postmenopausal monkeys. Author(s): Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA.
[email protected] Source: Clarkson, T B Anthony, M S Mikkola, T S St Clair, R W Stroke. 2002 November; 33(11): 2700-3 1524-4628
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Cytoplasmic fatty acid-binding proteins: emerging roles in metabolism and atherosclerosis. Author(s): Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6300, USA. Source: Boord, Jeffrey B Fazio, Sergio Linton, MacRae F Curr-Opin-Lipidol. 2002 April; 13(2): 141-7 0957-9672
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Detection of atherosclerosis using a novel positron-sensitive probe and 18fluorodeoxyglucose (FDG). Author(s): Department of Medicine, University of Michigan Health System, Ann Arbor, USA.
[email protected] Source: Lederman, R J Raylman, R R Fisher, S J Kison, P V San, H Nabel, E G Wahl, R L Nucl-Med-Commun. 2001 July; 22(7): 747-53 0143-3636
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Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats. Author(s): Division of Pediatric Radiology, Lucile Salter Packard Children's Hospital, Stanford, California, USA.
[email protected] Source: Blankenberg, F G Wen, P Dai, M Zhu, D Panchal, S N Tait, J F Post, A M Strauss, H W Valantine, H A Pediatr-Radiol. 2001 December; 31(12): 827-35 0301-0449
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Development of atherosclerosis in osteopontin transgenic mice. Author(s): Department of Cardiovascular Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Source: Chiba, S Okamoto, H Kon, S Kimura, C Murakami, M Inobe, M Matsui, Y Sugawara, T Shimizu, T Uede, T Kitabatake, A Heart-Vessels. 2002 March; 16(3): 111-7 0910-8327
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Dietary phytoestrogens and estrogen inhibit experimental atherosclerosis. Author(s): Center for Clinical and Basic Research, Ballerup Byvej 222, DK-2750 Ballerup, Denmark. Source: Alexandersen, P Haarbo, J Breinholt, V Christiansen, C Climacteric. 2001 June; 4(2): 151-9 1369-7137
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Do soy isoflavones lower cholesterol, inhibit atherosclerosis, and play a role in cancer prevention? Author(s): Department of Biological Sciences, Kingsborough Community College, City University of New York, Brooklyn, New York, USA. Source: Arliss, R M Biermann, C A Holist-Nurs-Pract. 2002 October; 16(5): 40-8 08879311
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Early feeding and atherosclerosis. Source: Mott, G.E. Long-term consequences of early feeding /. Philadelphia : LippincottRaven, c1996. page 113-122. ISBN: 0397517289
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Editorial Comment: MMP inhibition and the development of cerebrovascular atherosclerosis: The road ahead. Source: Napoli, C Stroke. 2002 December; 33(12): 2865 1524-4628
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Endothelin A receptor antagonist LU 135252 inhibits hypercholesterolemia-induced, but not deendothelialization-induced, atherosclerosis in rabbit arteries. Author(s): Department of Diagnostic Radiology, University of Tubingen, Germany.
[email protected] Source: Tepe, Gunnar Brehme, Ute Seeger, Harald Raschack, Manfred Claussen, Claus D Duda, Stephan H Invest-Radiol. 2002 June; 37(6): 349-55 0020-9996
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Environmental modulation of atherosclerosis end points in familial hypercholesterolemia. Author(s): Blackburn Cardiovascular Genetics Laboratory, John P. Robarts Research Institute, University of Western Ontario, 406-100 Perth Drive, London, ON, Canada N6A 5K8.
[email protected] Source: Hegele, Robert A Atheroscler-Suppl. 2002 March; 2(3): 5-7 1567-5688
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Estrogen and atherosclerosis. Author(s): Franz-Volhard-Klinik, Humboldt University of Berlin, Wiltbergstrasse 50, 13125 Berlin-Buch, Germany.
[email protected] Source: Luft, Friedrich C J-Mol-Med. 2002 March; 80(3): 133-4 0946-2716
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Evidence for grape, wine and tea polyphenols as modulators of atherosclerosis and ischemic heart disease in humans. Source: Dubick, M.A. Omaye, S.T. J-nutraceuticals-funct-med-foods. Binghamton, NY : Pharmaceutical Products Press, an imprint of the Haworth Press, Inc., c1997-. 2001. volume 3 (3) page 67-93. 1089-4179
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Genetic determinants of homocysteine thiolactonase activity in humans: implications for atherosclerosis. Author(s): Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
[email protected] Source: Jakubowski, H Ambrosius, W T Pratt, J H FEBS-Lett. 2001 Feb 23; 491(1-2): 35-9 0014-5793
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Genetic loci determining bone density in mice with diet-induced atherosclerosis. Author(s): Departments of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095, USA.
[email protected] Source: Drake, T A Schadt, E Hannani, K Kabo, J M Krass, K Colinayo, V Greaser , L E 3rd Goldin, J Lusis, A J Physiol-Genomics. 2001 April 27; 5(4): 205-15 1094-8341
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Heat-shock proteins and atherosclerosis. Author(s): Immunoallergology Unit-Hospital Santa Maria-1699 Lisbon, Portugal. Source: Ferreira, M Branco Carlos, A G Palma Allerg-Immunol-(Paris). 2002 June; 34(6): 204-7 0397-9148
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Imaging of the endothelial dysfunction in coronary atherosclerosis. Author(s): Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and Niuvanniemi Hospital, Finland.
[email protected] Source: Kuikka, J T Raitakari, O T Gould, K L Eur-J-Nucl-Med. 2001 October; 28(10): 1567-78 0340-6997
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Impact of saturated and trans fatty acid enriched oil blends on atherosclerosis in rabbits fed cholesterol-free diets. Author(s): Palm Oil Research Institute of Malaysia (PORIM), Kuala Lumpur (Malaysia) Source: Sundram, K. Pathmanathan, R. Wong, K.T. Baskaran, G. Asia-Pacific-Journal-ofClinical-Nutrition (United Kingdom). (1997). volume 6(1) page 31-35.
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Inflammatory mechanisms in atherosclerosis: from laboratory evidence to clinical application. Author(s): Center for Cardiovascular Disease Prevention, Department of Medicine, Brigham and Women's Hospital, Havard Medical School, Boston, MA 02215, USA. Source: Blake, G J Ridker, P M Ital-Heart-J. 2001 November; 2(11): 796-800 1129-471X
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Interaction of the common apolipoprotein C-III (APOC3 -482C > T) and hepatic lipase (LIPC -514C > T) promoter variants affects glucose tolerance in young adults. European Atherosclerosis Research Study II (EARS-II). Author(s): Department of Internal Medicien, Erasmus University, Rotterdam, The Netherlands.
[email protected] Source: Jansen, H Waterworth, D M Nicaud, V Ehnholm, C Talmud, P J Ann-HumGenet. 2001 May; 65(Pt 3): 237-43 0003-4800
•
Lipid peroxidation in mouse models of atherosclerosis. Author(s): Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
[email protected] Source: Pratico, D Trends-Cardiovasc-Med. 2001 Apr-May; 11(3-4): 112-6 1050-1738
•
Lipids and atherosclerosis: clinical management of hypercholesterolaemia. Author(s): Alfred and Baker Medical Unit, Baker Medical Research Institute and Heart Centre, Alfred Hospital, Commercial Rd, Prahran 3181, Australia.
[email protected] Source: Chin Dusting, J P Shaw, J A Expert-Opin-Pharmacother. 2001 March; 2(3): 419-30 1465-6566
112 Atherosclerosis
•
Lycopene, atherosclerosis, and coronary heart disease. Author(s): Research Institute of Public Health, University of Kuopio, Kuopio, Finland 70211.
[email protected] Source: Rissanen, T Voutilainen, S Nyyssonen, K Salonen, J T Exp-Biol-Med-(Maywood). 2002 November; 227(10): 900-7 1535-3702
•
Macrophage scavenger receptor (SR-A I/II) deficiency reduced diet-induced atherosclerosis in C57BL/6J mice. Author(s): Pharmaceutical Technology Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan. Source: Kamada, N Kodama, T Suzuki, H J-Atheroscler-Thromb. 2001; 8(1): 1-6 13403478
•
Mapping of microsatellite loci and association of aorta atherosclerosis with LG VI markers in the rabbit. Author(s): Department of Laboratory Animal Science, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, The Netherlands.
[email protected] Source: Korstanje, R Gillissen, G F Kodde, L P Den Bieman, M Lankhorst, A Van Zutphen, L F Van Lith, H A Physiol-Genomics. 2001 June 6; 6(1): 11-8 1094-8341
•
Mechanisms for oxidizing low-density lipoprotein. Insights from patterns of oxidation products in the artery wall and from mouse models of atherosclerosis. Author(s): Department of Medicine, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, USA. Source: Gaut, J P Heinecke, J W Trends-Cardiovasc-Med. 2001 Apr-May; 11(3-4): 103-12 1050-1738
•
Miscellaneous medications for the management of atherosclerosis: mayhem or miracle? Author(s): Mote Vascular Foundation, Sarasota, FL, USA. Source: Samson, R H Semin-Vasc-Surg. 2002 December; 15(4): 275-87 0895-7967
•
Non-invasive vascular detection of early signs of atherosclerosis in hypercholesterolemic children: why and how. Author(s): Dipartimento di Medicina Clinica e Sperimentale, Universita Federico II, Via S. Pansini 5, 80131 Napoli, Italy. Source: Rubba, P Iannuzzi, A Faccenda, F De Leo, F Pauciullo, P Nutr-MetabCardiovasc-Dis. 2001 October; 11 Suppl 5: 10-5 0939-4753
•
Oxidants and antioxidants in atherosclerosis. Author(s): Biochemistry Group, The Heart Research Institute, Sydney, Australia. Source: Mashima, R Witting, P K Stocker, R Curr-Opin-Lipidol. 2001 August; 12(4): 4118 0957-9672
•
Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols. Author(s): Departments of Biomedical Engineering and Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA. Source: Colles, S M Maxson, J M Carlson, S G Chisolm, G M Trends-Cardiovasc-Med. 2001 Apr-May; 11(3-4): 131-8 1050-1738
•
Paradoxical effects of vitamin E: oxidized lipoproteins, prostanoids and the pathogenesis of atherosclerosis. Source: Cornwell, D.G. Zhang, H. Davis, W.B. Whisler, R.L. Panganamala, R.V. NATOASI-ser,-Ser-A,-Life-sci. New York : Plenum, 1984-. 1990. volume 189 page 215-237. 02581213
Nutrition
113
•
Pentosidine, carotid atherosclerosis and alterations in left ventricular geometry in hemodialysis patients. Author(s): CNR, Centre of Clinical Physiology and Division of Nephrology, Reggio Calabria, Italy.
[email protected] Source: Zoccali, C Mallamaci, F Asahia, K Benedetto, F A Tripepi, G Tripepi, R Nicocia, G Buemi, M Miyata, T J-Nephrol. 2001 Jul-August; 14(4): 293-8 1120-3625
•
Pharmaceutical initiatives to combat atherosclerosis--what to do with the good, the bad, and the ugly lipoproteins. Author(s): Mote Vascular Foundation, Sarasota, FL, USA. Source: Samson, R H Semin-Vasc-Surg. 2002 December; 15(4): 204-15 0895-7967
•
Plasma homocysteine levels and atherosclerosis in Japan: epidemiological study by use of carotid ultrasonography. Author(s): Third Department of Internal Medicine and Cardiovascular Research Institute, Kurume University School of Medicine, Kurume, Japan.
[email protected] Source: Adachi, H Hirai, Y Fujiura, Y Matsuoka, H Satoh, A Imaizumi, T Stroke. 2002 September; 33(9): 2177-81 1524-4628
•
Platelet labelling in atherosclerosis. Source: Sinzinger, H. Virgolini, I. Fitscha, P. NATO-ASI-ser,-Ser-A,-Life-sci. New York : Plenum, 1984-. 1991. volume 219 page 181-188. 0258-1213
•
Protective effects of Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) against atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Author(s): Kampo & Pharmacognosy Laboratory, Tsumura & Co., Yoshiwara, Inashikigun, Ibaraki, 3586 Ami-machi, 300-1192 Japan.
[email protected] Source: Yoshie, F Iizuka, A Kubo, M Komatsu, Y Matsumoto, A Itakura, H Takeda, H Matsumiya, T Kondo, K Pharmacol-Res. 2001 May; 43(5): 481-8 1043-6618
•
Relevance of hypercholesterolemia to fetal and pediatric atherosclerosis. Author(s): Department of Pathology and Molecular Medicine, Wellington School of Medicine, New Zealand.
[email protected] Source: Stehbens, W E Pediatr-Pathol-Mol-Med. 2002 May-June; 21(3): 259-78 1522-7952
•
Role of 12-lipoxygenase and oxidant stress in hyperglycaemia-induced acceleration of atherosclerosis in a diabetic pig model. Author(s): Gonda Diabetes Center, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
[email protected] Source: NataraJanuary, R Gerrity, R G Gu, J L Lanting, L Thomas, L Nadler, J L Diabetologia. 2002 Jan; 45(1): 125-33 0012-186X
•
Studies of apoptosis and bcl-2 in experimental atherosclerosis in rabbit and influence of selenium supplementation. Author(s): Department of Biophysics, Panjab University, Chandigarh, India. Source: Mehta, U Kang, B P Bansal, G Bansal, M P Gen-Physiol-Biophys. 2002 March; 21(1): 15-29 0231-5882
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The effect of antioxidant-containing fraction from fermented soybean food on atherosclerosis development in cholesterol-fed rabbits. Source: Yokota, T. Hattori, T. Ohishi, H. Hasegawa, K. Watanabe, K. Lebensm-WissTechnol. London : Academic Press. 1996. volume 29 (8) page 751-755. 0023-6438
114 Atherosclerosis
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The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterollowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis. Author(s): Department of Medicine 0682, University of California San Diego, La Jolla, California 92093-0682, USA.
[email protected] Source: Palinski, W Napoli, C FASEB-J. 2002 September; 16(11): 1348-60 1530-6860
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The oxidative modification hypothesis of atherosclerosis: does it hold for humans? Author(s): Department of Medicine, Division of Endocrinology and Metabolism, Specialized Center of Research in Molecular Medicine and Atherosclerosis, University of California, San Diego School of Medicine, La Jolla, California, USA.
[email protected] Source: Witztum, J L Steinberg, D Trends-Cardiovasc-Med. 2001 Apr-May; 11(3-4): 93102 1050-1738
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The total peroxyl radical trapping potential in serum - an assay to define the stage of atherosclerosis. Author(s): Nicolae Simionescu Institute of Cellular Biology and Pathology, Bucharest, Romania. Source: Niculescu, L Stancu, C Sima, A Toporan, D Simionescu, M J-Cell-Mol-Med. 2001 Jul-September; 5(3): 285-94 1582-1838
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The use of radiolabeled low density lipoprotein for evaluating atherosclerosis: present status and future promise. Source: Kay, R. NATO-ASI-ser,-Ser-A,-Life-sci. New York : Plenum, 1984-. 1991. volume 219 page 171-179. 0258-1213
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True deficiency of antioxidant vitamins E and A in dialysis patients. Relationship with clinical patterns of atherosclerosis. Author(s): Servicio de Nefrologia, Hospitales Universitarios La Paz, Spain. Source: Aguilera, A Bajo, M A del Peso, G Diez, J J Codoceo, R Rebollo, F Mariano, M Selgas, R Adv-Perit-Dial. 2002; 18: 206-11 1197-8554
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Vervet monkeys and whole-food diets for studying the effects of dietary lipids on plasma lipoprotein metabolism and atherosclerosis. Author(s): National Research Programme for Nutritional Intervention Medical Research Council, Tygerberg (South Africa) Source: Benade, A.J.S. Fincham, J.E. Smuts, C.M. Weight, M.J. Jaarsveld, P.J. van Kruger, M. Asia-Pacific-Journal-of-Clinical-Nutrition (United Kingdom). (1997). volume 6(1) page 17-21.
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Vitamin E, atherosclerosis and thrombosis. Author(s): Institute of Clinical Medicine I, University La Sapienza, Rome, Italy.
[email protected] Source: Violi, F Micheletta, F Iuliano, L Thromb-Haemost. 2001 May; 85(5): 766-70 03406245
The following information is typical of that found when using the “Full IBIDS Database” to search for “atherosclerosis” (or a synonym): •
A risk factor for atherosclerosis: triglyceride-rich lipoproteins. Author(s): Cardiovascular Research Institute, Pediatric Lipid Clinic, University of California, San Francisco, USA. Source: Malloy, M J Kane, J P Adv-Intern-Med. 2001; 47: 111-36 0065-2822
Nutrition
115
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A study of hormone replacement therapy in postmenopausal women with ischaemic heart disease: the Papworth HRT atherosclerosis study. Author(s): Papworth Hospital, Cambridge, UK. Source: Clarke, S C Kelleher, J Lloyd Jones, H Slack, M Schofiel, P M BJOG. 2002 September; 109(9): 1056-62 1470-0328
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Aggressive LDL-cholesterol lowering with atorvastatin results in regression of atherosclerosis. Source: Anonymous Cardiovasc-J-S-Afr. 2001 Feb-March; 12(1): 56 1015-9657
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Anti-beta 2-glycoprotein I autoantibodies and atherosclerosis. Author(s): Department of Cell Chemistry, Department of Medicine III, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 7008558, Japan.
[email protected] Source: Matsuura, E Kobayashi, K Kasahara, J Yasuda, T Makino, H Koike, T Shoenfeld, Y Int-Rev-Immunol. 2002 Jan-February; 21(1): 51-66 0883-0185
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Antioxidant therapy and atherosclerosis: animal and human studies. Author(s): Department of Medicine, Center for Experimental Therapeutics, University of Pennsylvania Health System, Philadelphia, Pennsylvania, USA.
[email protected] Source: Meagher, E Rader, D J Trends-Cardiovasc-Med. 2001 Apr-May; 11(3-4): 162-5 1050-1738
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Anti-oxidants and atherosclerosis. Author(s): Universite de Lille 1 (France). Centre Clinico Biologique des Lipides Source: Lecerf, J.M. Luc, G. Fruchart, J.C. Medecine-et-Nutrition (France). (1996). volume 32(1) page 8-16. 0398-7604
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Apheresis technology for prevention and regression of atherosclerosis. Author(s): National Cardiovascular Center Research Institute, Suita, Osaka, Japan.
[email protected] Source: Yamamoto, A Harada Shiba, M Kawaguchi, A Tsushima, M Ther-Apher. 2001 August; 5(4): 221-5 1091-6660
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Association between behavior-dependent cardiovascular risk factors and asymptomatic carotid atherosclerosis in a general population. Author(s): Institute of Epidemiology and Social Medicine, Department of Neurology, Ernst-Moritz-Arndt University of Greifswald, Germany. Source: Luedemann, J Schminke, U Berger, K Piek, M Willich, S N Doring, A John, U Kessler, C Stroke. 2002 December; 33(12): 2929-35 1524-4628
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Changes in heat shock protein 70 localization and its content in rabbit aorta at various stages of experimental atherosclerosis. Author(s): Department of Biophysics, Panjab University, Chandigarh 160014, India. Source: Geetanjali, Bansal Uma, Singh Bansal, M P Cardiovasc-Pathol. 2002 Mar-April; 11(2): 97-103 1054-8807
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Chemiluminescence assay of the antioxidant state in patients with atherosclerosis. Author(s): Institute of Physicochemical Medicine, Russian Ministry of Health, Moscow. Source: Azizova, O A Piryazev, A P Sherstnev, M P Drinitsina, S V Lopukhin, Y M BullExp-Biol-Med. 2001 May; 131(5): 444-5 0007-4888
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Chlamydia pneumoniae and atherosclerosis -- what we know and what we don't. Author(s): Whipps Cross University Hospital, Leytonstone, London E11 1NR, UK. Source: Ngeh, J Anand, V Gupta, S Clin-Microbiol-Infect. 2002 January; 8(1): 2-13 1198743X
116 Atherosclerosis
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Class A scavenger receptors, macrophages, and atherosclerosis. Author(s): Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
[email protected] Source: Linton, M F Fazio, S Curr-Opin-Lipidol. 2001 October; 12(5): 489-95 0957-9672
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Clinical carotid atherosclerosis. Author(s): Department of Radiology, Division of Neuroradiology, Johns Hopkins University School of Medicine, Phipps B-100, 600 North Wolfe Street, Baltimore, MD 21287-2182, USA.
[email protected] Source: Wasserman, B A Neuroimaging-Clin-N-Am. 2002 August; 12(3): 403-19 10525149
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Comparative effects of ACE inhibitors and an angiotensin receptor blocker on atherosclerosis and vascular function. Author(s): Division of Cardiology, Department of Medicine, University of California, San Francisco 94143, USA. Source: Sun, Y P Zhu, B Q Browne, A E Pulukurthy, S Chou, T M Sudhir, K Glantz, S A Deedwania, P C Chatterjee, K Parmley, W W J-Cardiovasc-Pharmacol-Ther. 2001 April; 6(2): 175-81 1074-2484
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Comparison of tibolone and conjugated equine estrogens effects on carotid artery atherosclerosis of postmenopausal monkeys. Author(s): Comparative Medicine Clinical Research Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1040, USA.
[email protected] Source: Clarkson, T B Anthony, M S Mikkola, T S St Clair, R W Stroke. 2002 November; 33(11): 2700-3 1524-4628
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Cytoplasmic fatty acid-binding proteins: emerging roles in metabolism and atherosclerosis. Author(s): Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6300, USA. Source: Boord, Jeffrey B Fazio, Sergio Linton, MacRae F Curr-Opin-Lipidol. 2002 April; 13(2): 141-7 0957-9672
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Detection of atherosclerosis using a novel positron-sensitive probe and 18fluorodeoxyglucose (FDG). Author(s): Department of Medicine, University of Michigan Health System, Ann Arbor, USA.
[email protected] Source: Lederman, R J Raylman, R R Fisher, S J Kison, P V San, H Nabel, E G Wahl, R L Nucl-Med-Commun. 2001 July; 22(7): 747-53 0143-3636
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Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats. Author(s): Division of Pediatric Radiology, Lucile Salter Packard Children's Hospital, Stanford, California, USA.
[email protected] Source: Blankenberg, F G Wen, P Dai, M Zhu, D Panchal, S N Tait, J F Post, A M Strauss, H W Valantine, H A Pediatr-Radiol. 2001 December; 31(12): 827-35 0301-0449
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Development of atherosclerosis in osteopontin transgenic mice. Author(s): Department of Cardiovascular Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Source: Chiba, S Okamoto, H Kon, S Kimura, C Murakami, M Inobe, M Matsui, Y Sugawara, T Shimizu, T Uede, T Kitabatake, A Heart-Vessels. 2002 March; 16(3): 111-7 0910-8327
Nutrition
117
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Dietary phytoestrogens and estrogen inhibit experimental atherosclerosis. Author(s): Center for Clinical and Basic Research, Ballerup Byvej 222, DK-2750 Ballerup, Denmark. Source: Alexandersen, P Haarbo, J Breinholt, V Christiansen, C Climacteric. 2001 June; 4(2): 151-9 1369-7137
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Do soy isoflavones lower cholesterol, inhibit atherosclerosis, and play a role in cancer prevention? Author(s): Department of Biological Sciences, Kingsborough Community College, City University of New York, Brooklyn, New York, USA. Source: Arliss, R M Biermann, C A Holist-Nurs-Pract. 2002 October; 16(5): 40-8 08879311
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Early feeding and atherosclerosis. Source: Mott, G.E. Long-term consequences of early feeding /. Philadelphia : LippincottRaven, c1996. page 113-122. ISBN: 0397517289
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Editorial Comment: MMP inhibition and the development of cerebrovascular atherosclerosis: The road ahead. Source: Napoli, C Stroke. 2002 December; 33(12): 2865 1524-4628
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Endothelin A receptor antagonist LU 135252 inhibits hypercholesterolemia-induced, but not deendothelialization-induced, atherosclerosis in rabbit arteries. Author(s): Department of Diagnostic Radiology, University of Tubingen, Germany.
[email protected] Source: Tepe, Gunnar Brehme, Ute Seeger, Harald Raschack, Manfred Claussen, Claus D Duda, Stephan H Invest-Radiol. 2002 June; 37(6): 349-55 0020-9996
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Environmental modulation of atherosclerosis end points in familial hypercholesterolemia. Author(s): Blackburn Cardiovascular Genetics Laboratory, John P. Robarts Research Institute, University of Western Ontario, 406-100 Perth Drive, London, ON, Canada N6A 5K8.
[email protected] Source: Hegele, Robert A Atheroscler-Suppl. 2002 March; 2(3): 5-7 1567-5688
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Estrogen and atherosclerosis. Author(s): Franz-Volhard-Klinik, Humboldt University of Berlin, Wiltbergstrasse 50, 13125 Berlin-Buch, Germany.
[email protected] Source: Luft, Friedrich C J-Mol-Med. 2002 March; 80(3): 133-4 0946-2716
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Evidence for grape, wine and tea polyphenols as modulators of atherosclerosis and ischemic heart disease in humans. Source: Dubick, M.A. Omaye, S.T. J-nutraceuticals-funct-med-foods. Binghamton, NY : Pharmaceutical Products Press, an imprint of the Haworth Press, Inc., c1997-. 2001. volume 3 (3) page 67-93. 1089-4179
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Genetic determinants of homocysteine thiolactonase activity in humans: implications for atherosclerosis. Author(s): Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
[email protected] Source: Jakubowski, H Ambrosius, W T Pratt, J H FEBS-Lett. 2001 Feb 23; 491(1-2): 35-9 0014-5793
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Genetic loci determining bone density in mice with diet-induced atherosclerosis. Author(s): Departments of Pathology and Laboratory Medicine, University of California, Los Angeles, California 90095, USA.
[email protected]
118 Atherosclerosis
Source: Drake, T A Schadt, E Hannani, K Kabo, J M Krass, K Colinayo, V Greaser , L E 3rd Goldin, J Lusis, A J Physiol-Genomics. 2001 April 27; 5(4): 205-15 1094-8341 •
Heat-shock proteins and atherosclerosis. Author(s): Immunoallergology Unit-Hospital Santa Maria-1699 Lisbon, Portugal. Source: Ferreira, M Branco Carlos, A G Palma Allerg-Immunol-(Paris). 2002 June; 34(6): 204-7 0397-9148
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Imaging of the endothelial dysfunction in coronary atherosclerosis. Author(s): Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and Niuvanniemi Hospital, Finland.
[email protected] Source: Kuikka, J T Raitakari, O T Gould, K L Eur-J-Nucl-Med. 2001 October; 28(10): 1567-78 0340-6997
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Impact of saturated and trans fatty acid enriched oil blends on atherosclerosis in rabbits fed cholesterol-free diets. Author(s): Palm Oil Research Institute of Malaysia (PORIM), Kuala Lumpur (Malaysia) Source: Sundram, K. Pathmanathan, R. Wong, K.T. Baskaran, G. Asia-Pacific-Journal-ofClinical-Nutrition (United Kingdom). (1997). volume 6(1) page 31-35.
•
Inflammatory mechanisms in atherosclerosis: from laboratory evidence to clinical application. Author(s): Center for Cardiovascular Disease Prevention, Department of Medicine, Brigham and Women's Hospital, Havard Medical School, Boston, MA 02215, USA. Source: Blake, G J Ridker, P M Ital-Heart-J. 2001 November; 2(11): 796-800 1129-471X
•
Interaction of the common apolipoprotein C-III (APOC3 -482C > T) and hepatic lipase (LIPC -514C > T) promoter variants affects glucose tolerance in young adults. European Atherosclerosis Research Study II (EARS-II). Author(s): Department of Internal Medicien, Erasmus University, Rotterdam, The Netherlands.
[email protected] Source: Jansen, H Waterworth, D M Nicaud, V Ehnholm, C Talmud, P J Ann-HumGenet. 2001 May; 65(Pt 3): 237-43 0003-4800
•
Lipid peroxidation in mouse models of atherosclerosis. Author(s): Center for Experimental Therapeutics, Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
[email protected] Source: Pratico, D Trends-Cardiovasc-Med. 2001 Apr-May; 11(3-4): 112-6 1050-1738
•
Lipids and atherosclerosis: clinical management of hypercholesterolaemia. Author(s): Alfred and Baker Medical Unit, Baker Medical Research Institute and Heart Centre, Alfred Hospital, Commercial Rd, Prahran 3181, Australia.
[email protected] Source: Chin Dusting, J P Shaw, J A Expert-Opin-Pharmacother. 2001 March; 2(3): 419-30 1465-6566
•
Lycopene, atherosclerosis, and coronary heart disease. Author(s): Research Institute of Public Health, University of Kuopio, Kuopio, Finland 70211.
[email protected] Source: Rissanen, T Voutilainen, S Nyyssonen, K Salonen, J T Exp-Biol-Med-(Maywood). 2002 November; 227(10): 900-7 1535-3702
•
Macrophage scavenger receptor (SR-A I/II) deficiency reduced diet-induced atherosclerosis in C57BL/6J mice. Author(s): Pharmaceutical Technology Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Nutrition
119
Source: Kamada, N Kodama, T Suzuki, H J-Atheroscler-Thromb. 2001; 8(1): 1-6 13403478 •
Mapping of microsatellite loci and association of aorta atherosclerosis with LG VI markers in the rabbit. Author(s): Department of Laboratory Animal Science, Faculty of Veterinary Medicine, Utrecht University, 3508 TD Utrecht, The Netherlands.
[email protected] Source: Korstanje, R Gillissen, G F Kodde, L P Den Bieman, M Lankhorst, A Van Zutphen, L F Van Lith, H A Physiol-Genomics. 2001 June 6; 6(1): 11-8 1094-8341
•
Mechanisms for oxidizing low-density lipoprotein. Insights from patterns of oxidation products in the artery wall and from mouse models of atherosclerosis. Author(s): Department of Medicine, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St. Louis, Missouri, USA. Source: Gaut, J P Heinecke, J W Trends-Cardiovasc-Med. 2001 Apr-May; 11(3-4): 103-12 1050-1738
•
Miscellaneous medications for the management of atherosclerosis: mayhem or miracle? Author(s): Mote Vascular Foundation, Sarasota, FL, USA. Source: Samson, R H Semin-Vasc-Surg. 2002 December; 15(4): 275-87 0895-7967
•
Non-invasive vascular detection of early signs of atherosclerosis in hypercholesterolemic children: why and how. Author(s): Dipartimento di Medicina Clinica e Sperimentale, Universita Federico II, Via S. Pansini 5, 80131 Napoli, Italy. Source: Rubba, P Iannuzzi, A Faccenda, F De Leo, F Pauciullo, P Nutr-MetabCardiovasc-Dis. 2001 October; 11 Suppl 5: 10-5 0939-4753
•
Oxidants and antioxidants in atherosclerosis. Author(s): Biochemistry Group, The Heart Research Institute, Sydney, Australia. Source: Mashima, R Witting, P K Stocker, R Curr-Opin-Lipidol. 2001 August; 12(4): 4118 0957-9672
•
Oxidized LDL-induced injury and apoptosis in atherosclerosis. Potential roles for oxysterols. Author(s): Departments of Biomedical Engineering and Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA. Source: Colles, S M Maxson, J M Carlson, S G Chisolm, G M Trends-Cardiovasc-Med. 2001 Apr-May; 11(3-4): 131-8 1050-1738
•
Paradoxical effects of vitamin E: oxidized lipoproteins, prostanoids and the pathogenesis of atherosclerosis. Source: Cornwell, D.G. Zhang, H. Davis, W.B. Whisler, R.L. Panganamala, R.V. NATOASI-ser,-Ser-A,-Life-sci. New York : Plenum, 1984-. 1990. volume 189 page 215-237. 02581213
•
Pentosidine, carotid atherosclerosis and alterations in left ventricular geometry in hemodialysis patients. Author(s): CNR, Centre of Clinical Physiology and Division of Nephrology, Reggio Calabria, Italy.
[email protected] Source: Zoccali, C Mallamaci, F Asahia, K Benedetto, F A Tripepi, G Tripepi, R Nicocia, G Buemi, M Miyata, T J-Nephrol. 2001 Jul-August; 14(4): 293-8 1120-3625
•
Pharmaceutical initiatives to combat atherosclerosis--what to do with the good, the bad, and the ugly lipoproteins. Author(s): Mote Vascular Foundation, Sarasota, FL, USA.
120 Atherosclerosis
Source: Samson, R H Semin-Vasc-Surg. 2002 December; 15(4): 204-15 0895-7967 •
Plasma homocysteine levels and atherosclerosis in Japan: epidemiological study by use of carotid ultrasonography. Author(s): Third Department of Internal Medicine and Cardiovascular Research Institute, Kurume University School of Medicine, Kurume, Japan.
[email protected] Source: Adachi, H Hirai, Y Fujiura, Y Matsuoka, H Satoh, A Imaizumi, T Stroke. 2002 September; 33(9): 2177-81 1524-4628
•
Platelet labelling in atherosclerosis. Source: Sinzinger, H. Virgolini, I. Fitscha, P. NATO-ASI-ser,-Ser-A,-Life-sci. New York : Plenum, 1984-. 1991. volume 219 page 181-188. 0258-1213
•
Protective effects of Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) against atherosclerosis in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. Author(s): Kampo & Pharmacognosy Laboratory, Tsumura & Co., Yoshiwara, Inashikigun, Ibaraki, 3586 Ami-machi, 300-1192 Japan.
[email protected] Source: Yoshie, F Iizuka, A Kubo, M Komatsu, Y Matsumoto, A Itakura, H Takeda, H Matsumiya, T Kondo, K Pharmacol-Res. 2001 May; 43(5): 481-8 1043-6618
•
Relevance of hypercholesterolemia to fetal and pediatric atherosclerosis. Author(s): Department of Pathology and Molecular Medicine, Wellington School of Medicine, New Zealand.
[email protected] Source: Stehbens, W E Pediatr-Pathol-Mol-Med. 2002 May-June; 21(3): 259-78 1522-7952
•
Role of 12-lipoxygenase and oxidant stress in hyperglycaemia-induced acceleration of atherosclerosis in a diabetic pig model. Author(s): Gonda Diabetes Center, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
[email protected] Source: NataraJanuary, R Gerrity, R G Gu, J L Lanting, L Thomas, L Nadler, J L Diabetologia. 2002 Jan; 45(1): 125-33 0012-186X
•
Studies of apoptosis and bcl-2 in experimental atherosclerosis in rabbit and influence of selenium supplementation. Author(s): Department of Biophysics, Panjab University, Chandigarh, India. Source: Mehta, U Kang, B P Bansal, G Bansal, M P Gen-Physiol-Biophys. 2002 March; 21(1): 15-29 0231-5882
•
The effect of antioxidant-containing fraction from fermented soybean food on atherosclerosis development in cholesterol-fed rabbits. Source: Yokota, T. Hattori, T. Ohishi, H. Hasegawa, K. Watanabe, K. Lebensm-WissTechnol. London : Academic Press. 1996. volume 29 (8) page 751-755. 0023-6438
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The fetal origins of atherosclerosis: maternal hypercholesterolemia, and cholesterollowering or antioxidant treatment during pregnancy influence in utero programming and postnatal susceptibility to atherogenesis. Author(s): Department of Medicine 0682, University of California San Diego, La Jolla, California 92093-0682, USA.
[email protected] Source: Palinski, W Napoli, C FASEB-J. 2002 September; 16(11): 1348-60 1530-6860
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The oxidative modification hypothesis of atherosclerosis: does it hold for humans? Author(s): Department of Medicine, Division of Endocrinology and Metabolism, Specialized Center of Research in Molecular Medicine and Atherosclerosis, University of California, San Diego School of Medicine, La Jolla, California, USA.
[email protected]
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Source: Witztum, J L Steinberg, D Trends-Cardiovasc-Med. 2001 Apr-May; 11(3-4): 93102 1050-1738 •
The total peroxyl radical trapping potential in serum - an assay to define the stage of atherosclerosis. Author(s): Nicolae Simionescu Institute of Cellular Biology and Pathology, Bucharest, Romania. Source: Niculescu, L Stancu, C Sima, A Toporan, D Simionescu, M J-Cell-Mol-Med. 2001 Jul-September; 5(3): 285-94 1582-1838
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The use of radiolabeled low density lipoprotein for evaluating atherosclerosis: present status and future promise. Source: Kay, R. NATO-ASI-ser,-Ser-A,-Life-sci. New York : Plenum, 1984-. 1991. volume 219 page 171-179. 0258-1213
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True deficiency of antioxidant vitamins E and A in dialysis patients. Relationship with clinical patterns of atherosclerosis. Author(s): Servicio de Nefrologia, Hospitales Universitarios La Paz, Spain. Source: Aguilera, A Bajo, M A del Peso, G Diez, J J Codoceo, R Rebollo, F Mariano, M Selgas, R Adv-Perit-Dial. 2002; 18: 206-11 1197-8554
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Vervet monkeys and whole-food diets for studying the effects of dietary lipids on plasma lipoprotein metabolism and atherosclerosis. Author(s): National Research Programme for Nutritional Intervention Medical Research Council, Tygerberg (South Africa) Source: Benade, A.J.S. Fincham, J.E. Smuts, C.M. Weight, M.J. Jaarsveld, P.J. van Kruger, M. Asia-Pacific-Journal-of-Clinical-Nutrition (United Kingdom). (1997). volume 6(1) page 17-21.
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Vitamin E, atherosclerosis and thrombosis. Author(s): Institute of Clinical Medicine I, University La Sapienza, Rome, Italy.
[email protected] Source: Violi, F Micheletta, F Iuliano, L Thromb-Haemost. 2001 May; 85(5): 766-70 03406245
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to atherosclerosis; 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: •
Vitamins Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Pantothenic Acid Source: Integrative Medicine Communications; www.drkoop.com Pantothenic Acid and Pantethine Source: Prima Communications, Inc.www.personalhealthzone.com Pyridoxine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B12 Source: Healthnotes, Inc.; www.healthnotes.com
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Vitamin B3 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B5 (pantothenic Acid) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B6 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B6 (pyridoxine) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B9 (folic Acid) Alternative names: Folate, Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin D Alternative names: Calciferol, Calcitrol, Cholecalciferol, Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com Vitamin D Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,905,00.html Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,906,00.html Vitamin K Alternative names: Menadione, Menaphthone, Menaquinone, Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com •
Minerals Betaine Hydrochloride Source: Prima Communications, Inc.www.personalhealthzone.com
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Calcium: Which Form Is Best? Source: Healthnotes, Inc.; www.healthnotes.com Carnitine Source: Prima Communications, Inc.www.personalhealthzone.com Chondroitin Source: Prima Communications, Inc.www.personalhealthzone.com Fluvastatin Source: Healthnotes, Inc.; www.healthnotes.com Folate Source: Integrative Medicine Communications; www.drkoop.com Folate Source: Prima Communications, Inc.www.personalhealthzone.com Gabapentin Source: Healthnotes, Inc.; www.healthnotes.com Iron Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Magnesium Source: Prima Communications, Inc.www.personalhealthzone.com Manganese Source: Integrative Medicine Communications; www.drkoop.com Quercetin Source: Healthnotes, Inc.; www.healthnotes.com Quercetin Source: Prima Communications, Inc.www.personalhealthzone.com Selenium Source: Healthnotes, Inc.; www.healthnotes.com Spironolactone Source: Healthnotes, Inc.; www.healthnotes.com •
Food and Diet Artichoke Alternative names: Cynara scolymus Source: Healthnotes, Inc.; www.healthnotes.com
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Asparagus Source: Healthnotes, Inc.; www.healthnotes.com Atkins Diet Source: Healthnotes, Inc.; www.healthnotes.com Beets Source: Healthnotes, Inc.; www.healthnotes.com Betaine (trimethylglycine) Source: Healthnotes, Inc.; www.healthnotes.com Brussels Sprouts Source: Healthnotes, Inc.; www.healthnotes.com Carrots Source: Healthnotes, Inc.; www.healthnotes.com Celery Source: Healthnotes, Inc.; www.healthnotes.com Chondroitin Sulfate Source: Healthnotes, Inc.; www.healthnotes.com Coffee Source: Healthnotes, Inc.; www.healthnotes.com Diabetes Source: Healthnotes, Inc.; www.healthnotes.com Fat Alternatives and Fat Replacers Source: Healthnotes, Inc.; www.healthnotes.com Flaxseeds Source: Healthnotes, Inc.; www.healthnotes.com Garlic Alternative names: Allium sativum Source: Healthnotes, Inc.; www.healthnotes.com Garlic Alternative names: Allium sativum Source: Integrative Medicine Communications; www.drkoop.com Garlic Source: Prima Communications, Inc.www.personalhealthzone.com Garlic Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,786,00.html
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High Cholesterol Source: Healthnotes, Inc.; www.healthnotes.com Kale Source: Healthnotes, Inc.; www.healthnotes.com Low-fat Diet Source: Healthnotes, Inc.; www.healthnotes.com Monounsaturated Fats Source: Healthnotes, Inc.; www.healthnotes.com Okra Source: Healthnotes, Inc.; www.healthnotes.com Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Omega-6 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Polyunsaturated Fats Source: Healthnotes, Inc.; www.healthnotes.com Pumpkin Seeds Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,176,00.html Soy Products Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,135,00.html Spinach Source: Healthnotes, Inc.; www.healthnotes.com Sweet Potatoes Source: Healthnotes, Inc.; www.healthnotes.com Tea Source: Healthnotes, Inc.; www.healthnotes.com The Dean Ornish Diet Source: Healthnotes, Inc.; www.healthnotes.com Trans-fats Source: Healthnotes, Inc.; www.healthnotes.com Turnips Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE ATHEROSCLEROSIS
MEDICINE
AND
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to atherosclerosis. 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 atherosclerosis 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 “atherosclerosis” (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 atherosclerosis: •
A risk factor for atherosclerosis: triglyceride-rich lipoproteins. Author(s): Malloy MJ, Kane JP. Source: Adv Intern Med. 2001; 47: 111-36. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795072&dopt=Abstract
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A water-extract of the Korean traditional formulation Geiji-Bokryung-Hwan reduces atherosclerosis and hypercholesteremia in cholesterol-fed rabbits. Author(s): Kim BJ, Kim YK, Park WH, Ko JH, Lee YC, Kim CH. Source: International Immunopharmacology. 2003 May; 3(5): 723-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757741&dopt=Abstract
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Accelerated atherosclerosis, dyslipidemia, and oxidative stress in end-stage renal disease. Author(s): Mathur S, Devaraj S, Jialal I. Source: Current Opinion in Nephrology and Hypertension. 2002 March; 11(2): 141-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11856905&dopt=Abstract
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Adverse effects of supplemental L-arginine in atherosclerosis: consequences of methylation stress in a complex catabolism? Author(s): Loscalzo J. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 January 1; 23(1): 3-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524215&dopt=Abstract
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Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis Prevention Study (VEAPS). Author(s): Hodis HN, Mack WJ, LaBree L, Mahrer PR, Sevanian A, Liu CR, Liu CH, Hwang J, Selzer RH, Azen SP; VEAPS Research Group. Source: Circulation. 2002 September 17; 106(12): 1453-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234947&dopt=Abstract
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Antioxidants and atherosclerosis: don't throw out the baby with the bath water. Author(s): Jialal I, Devaraj S. Source: Circulation. 2003 February 25; 107(7): 926-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600900&dopt=Abstract
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Antioxidants, statins, and atherosclerosis. Author(s): Gotto AM. Source: Journal of the American College of Cardiology. 2003 April 2; 41(7): 1205-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679223&dopt=Abstract
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Beneficial effects of a novel IH636 grape seed proanthocyanidin extract and a niacinbound chromium in a hamster atherosclerosis model. Author(s): Vinson JA, Mandarano MA, Shuta DL, Bagchi M, Bagchi D. Source: Molecular and Cellular Biochemistry. 2002 November; 240(1-2): 99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12487376&dopt=Abstract
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Biphasic modulation of atherosclerosis induced by graded dietary copper supplementation in the cholesterol-fed rabbit. Author(s): Lamb DJ, Avades TY, Ferns GA.
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Source: International Journal of Experimental Pathology. 2001 October; 82(5): 287-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11703538&dopt=Abstract •
Cholesterol vehicle in experimental atherosclerosis 24: avocado oil. Author(s): Kritchevsky D, Tepper SA, Wright S, Czarnecki SK, Wilson TA, Nicolosi RJ. Source: Journal of the American College of Nutrition. 2003 February; 22(1): 52-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12569114&dopt=Abstract
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Compared with saturated fatty acids, dietary monounsaturated fatty acids and carbohydrates increase atherosclerosis and VLDL cholesterol levels in LDL receptordeficient, but not apolipoprotein E-deficient, mice. Author(s): Merkel M, Velez-Carrasco W, Hudgins LC, Breslow JL. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 November 6; 98(23): 13294-9. Epub 2001 October 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11606787&dopt=Abstract
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Cranberry flavonoids, atherosclerosis and cardiovascular health. Author(s): Reed J. Source: Critical Reviews in Food Science and Nutrition. 2002; 42(3 Suppl): 301-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12058989&dopt=Abstract
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Daily melatonin supplementation in mice increases atherosclerosis in proximal aorta. Author(s): Tailleux A, Torpier G, Bonnefont-Rousselot D, Lestavel S, Lemdani M, Caudeville B, Furman C, Foricher R, Gardes-Albert M, Lesieur D, Rolando C, Teissier E, Fruchart JC, Clavey V, Fievet C, Duriez P. Source: Biochemical and Biophysical Research Communications. 2002 May 10; 293(3): 1114-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051775&dopt=Abstract
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Dietary linolenic acid and carotid atherosclerosis: the National Heart, Lung, and Blood Institute Family Heart Study. Author(s): Djousse L, Folsom AR, Province MA, Hunt SC, Ellison RC; National Heart, Lung, and Blood Institute Family Heart Study. Source: The American Journal of Clinical Nutrition. 2003 April; 77(4): 819-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663278&dopt=Abstract
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Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient mice. Author(s): Zhou J, Moller J, Danielsen CC, Bentzon J, Ravn HB, Austin RC, Falk E.
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Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2001 September; 21(9): 14706. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11557674&dopt=Abstract •
Do soy isoflavones lower cholesterol, inhibit atherosclerosis, and play a role in cancer prevention? Author(s): Arliss RM, Biermann CA. Source: Holistic Nursing Practice. 2002 October; 16(5): 40-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465217&dopt=Abstract
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Effect of a multimodality natural medicine program on carotid atherosclerosis in older subjects: a pilot trial of Maharishi Vedic Medicine. Author(s): Fields JZ, Walton KG, Schneider RH, Nidich S, Pomerantz R, Suchdev P, Castillo-Richmond A, Payne K, Clark ET, Rainforth M. Source: The American Journal of Cardiology. 2002 April 15; 89(8): 952-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950434&dopt=Abstract
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Effect of dietary supplementation with omega-3 fatty acids on progression of atherosclerosis in carotid arteries. Author(s): Angerer P, Kothny W, Stork S, von Schacky C. Source: Cardiovascular Research. 2002 April; 54(1): 183-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062374&dopt=Abstract
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Effect of phytosterols in dietary diacylglycerol on atherosclerosis in cholesterol-fed rabbits. Author(s): Meguro S, Hase T, Otsuka A, Tokimitsu I, Itakura H. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2003 July-August; 19(7-8): 6705. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831957&dopt=Abstract
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Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. Author(s): Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, Ouyang P, Thompson P, Tardif JC, Higginson L, Bittner V, Steffes M, Gordon DJ, Proschan M, Younes N, Verter JI. Source: Jama : the Journal of the American Medical Association. 2002 November 20; 288(19): 2432-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435256&dopt=Abstract
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Effects of vitamin supplementation and hyperhomocysteinemia on atherosclerosis in apoE-deficient mice. Author(s): Zhou J, Moller J, Ritskes-Hoitinga M, Larsen ML, Austin RC, Falk E.
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Source: Atherosclerosis. 2003 June; 168(2): 255-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801608&dopt=Abstract •
Estrogen replacement therapy, atherosclerosis, and vascular function. Author(s): Mikkola TS, Clarkson TB. Source: Cardiovascular Research. 2002 February 15; 53(3): 605-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861031&dopt=Abstract
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Hibiscus sabdariffa extract inhibits the development of atherosclerosis in cholesterolfed rabbits. Author(s): Chen CC, Hsu JD, Wang SF, Chiang HC, Yang MY, Kao ES, Ho YC, Wang CJ. Source: Journal of Agricultural and Food Chemistry. 2003 August 27; 51(18): 5472-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926900&dopt=Abstract
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Indigenous drugs and atherosclerosis. Author(s): Udupa SL. Source: Drugs Today (Barc). 2001 January; 37(1): 37-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783096&dopt=Abstract
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Inflammation and atherosclerosis: the value of the high-sensitivity C-reactive protein assay as a risk marker. Author(s): Jialal I, Devaraj S. Source: American Journal of Clinical Pathology. 2001 December; 116 Suppl: S108-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11993695&dopt=Abstract
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Lipid peroxidation and platelet activation in murine atherosclerosis. Author(s): Cyrus T, Tang LX, Rokach J, FitzGerald GA, Pratico D. Source: Circulation. 2001 October 16; 104(16): 1940-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11602498&dopt=Abstract
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Macrophages take up triacylglycerol-rich emulsions at a faster rate upon coincubation with native and modified LDL: An investigation on the role of natural chylomicrons in atherosclerosis. Author(s): Carvalho MD, Harada LM, Gidlund M, Ketelhuth DF, Boschcov P, Quintao EC. Source: Journal of Cellular Biochemistry. 2002; 84(2): 309-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11787060&dopt=Abstract
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Miscellaneous medications for the management of atherosclerosis: mayhem or miracle? Author(s): Samson RH.
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Source: Semin Vasc Surg. 2002 December; 15(4): 275-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478502&dopt=Abstract •
Modulation of monocyte-macrophage function with alpha-tocopherol: implications for atherosclerosis. Author(s): Devaraj S, Harris A, Jialal I. Source: Nutrition Reviews. 2002 January; 60(1): 8-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11843003&dopt=Abstract
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Molecular mechanisms by which dietary isoflavones potentially prevent atherosclerosis. Author(s): Cassidy A, De Pascual Teresa S, Rimbach G. Source: Expert Reviews in Molecular Medicine [electronic Resource]. 2003 September 30; 5: 1-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585174&dopt=Abstract
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Omega-3 fatty acids: their role in the prevention and treatment of atherosclerosis related risk factors and complications. Author(s): Bhatnagar D, Durrington PN. Source: Int J Clin Pract. 2003 May; 57(4): 305-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800463&dopt=Abstract
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Oral insulin supplementation attenuates atherosclerosis progression in apolipoprotein E-deficient mice. Author(s): Shamir R, Shehadeh N, Rosenblat M, Eshach-Adiv O, Coleman R, Kaplan M, Hamoud S, Lischinsky S, Hayek T. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 January 1; 23(1): 10410. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524232&dopt=Abstract
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Oral synthetic phospholipid (DMPC) raises high-density lipoprotein cholesterol levels, improves high-density lipoprotein function, and markedly reduces atherosclerosis in apolipoprotein E-null mice. Author(s): Navab M, Hama S, Hough G, Fogelman AM. Source: Circulation. 2003 October 7; 108(14): 1735-9. Epub 2003 September 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504179&dopt=Abstract
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Oxidative stress, alpha-tocopherol therapy, and atherosclerosis. Author(s): Harris A, Devaraj S, Jialal I. Source: Current Atherosclerosis Reports. 2002 September; 4(5): 373-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12162937&dopt=Abstract
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Oxidized fatty acids promote atherosclerosis only in the presence of dietary cholesterol in low-density lipoprotein receptor knockout mice. Author(s): Khan-Merchant N, Penumetcha M, Meilhac O, Parthasarathy S. Source: The Journal of Nutrition. 2002 November; 132(11): 3256-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421837&dopt=Abstract
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Plasma and dietary vitamin E in relation to incidence of type 2 diabetes: The Insulin Resistance and Atherosclerosis Study (IRAS). Author(s): Mayer-Davis EJ, Costacou T, King I, Zaccaro DJ, Bell RA; The Insulin Resistance and Atherosclerosis Study (IRAS). Source: Diabetes Care. 2002 December; 25(12): 2172-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453956&dopt=Abstract
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Premenopausal social status and hormone exposure predict postmenopausal atherosclerosis in female monkeys. Author(s): Kaplan JR, Manuck SB, Anthony MS, Clarkson TB. Source: Obstetrics and Gynecology. 2002 March; 99(3): 381-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11864663&dopt=Abstract
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Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study. Author(s): Salonen RM, Nyyssonen K, Kaikkonen J, Porkkala-Sarataho E, Voutilainen S, Rissanen TH, Tuomainen TP, Valkonen VP, Ristonmaa U, Lakka HM, Vanharanta M, Salonen JT, Poulsen HE; Antioxidant Supplementation in Atherosclerosis Prevention Study. Source: Circulation. 2003 February 25; 107(7): 947-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600905&dopt=Abstract
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Studies of apoptosis and bcl-2 in experimental atherosclerosis in rabbit and influence of selenium supplementation. Author(s): Mehta U, Kang BP, Bansal G, Bansal MP. Source: Gen Physiol Biophys. 2002 March; 21(1): 15-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12168721&dopt=Abstract
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The degree of unsaturation of dietary fatty acids and the development of atherosclerosis (review). Author(s): Moreno JJ, Mitjavila MT. Source: The Journal of Nutritional Biochemistry. 2003 April; 14(4): 182-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770642&dopt=Abstract
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The effect of n-3 fatty acids on coronary atherosclerosis: results from SCIMO, an angiographic study, background and implications. Author(s): von Schacky C, Baumann K, Angerer P.
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Source: Lipids. 2001; 36 Suppl: S99-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11838000&dopt=Abstract •
The importance of the relation between lipoprotein(a) and lipids for development of atherosclerosis and cardiovascular disease. Author(s): Dahlen GH, Ekstedt B. Source: Journal of Internal Medicine. 2001 September; 250(3): 265-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555135&dopt=Abstract
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The inhibitory effect of soy protein isolate on atherosclerosis in mice does not require the presence of LDL receptors or alteration of plasma lipoproteins. Author(s): Adams MR, Golden DL, Anthony MS, Register TC, Williams JK. Source: The Journal of Nutrition. 2002 January; 132(1): 43-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773506&dopt=Abstract
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Vitamin E reduces progression of atherosclerosis in low-density lipoprotein receptordeficient mice with established vascular lesions. Author(s): Cyrus T, Yao Y, Rokach J, Tang LX, Pratico D. Source: Circulation. 2003 February 4; 107(4): 521-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566360&dopt=Abstract
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Vitamin E Supplementation in Patients With Carotid Atherosclerosis. Reversal of Altered Oxidative Stress Status in Plasma But Not in Plaque. Author(s): Micheletta F, Natoli S, Misuraca M, Sbarigia E, Diczfalusy U, Iuliano L. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 October 30 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14592846&dopt=Abstract
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Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients. Author(s): Marcucci R, Zanazzi M, Bertoni E, Rosati A, Fedi S, Lenti M, Prisco D, Castellani S, Abbate R, Salvadori M. Source: Transplantation. 2003 May 15; 75(9): 1551-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792513&dopt=Abstract
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Vitamins and hormone therapy for coronary atherosclerosis. Author(s): Hathcock JN. Source: Jama : the Journal of the American Medical Association. 2003 February 26; 289(8): 982; Author Reply 982. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597741&dopt=Abstract
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Whole-grain intake and insulin sensitivity: the Insulin Resistance Atherosclerosis Study.
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Author(s): Liese AD, Roach AK, Sparks KC, Marquart L, D'Agostino RB Jr, Mayer-Davis EJ. Source: The American Journal of Clinical Nutrition. 2003 November; 78(5): 965-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594783&dopt=Abstract •
Wine flavonoids protect against LDL oxidation and atherosclerosis. Author(s): Aviram M, Fuhrman B. Source: Annals of the New York Academy of Sciences. 2002 May; 957: 146-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074969&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to atherosclerosis; 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 Angina Source: Healthnotes, Inc.; www.healthnotes.com Arteriosclerosis Source: Integrative Medicine Communications; www.drkoop.com
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Atherosclerosis Source: Healthnotes, Inc.; www.healthnotes.com Atherosclerosis Source: Integrative Medicine Communications; www.drkoop.com Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com Cancer Prevention (reducing the Risk) Source: Prima Communications, Inc.www.personalhealthzone.com Cardiomyopathy Source: Healthnotes, Inc.; www.healthnotes.com Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.com Cataracts (prevention) Source: Prima Communications, Inc.www.personalhealthzone.com Chronic Obstructive Pulmonary Disease Source: Healthnotes, Inc.; www.healthnotes.com Congestive Heart Failure Source: Integrative Medicine Communications; www.drkoop.com Congestive Heart Failure Source: Prima Communications, Inc.www.personalhealthzone.com Coronary Artery Disease Source: Integrative Medicine Communications; www.drkoop.com Diabetes Source: Prima Communications, Inc.www.personalhealthzone.com Diabetes Mellitus Source: Integrative Medicine Communications; www.drkoop.com Erectile Dysfunction Source: Healthnotes, Inc.; www.healthnotes.com Gout Source: Integrative Medicine Communications; www.drkoop.com Heart Attack Source: Healthnotes, Inc.; www.healthnotes.com Heart Attack Source: Integrative Medicine Communications; www.drkoop.com
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High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Prima Communications, Inc.www.personalhealthzone.com High Homocysteine Source: Healthnotes, Inc.; www.healthnotes.com High Triglycerides Source: Healthnotes, Inc.; www.healthnotes.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com Hypertension Alternative names: High Blood Pressure Source: Prima Communications, Inc.www.personalhealthzone.com Impotence Source: Prima Communications, Inc.www.personalhealthzone.com Insulin Resistance Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Intermittent Claudication Source: Healthnotes, Inc.; www.healthnotes.com Intermittent Claudication Alternative names: Peripheral Vascular Disease Source: Prima Communications, Inc.www.personalhealthzone.com Macular Degeneration Source: Prima Communications, Inc.www.personalhealthzone.com Menopausal Symptoms (other Than Osteoporosis) Source: Prima Communications, Inc.www.personalhealthzone.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Myocardial Infarction Source: Integrative Medicine Communications; www.drkoop.com Pericarditis Source: Integrative Medicine Communications; www.drkoop.com Peripheral Vascular Disease Source: Healthnotes, Inc.; www.healthnotes.com Pulmonary Edema Source: Integrative Medicine Communications; www.drkoop.com
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Pulmonary Hypertension Source: Integrative Medicine Communications; www.drkoop.com Sickle Cell Anemia Source: Healthnotes, Inc.; www.healthnotes.com Stroke Source: Healthnotes, Inc.; www.healthnotes.com Stroke Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Healthnotes, Inc.; www.healthnotes.com Tias Source: Integrative Medicine Communications; www.drkoop.com Transient Ischemic Attacks Source: Integrative Medicine Communications; www.drkoop.com •
Alternative Therapy Cell Therapy Source: Healthnotes, Inc.; www.healthnotes.com Chelation Therapy Source: Healthnotes, Inc.; www.healthnotes.com Chelation Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,679,00.html Meditation Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,717,00.html Nutrition Source: Integrative Medicine Communications; www.drkoop.com
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Herbs and Supplements Alfalfa Alternative names: Medicago sativa Source: Healthnotes, Inc.; www.healthnotes.com Allium Sativum Source: Integrative Medicine Communications; www.drkoop.com
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Alpha-linolenic Acid (ala) Source: Integrative Medicine Communications; www.drkoop.com Amiloride Source: Healthnotes, Inc.; www.healthnotes.com Ananas Comosus Source: Integrative Medicine Communications; www.drkoop.com Angelica Sinensis Source: Integrative Medicine Communications; www.drkoop.com Anticonvulsants Source: Healthnotes, Inc.; www.healthnotes.com Antioxidants Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10004,00.html Antioxidants and Free Radicals Source: Healthnotes, Inc.; www.healthnotes.com Aortic Glycosaminoglycans Source: Prima Communications, Inc.www.personalhealthzone.com Arginine Source: Prima Communications, Inc.www.personalhealthzone.com Arginine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10005,00.html Astragalus Source: Prima Communications, Inc.www.personalhealthzone.com Beta-carotene Source: Healthnotes, Inc.; www.healthnotes.com Beta-sitosterol Source: Healthnotes, Inc.; www.healthnotes.com Bilberry Alternative names: Vaccinium myrtillus Source: Healthnotes, Inc.; www.healthnotes.com Bilberry Source: Prima Communications, Inc.www.personalhealthzone.com
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Bromelain Alternative names: Ananas comosus, Bromelainum Source: Integrative Medicine Communications; www.drkoop.com Bromelainum Source: Integrative Medicine Communications; www.drkoop.com Butcher’s Broom Alternative names: Ruscus aculeatus Source: Healthnotes, Inc.; www.healthnotes.com Calciferol Source: Integrative Medicine Communications; www.drkoop.com Calcitrol Source: Integrative Medicine Communications; www.drkoop.com Camellia Sinensis Source: Integrative Medicine Communications; www.drkoop.com Cephalosporins Source: Integrative Medicine Communications; www.drkoop.com Chinese Angelica Source: Integrative Medicine Communications; www.drkoop.com Cholecalciferol Source: Integrative Medicine Communications; www.drkoop.com Cholesterol-lowering Drugs Source: Healthnotes, Inc.; www.healthnotes.com Clopidogrel Source: Healthnotes, Inc.; www.healthnotes.com Colloidal Silver Source: Healthnotes, Inc.; www.healthnotes.com Conjugated Linoleic Acid Source: Healthnotes, Inc.; www.healthnotes.com Cornus Alternative names: Dogwood; Cornus florida & officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Crataegus Alternative names: Hawthorn; Crataegus oxyacantha L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Crataegus Laevigata Source: Integrative Medicine Communications; www.drkoop.com
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Crataegus Monogyna Source: Integrative Medicine Communications; www.drkoop.com Danggui Alternative names: Angelica sinensis, Chinese Angelica, Dang Gui, Danngui, Dong Qua, Tang Kuei, Tan Kue Bai zhi(Note: Dong quai should not be confused with Angelica root or Angelica seed.) Source: Integrative Medicine Communications; www.drkoop.com Dehydroepiandrosterone (dhea) Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (dhea) Source: Integrative Medicine Communications; www.drkoop.com Dhea Source: Integrative Medicine Communications; www.drkoop.com Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Dong Quai Alternative names: Angelica sinensis, Chinese Angelica, Dang Gui, Danngui, Dong Qua, Tang Kuei, Tan Kue Bai zhi(Note: Dong quai should not be confused with Angelica root or Angelica seed.) Source: Integrative Medicine Communications; www.drkoop.com Ephedra Source: Prima Communications, Inc.www.personalhealthzone.com Erocalciferol Source: Integrative Medicine Communications; www.drkoop.com Fenofibrate Source: Healthnotes, Inc.; www.healthnotes.com Fenugreek Alternative names: Trigonella foenum-graecum Source: Healthnotes, Inc.; www.healthnotes.com Flavonoids Source: Healthnotes, Inc.; www.healthnotes.com Flaxseed Alternative names: Linum usitatissimum, Linseed Source: Integrative Medicine Communications; www.drkoop.com Fo-ti Alternative names: Polygonum multiflorum Source: Healthnotes, Inc.; www.healthnotes.com
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Ginger Alternative names: Zingiber officinale Source: Healthnotes, Inc.; www.healthnotes.com Ginger Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ginkgo Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Biloba Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Biloba Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,788,00.html Grape Seed Alternative names: Vitis vinifera Source: Integrative Medicine Communications; www.drkoop.com Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc.; www.healthnotes.com Green Tea Alternative names: Camellia sinensis Source: Integrative Medicine Communications; www.drkoop.com Guggul Alternative names: Commiphora mukul Source: Healthnotes, Inc.; www.healthnotes.com Guggul Source: Prima Communications, Inc.www.personalhealthzone.com Gugulipid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10033,00.html Hawthorn Alternative names: Crataegus monogyna, Crataegus laevigata Source: Integrative Medicine Communications; www.drkoop.com Hawthorn Source: Prima Communications, Inc.www.personalhealthzone.com
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Hibiscus Alternative names: Hibiscus, Roselle; Hibiscus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Linseed Source: Integrative Medicine Communications; www.drkoop.com Linum Usitatissimum Source: Integrative Medicine Communications; www.drkoop.com Loop Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Lutein Source: Prima Communications, Inc.www.personalhealthzone.com Lycopene Source: Healthnotes, Inc.; www.healthnotes.com Menadione Source: Integrative Medicine Communications; www.drkoop.com Menaphthone Source: Integrative Medicine Communications; www.drkoop.com Menaquinone Source: Integrative Medicine Communications; www.drkoop.com Methionine Source: Healthnotes, Inc.; www.healthnotes.com Methionine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10084,00.html Olive Leaf Alternative names: Olea europa Source: Healthnotes, Inc.; www.healthnotes.com OPCS (Oligomeric Proanthocyanidins) Source: Prima Communications, Inc.www.personalhealthzone.com Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com Progesterone Source: Healthnotes, Inc.; www.healthnotes.com
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Psyllium Alternative names: Plantago ovata, Plantago ispaghula Source: Healthnotes, Inc.; www.healthnotes.com Red Clover Alternative names: Trifolium pratense , beebread, cow clover, cow grass, meadow clover, purple clover Source: Integrative Medicine Communications; www.drkoop.com Reishi Alternative names: Ganoderma lucidum Source: Healthnotes, Inc.; www.healthnotes.com Resveratrol Source: Healthnotes, Inc.; www.healthnotes.com Resveratrol Source: Prima Communications, Inc.www.personalhealthzone.com Rosemary Alternative names: Rosmarinus officinalis Source: Healthnotes, Inc.; www.healthnotes.com Royal Jelly Source: Healthnotes, Inc.; www.healthnotes.com Same Source: Healthnotes, Inc.; www.healthnotes.com Tang Kuei Source: Integrative Medicine Communications; www.drkoop.com Thiazide Diuretics Source: Healthnotes, Inc.; www.healthnotes.com Ticlopidine Source: Healthnotes, Inc.; www.healthnotes.com Tmg (trimethylglycine) Source: Prima Communications, Inc.www.personalhealthzone.com Tocotrienols Source: Healthnotes, Inc.; www.healthnotes.com Triamterene Source: Healthnotes, Inc.; www.healthnotes.com Turmeric Alternative names: Curcuma longa Source: Healthnotes, Inc.; www.healthnotes.com
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Turmeric Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10062,00.html Valproic Acid Source: Healthnotes, Inc.; www.healthnotes.com Vitis Vinifera Source: Integrative Medicine Communications; www.drkoop.com Warfarin Source: Healthnotes, Inc.; www.healthnotes.com Zingiber Alternative names: Ginger; Zingiber officinale Roscoe Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON ATHEROSCLEROSIS Overview In this chapter, we will give you a bibliography on recent dissertations relating to atherosclerosis. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “atherosclerosis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on atherosclerosis, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Atherosclerosis ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to atherosclerosis. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Antiphospholipid Antibodies and Atherosclerosis by Nicolo, Danielle M.; Phd from Temple University, 2002, 150 pages http://wwwlib.umi.com/dissertations/fullcit/3079135
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Characterizing Coronary Atherosclerosis with Intravascular Ultrasound by Nair, Anuja; Phd from Case Western Reserve University, 2003, 189 pages http://wwwlib.umi.com/dissertations/fullcit/3086247
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Determinants of the Longitudinal Change in Heart Rate Variability: the Atherosclerosis Risk in Communities Study by Schroeder, Emily Bartlett; Phd from The University of North Carolina at Chapel Hill, 2003, 278 pages http://wwwlib.umi.com/dissertations/fullcit/3086619
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Development of in Vivo Raman Spectroscopy of Atherosclerosis by Motz, Jason Taylor; Phd from Massachusetts Institute of Technology, 2003 http://wwwlib.umi.com/dissertations/fullcit/f112913
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Dietary Oxidized Linoleic Acid (13-hode) and Atherosclerosis: a Two-faced Janus by Khan-merchant, Nadya S.; Phd from Emory University, 2002, 201 pages http://wwwlib.umi.com/dissertations/fullcit/3050111
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Effect of the Homocysteine on Timp-1 and Metalloproteinase-2 Vascular Expression. Implications in Atherosclerosis (spanish Text) by Arias De Manuel, Roberto; Dr from Universidad De Navarra (spain), 2002, 154 pages http://wwwlib.umi.com/dissertations/fullcit/f352033
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Effects of Dietary Protein on Cholesterol Metabolism and Atherosclerosis by Huff, Murray Walker; Phd from The University of Western Ontario (canada), 1978 http://wwwlib.umi.com/dissertations/fullcit/NK46031
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Endothelium-dependent Relaxation in Experimental Atherosclerosis in the Rabbit by Jayakody, R. L; Phd from University of Alberta (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL45679
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Genetic and Environmental Predictors of Hdl Cholesterol and Atherosclerosis in the Nhlbi Family Heart Study (fhs) and the Atherosclerosis Risk in Communities (aric) Study by Peacock, James Matthew; Phd from University of Minnesota, 2002, 145 pages http://wwwlib.umi.com/dissertations/fullcit/3072681
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Interactions between the Guanine Nucleotide Exchange Factor, Vav2, the Plateletderived Growth Factor Receptor-beta and Phosphoinositide 3-kinase in Coronary Artery Vascular Smooth Muscle Cells: Functional Implications in Atherosclerosis by Cushman-vokoun, Allison Marie; Phd from University of Nebraska Medical Center, 2002, 233 pages http://wwwlib.umi.com/dissertations/fullcit/3068768
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Mechanisms of the Beneficial Effect of Estrogen on Subclinical Atherosclerosis: Lipids, Carbohydrate Metabolism and Blood Pressure by Karim, Roksana; Ms from University of Southern California, 2002, 29 pages http://wwwlib.umi.com/dissertations/fullcit/1411792
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Phosphoglucoisomerase Activity and Connective Tissue Changes in the Human Aorta during Atherosclerosis by Anastassiades, Tassos; Advdeg from Mcgill University (canada), 1966 http://wwwlib.umi.com/dissertations/fullcit/NK00296
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Primary Prevention of Atherosclerosis and Obesity in Young Adults Using Dietary and Educational Interventions by Matvienko, Oksana Alexandrovna; Phd from Iowa State University, 2002, 138 pages http://wwwlib.umi.com/dissertations/fullcit/3061845
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Progression of Carotid Intima-media Thickness and Plasma Antioxidants: the Los Angeles Atherosclerosis Study (california) by Fan, Jing; , Ms from University of Southern California, 2002, 26 pages http://wwwlib.umi.com/dissertations/fullcit/1411785
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Social Incongruity, Vocational Relationships, and Locus of Control in Coronaryprone Behavior and Atherosclerosis. by Ledom, Wesley Max, Phd from University of Missouri - Kansas City, 1978, 135 pages http://wwwlib.umi.com/dissertations/fullcit/7900007
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Surface Properties of the Arterial Wall and Their Relevance to Atherosclerosis by Boyce, John Frederick; Phd from The University of Western Ontario (canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK66046
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The Effect of Exercise on Atherosclerosis in the Abdominal Aorta and Coronary Artery of Mature Swine. by Gass, Gregory Charles, Phd from University of Illinois at Urbana-champaign, 1974, 150 pages http://wwwlib.umi.com/dissertations/fullcit/7414537
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The Effects of Vasectomy and Exercise upon Arterial Extensibility and the Extent and Severity of Atherosclerosis by Bridges, Francis Stephen, Edd from The University of Alabama, 1982, 146 pages http://wwwlib.umi.com/dissertations/fullcit/8314018
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The Relationship between Insulin Resistance Syndrome, Body Fat Distribution, Dietary Intake Variables and Subclinical Atherosclerosis in Obese Type 2 Diabetes by Hegazi, Refaat Mohamed; Phd from University of Pittsburgh, 2002, 179 pages http://wwwlib.umi.com/dissertations/fullcit/3054285
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The Role of Fatty Acid Binding Proteinap2 in Atherosclerosis and Macrophage Biology by Hayes, Liza Makowski; Phd from Harvard University, 2003, 220 pages http://wwwlib.umi.com/dissertations/fullcit/3076892
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The Role of Lecithin Cholesterol Acyltransferase on Atherosclerosis Development in the Mouse Model by Furbee, James Walter, Jr.; Phd from Wake Forest University, the Bowman Gray School of Medicine, 2002, 339 pages http://wwwlib.umi.com/dissertations/fullcit/3043099
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The Role of Liver X Receptors in Atherosclerosis by Joseph, Sean Barry; Phd from University of California, Los Angeles, 2002, 130 pages http://wwwlib.umi.com/dissertations/fullcit/3059599
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Validation of the Gerbil As an Animal Model for Human Atherosclerosis: Examination of Selected Risk Factors by Difrancesco, Loretta; Phd from University of Guelph (canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL52051
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND ATHEROSCLEROSIS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning atherosclerosis.
Recent Trials on Atherosclerosis The following is a list of recent trials dedicated to atherosclerosis.8 Further information on a trial is available at the Web site indicated. •
ARISE - Aggressive Reduction of Inflammation Stops Events Condition(s): Atherosclerosis; Coronary Artery Disease; Myocardial Infarction; Unstable Angina Study Status: This study is currently recruiting patients. Sponsor(s): AtheroGenics Purpose - Excerpt: To assess the safety and efficacy of AGI-1067, as compared to placebo, in the treatment of vascular inflammation and atherosclerosis by assessing the reduction in cardiovascular events. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066898
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Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Condition(s): Lupus Erythematosus, Systemic Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
8
These are listed at www.ClinicalTrials.gov.
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Purpose - Excerpt: High cholesterol levels are common in people with Systemic Lupus Erythematosus (SLE). Atorvastatin is a drug that reduces cholesterol levels. This study will test whether atorvastatin can reduce cholesterol levels in children with SLE. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065806 •
Cardiovascular Evaluation of Patients with High Cholesterol and Normal Volunteers Condition(s): Atherosclerosis; Hypercholesterolemia Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Homozygous familial hypercholesterolemia is a rare inherited disease of metabolism. It occurs in less than 1 in 1 million people within the United States. Patients with the disease are typically children and young adults who develop heart disease early in life. Children less than age 5 years with this disease have suffered heart attacks and death. The normal process that removes cholesterol particles from the blood stream does not work in patients with this disease. It causes cholesterol to buildup in the arteries and leads to hardening of the arteries (atherosclerosis). The goal of this study is to detect and measure atherosclerosis in these patients before it becomes permanent and potentially life threatening. Patients with this disease can participate in this study. Researchers plan to evaluate patients with homozygous familial hypercholesterolemia using new and standard methods for detecting atherosclerosis. Researchers plan to use information gathered during this study to develop new, promising treatments such as liver transplantation and gene therapy. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001204
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Effect of High Dose Vitamin E on Carotid Atherosclerosis Condition(s): Cardiovascular Diseases Study Status: This study is currently recruiting patients. Sponsor(s): National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The primary aim of the present study is to test the effect of alphatocopherol supplementation on the progression of carotid atherosclerosis in patients with coronary artery disease Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00010699
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Lipoprotein Metabolism in Normal Volunteers and Patients with High Levels of Lipoproteins Condition(s): Abetalipoproteinemia; Atherosclerosis; Healthy; Inborn Errors Lipid Metabolism Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Researchers plan to study the fat-rich particles, called lipoproteins, which circulate in the blood. This study is designed to improve understanding of normal, as well as abnormal, lipoprotein metabolism and the role it plays in the development of hardening of the arteries (atherosclerosis). Patients participating in this study will receive injections of lipoproteins or apolipoproteins (the protein component of lipoproteins) that have been isolated and purified. These lipoproteins will be labeled with small amounts of radioactive material and sterilized before they are injected into the patient. Patients participating in the study will be required to have blood samples taken, and provide urine samples throughout the course of the study. In addition, patient will be required to follow a specially formulated diet. Patients will be weighed throughout the course of the study. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001154
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Magnetic Resonance Angiography (MRA) for the Diagnosis of Atherosclerosis Condition(s): Atherosclerosis Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: Magnetic Resonance Angiography (MRA) is a method used to evaluate arteries and veins without the use of invasive catheters or x-rays (radiation). MRA technique has been continuously improving and has become more accurate at diagnosing problems of narrowing in blood vessels. However, MRA has a difficult time detecting narrowing in small blood vessels, limiting its use to large arteries. The purpose of this study is to recruit patients diagnosed with or suspected of having, atherosclerosis (hardening of the arteries) to participate in a series of new state-of-the-art diagnostic tests using MRA. This study is a combined effort between the National Institutes of Health (NIH), Uniformed Services University of the Health Sciences (USUHS), and General Electric Medical Services and is supported a Cooperative Research Agreement is to (CRADA). The goal of this study is to improve MRA to the point that it can reliably replace diagnostic x-ray catheter angiography in the evaluation of patients with atherosclerosis. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001841
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Prevention of Atherosclerosis and Heart Disease in Patients with Systemic Lupus Erythematosis (SLE) Condition(s): Systemic Lupus Erythematosus; Lupus
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Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Purpose - Excerpt: The purpose of this study is to find the best way to prevent heart disease and stroke in people with lupus (systemic lupus erythematosis, or SLE). The study will evaluate the effectiveness of medication and a phone-based education program in controlling four risk factors for heart disease: smoking, obesity, high blood pressure, and inactivity. The study will also test the safety of commonly used heart medications in people with lupus. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054938 •
Stop Atherosclerosis in Native Diabetics Study (SANDS) Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Diabetes Mellitus; Hypertension Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To compare aggressive lowering of low density lipoprotein (LDL) cholesterol and blood pressure to the usual care standard in Native American diabetics. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00047424
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Androgens and Subclinical Atherosclerosis in Young Women - Ancillary to CARDIA Condition(s): Cardiovascular Diseases; Coronary Arteriosclerosis; Heart Diseases; Polycystic Ovary Syndrome Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine whether serum androgens, measured earlier in life, and variation in genes related to androgen synthesis, metabolism, and signaling are associated with early-onset subclinical coronary atherosclerosis in young adult women from the community. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037245
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Atherosclerosis in Rheumatoid Arthritis Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Inflammation; Arthritis, Rheumatoid Study Status: This study is no longer recruiting patients.
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Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To test the theory that accelerated inflammation-promoted atherosclerosis occurs in patients with rheumatoid arthritis (RA). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037336 •
Atherosclerosis Risk in Communities (ARIC) Condition(s): Atherosclerosis; Coronary Disease; Coronary Heart Disease Risk Reduction; Diabetes Mellitus; Cardiovascular Diseases; Heart Diseases; Heart Failure, Congestive; Heart Failure Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To measure associations of established and suspected coronary heart disease risk factors with both atherosclerosis and new coronary heart disease events in representative cohorts from four diverse United States communities. To compare the communities with respect to risk factors, medical care, atherosclerosis, and coronary heart disease incidence. ARIC has two components in each community: study of representative cohorts of adult men and women, and community surveillance of morbidity and mortality. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005131
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Does the reduction of Total Body Iron Storage (TBIS) alter mortality in a population of patients with advanced PVD. Condition(s): Reduction of Total Body Iron Storage(TBIS); Atherosclerosis; Intermittent Claudication Study Status: This study is no longer recruiting patients. Sponsor(s): Department of Veterans Affairs; Department of Veterans Affairs Cooperative Studies Program Purpose - Excerpt: This study has successfully completed the feasibility phase. Fortyseven patients were enrolled at two sites. The results of the preliminary data indicated that the volumes of blood donated and the frequency of donation were well accepted by patients and safe. It also indicated that the formula for calculating volumes of blood to be removed to achieve the targeted reduction in Total Body Iron Stores (TBIS) was accurate and representative of the ferritin equivalence in storage iron found by others could be achieved. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032357
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Epidemiology of Carotid Artery Atherosclerosis in Youth Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Carotid Artery Diseases Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine the relationship of risk factors measured in childhood to intimal medial thickness (IMT) in early adulthood and to examine familial factors which may be related to increased IMT, a measure of atherosclerosis. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005397
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Epidemiology: Oxidative Stress and Early Atherosclerosis Condition(s): Cardiovascular Diseases; Heart Diseases; Atherosclerosis; Coronary Arteriosclerosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To measure serum concentrations of alpha tocopherol, selenium and all major carotenoids (alpha- and beta- carotene, lutein, (beta-cryptoxanthin and lycopene) in Black and white, male and female, high and low education individuals aged 18-30 in 1985-86. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005393
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Gene-by-Smoking Interactions and Risk of Atherosclerosis - Ancillary to ARIC Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Coronary Disease; Carotid Artery Diseases; Peripheral Vascular Diseases; Cerebral Arteriosclerosis; Cerebrovascular Accident Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate common genetic variations, that in combination with exposure to tobacco smoke, may modify the risk of atherosclerosis. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064545
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Genetics of Atherosclerosis in Mexican Americans Condition(s): Cardiovascular Diseases; Coronary Disease; Obesity; Atherosclerosis; Diabetes Mellitus, non-insulin dependent; Diabetes Mellitus Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI)
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Purpose - Excerpt: To identify individual genes that contribute to variation in susceptibility to coronary heart disease (CHD) in Mexican Americans. The program project grant supports the San Antonio Family Heart Study, the first comprehensive genetic epidemiological study of atherosclerosis and its correlates in Mexican Americans. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005462 •
Homocysteine and Progression of Atherosclerosis Condition(s): Cardiovascular Diseases; Peripheral Vascular Diseases; Atherosclerosis; Cerebrovascular Disorders; Myocardial Infarction; Heart Diseases; Hyperhomocysteinemia Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: In the first phase, to establish the relationship of progression of peripheral vascular disease (PVD) to plasma homocysteine. In the second phase, to conduct a randomized, controlled trial of folic acid treatment of plasma homocysteine in peripheral vascular disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005338
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Inflammation Genomics and Atherosclerosis - Ancillary to CARDIA Condition(s): Cardiovascular Diseases; Atherosclerosis; Coronary Arteriosclerosis; Inflammation; Heart Diseases; Thrombosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine the associations of common variation in inflammation/thrombosis genes with intermediate quantitative phenotypes and subclinical coronary atherosclerosis in the Coronary Artery Risk Factor Development in Young Adults (CARDIA) Study, a large, bi-racial cohort study. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00046605
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Insulin Resistance Atherosclerosis Study (IRAS) Condition(s): Cardiovascular Diseases; Atherosclerosis; Diabetes Mellitus; Heart Diseases; Obesity; Insulin Resistance Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To conduct a multicenter study of the relationship between insulin resistance and cardiovascular disease (CVD) and its risk factors in a tri-ethnic (African-
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American, Hispanic, and non-Hispanic white) population aged 40 to 69 years at baseline. Also, to identify the genetic determinants of insulin resistance and visceral adiposity. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005135 •
Intimal Thickening and Antioxidants in Hispanics and Anglos (Los Angeles Atherosclerosis Study) Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To investigate the role of serum and dietary antioxidants, serum prooxidants, and smoking on the progression/regression of carotid intima-media thickness (IMT). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005372
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Multi-Ethnic Study of Atherosclerosis (MESA) Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Coronary Arteriosclerosis; Coronary Disease; Cerebrovascular Accident; Myocardial Infarction; Heart Failure, Congestive; Heart Failure; Diabetes Mellitus, non-insulin dependent; Hypertension; Diabetes Mellitus Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To conduct a prospective observational study of the characteristics of subclinical cardiovascular disease (disease detected non-invasively before it has produced signs and symptoms) that predict progression to clinically overt cardiovascular disease in a diverse and representative population-based sample of men and women aged 35-84. Specifically the study shall: determine characteristics related to progression of subclinical to clinical cardiovascular disease; identify factors related to newer measures of subclinical disease and examine relationship of new to established measures; and develop population-based methods, suitable for application in future screening and intervention studies, for identifying asymptomatic persons at highest risk of clinical events. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005487
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Multi-Ethnic Study of Atherosclerosis (MESA) - Ancillary Eye Study Condition(s): Atherosclerosis; Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Cerebrovascular Disorders; Heart Failure, Congestive; Myocardial
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Infarction; Heart Diseases; Diabetes Mellitus, non-insulin dependent; Hypertension; Diabetic Retinopathy; Macular Degeneration; Diabetes Mellitus Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate the relation of retinal microvascular characteristics to subclinical cardiovascular disease, clinical disease, and their risk factors in the MultiEthnic Study of Atherosclerosis (MESA) cohort. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041444 •
Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Condition(s): Cardiovascular Diseases; Atherosclerosis; Heart Diseases; Coronary Disease; Coronary Arteriosclerosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To conduct a multicenter prevalence survey for characterizing pathologically the extent of atherosclerosis in the aortas and coronary arteries of young persons dying from accidental causes, suicide, or homicide. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005679
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Prevalence & Progression of Subclinical Atherosclerosis Condition(s): Atherosclerosis; Cardiovascular Diseases; Coronary Arteriosclerosis; Carotid Artery Diseases; Menopause Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate subclinical atherosclerotic disease in menopausal women. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006503
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Serum Sex Hormone Levels and Subclinical Atherosclerosis - Ancillary to MESA Condition(s): Cardiovascular Diseases; Atherosclerosis; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To assess the associations of serum sex hormones with the presence and progression of subclinical atherosclerosis. Study Type: Observational
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00064532 •
Adipose Distribution and Atherosclerosis Condition(s): Cardiovascular Diseases; Heart Diseases; Carotid Stenosis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To relate distribution of adipose tissue measured by a then new imaging technique, Magnetic Resonance Imaging (MRI) to extracranial carotid atherosclerosis, cardiovascular disease risk factors, and to more conventional measures of fat distribution such as body mass index (BMI) and waist/hip ratio. The primary hypothesis was that patients with extracranial carotid atherosclerosis (cases) had more intra-abdominal fat and a higher ratio of intra-abdominal fat to total or subcutaneous fat than age-sex-race matched controls. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005348
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Antioxidants and Prevention of Early Atherosclerosis Condition(s): Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Arteriosclerosis; Cerebrovascular Disorders; Heart Diseases; Vascular Diseases; Atherosclerosis Study Status: This study is suspended. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate the effects of vitamin E supplementation in retarding the progression of common carotid artery intima-media thickening in African Americans. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000600
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Apolipoprotein A-I Gene Polymorphism and Atherosclerosis Condition(s): Coronary Arteriosclerosis; Cardiovascular Diseases; Heart Diseases; Atherosclerosis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To further define the linkage of the Apo A-I gene polymorphism to genetic high density lipoprotein (HDL) deficiency and premature coronary artery disease. Also, to utilize this gene marker to define the prevalence of genetic HDL deficiency in patients with premature coronary disease and to determine the relative risk of premature coronary disease associated with the Apo A-I gene polymorphism. Study Type: Observational Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00005183 •
Assessment of a B-Mode Ultrasound Technique for the Measurement of Carotid Artery Intima-Media Thickness Condition(s): Atherosclerosis; Myocardial Infarction Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This minimal risk protocol is designed to assess the reproducibility of B-mode ultrasound measurements of carotid intima media thickness (IMT) when the scans are performed in CC Radiology and read using a computerized edge reader. Up to 20 volunteers will have two ultrasounds performed within a 6-month period. IMT thickness is used as a surrogate marker for atherosclerosis and may be of value in clinical trials. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001904
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Atherosclerosis and Omega-3 Fatty Acids in Alaskan Natives Condition(s): Cardiovascular Diseases; Heart Diseases; Atherosclerosis; Coronary Arteriosclerosis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine whether there were differences in the prevalence and extent of atherosclerotic lesions in the coronaries and aortas between Alaskan natives and non-natives, and whether the extent of the lesions was related to omega-3 fatty acids in blood and tissues. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005236
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Carotid Atherosclerosis Follow-up Study Condition(s): Cardiovascular Diseases; Carotid Artery Diseases; Myocardial Infarction; Coronary Disease; Heart Diseases; Cerebrovascular Accident Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine whether the degree of carotid artery atherosclerosis, as measured by B-mode ultrasound, predicts the development of myocardial infarction, stroke, and all-cause mortality in patients with angiographically defined coronary status. Also, to quantify the rate of progression of carotid artery disease and to evaluate the risk factors associated with progression of carotid atherosclerosis. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005189
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Cholesterol-Lowering Atherosclerosis Study (CLAS) Condition(s): Arterial Occlusive Diseases; Cardiovascular Diseases; Carotid Artery Diseases; Cerebral Arteriosclerosis; Cerebrovascular Disorders; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Ischemia; Atherosclerosis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine whether combined therapy with the lipid lowering agents colestipol hydrochloride plus niacin would produce significant change in coronary, carotid, and femoral artery atherosclerosis and coronary bypass graft lesions as determined by angiography. Also, to determine possible correlations between lesion changes and plasma lipid and lipoprotein cholesterol levels and to explore interrelationships of atherosclerosis change in femoral, coronary, and carotid arteries. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000599
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Comparison of Asymptomatic Carotid Atherosclerosis Between Frequent and Infrequent Blood Donors Condition(s): Carotid Atherosclerosis; Myocardial Infarction Study Status: This study is completed. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: Iron has been proposed to contribute to atherogenesis in humans by facilitating the oxidation of lipoproteins. This observational study will evaluate the association between frequency of blood donation - expected to be associated with relatively reduced body iron stores in frequent donors - and carotid atherosclerosis. The primary outcome variable will be whether the presence and extent of asymptomatic carotid atherosclerosis as measured by ultrasound is greater in infrequent (less than or equal to 1 donations/year greater than or equal to 5 years) vs. frequent (greater than or equal to 4 donations/year greater than or equal to 5 years) blood donors. Body iron stores, lipid and hemostatic parameters, nitric oxide formation, inflammatory parameters, and markers of vascular oxidative stress will be analyzed as secondary outcome measures. Laboratory analysis and ultrasound testing will be performed blinded to the patient's phlebotomy and iron status. Sixty frequent (n=40 males greater than 40 y/o, n=20 females greater than 50 y/o) and 60 infrequent (n=40 males greater than 40 y/o, n=20 females greater than 50 y/o) blood donors will be recruited for this study from the Department of Transfusion Medicine, W. G. Magnuson Clinical Center. All donors will be assessed for study eligibility and cardiovascular risks during the screening visit. The presence of atherosclerotic lesions by carotid ultrasound and secondary outcome parameters will be assessed during a second visit. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001589
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Comparison of Magnetic Resonance Angiography and Standard Angiography in Diagnosing Atherosclerosis Condition(s): Atherosclerosis Study Status: This study is completed. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will evaluate ways to improve magnetic resonance angiography (MRA) for diagnosing atherosclerosis (hardening and narrowing of the arteries). MRA is a new method for looking at arteries and veins without standard angiography, which requires inserting a catheter into a blood vessel, injecting a contrast material, and obtaining X-ray images. Current MRA techniques, however, do not depict the lumen (cavity) of small vessels well enough to accurately determine the extent of their narrowing. This study will test image processing methods with the eventual goal of improving MRA accuracy to the point that it can replace X-ray catheter angiography for diagnosing atherosclerotic disease. Patients with atherosclerosis who have had conventional angiography at Suburban Hospital in Bethesda, MD, may be considered for this study. They will be screened with a brief history and physical examination, and those enrolled will have a MRA scan within 72 hours of their conventional angiogram. For this procedure, a catheter is placed in a vein in the patient's arm and the patient lies on a table that slides into a magnetic resonance imaging (MRI) scanner-a large donutshaped machine with a magnetic field. Surface coils-flexible, padded antennae used to improve the quality of the pictures-are wrapped around the patient's legs. At times during the scan, the patient is asked to hold his or her breath for several seconds, and a contrast material called gadolinium is injected through the catheter in the vein. This substance enhances the images of blood flow in the vessels. The procedure generally takes about an hour and a half, although the actual imaging takes only a small part of that time. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001946
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Dietary Antioxidants and Atherosclerosis Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Carotid Stenosis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To examine the role of dietary antioxidants in the etiology of atherosclerosis in both sexes and in whites and Blacks. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005412
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Early Atherosclerosis Change in Two Clinical Trials Condition(s): Cardiovascular Diseases; Heart Diseases; Carotid Artery Diseases; Coronary Disease; Atherosclerosis Study Status: This study is completed.
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Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To complete end point analysis for the Monitored Atherosclerosis Regression Study (MARS) and to compare coronary versus carotid treatment effect relationships in MARS to coronary versus carotid treatment effect relationships in the Cholesterol Lowering Atherosclerosis Study (CLAS). Both MARS and CLAS were serial arterial imaging trials that explored the reversibility of atherosclerosis with lipidlowering therapy in native coronary, carotid, and femoral arterial beds, as well as in coronary artery bypass grafts. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005696 •
Effects of Hormone Replacement Therapy on Inflammation and Stiffening of Artery Walls Condition(s): Atherosclerosis; Healthy; Vascular Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will determine the effects of hormone replacement therapy (estrogen alone or estrogen and progesterone) on the walls of arteries in postmenopausal women. Inflammation and stiffness of artery walls are two risk factors for atherosclerosis-deposits of fatty substances (plaques) that can block the vessel, causing a heart attack or stroke. Estrogen raises the levels of certain substances in the blood that cause vessel inflammation and lowers the levels of others. This study will measure the net effects of estrogen on artery wall inflammation and stiffness. Postmenopausal women in good health may participate in this study. Volunteers will be screened for eligibility with a complete medical history, heart examination, and blood tests. Participants will be randomly assigned to receive either: 1) hormone therapy (estradiol 2 mg daily alone for women who have had a hysterectomy or estradiol plus micronized progesterone 200 mg daily for women with an intact uterus); or 2) placebo (look-alike pills that contain no active drug). Women in both groups will take pills for 3 months, then no pills for 1 month, and then will crossover to the alternate therapy for 3 months (i.e., those in the original placebo group will take hormones, and those in the hormone group will take placebo). At the end of each 3-month treatment period, participants will undergo the following procedures to assess blood vessel inflammation and stiffness: 1. Blood tests - 60 cc (about 2 ounces) of blood will be drawn to measure levels of hormones, cholesterol, and substances in the blood that indicate inflammation of the vessels. 2. Ultrasonography - an ultrasound probe will be applied gently on the neck to image the right and left carotid arteries (arteries in the neck that lead to the brain). During the procedure, the heart's electrical activity will also be monitored with an electrocardiogram and a blood pressure cuff will be wrapped around the arm to obtain blood pressure measurements every 5 minutes. 3. Magnetic resonance imaging (MRI) - Images of the carotid arteries are taken while the volunteer lies on a table in a narrow cylinder containing a magnetic field. A padded sensor called an MRI coil is placed over the neck and earplugs are placed in the ears to muffle the loud noise of the machine during scanning. During the second half of the exam, gadolinium is injected through a catheter (thin, flexible tube) inserted into a vein. Gadolinium is a contrast agent that is used to brighten the scan images. Information from this study will increase knowledge about the effects of estrogen on vessel wall inflammation. As such, it may be
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used in the future to help guide decisions about chronic hormone replacement therapy in postmenopausal women. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005108 •
Effects of Hormone Therapy on the Immune Systems of Postmenopausal Women with Chronic Infections Condition(s): Atherosclerosis; Chlamydia Infections; Cytomegalovirus Infections; Pneumonia, Bacterial; Postmenopause Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Hardening of the arteries (atherosclerosis) and heart disease are much more common in men than in women. However, as women grow older, especially after menopause the incidence of atherosclerosis and heart disease increases. These findings suggest that estrogen may be protective and help in preventing heart disease. Studies of large groups of post-menopausal women suggest that hormone replacement therapy (therapy that includes estrogen) reduces the risk of heart disease. Estrogen causes favorable changes in particles that carry cholesterol in the blood stream and improves function of blood vessels. Estrogen may also stimulate the immune system's ability to fight off infections that may lead to or contribute to atherosclerosis. Researchers believe two specific infectious agents (Chlamydia pneumoniae and human cytomegalovirus) may cause damage to the lining of blood vessels resulting in inflammation and the development of atherosclerosis. The purpose of this study is to determine if estrogen treatment can change how the immune system responds to chronic infections, by Chlamydia pneumoniae and human cytomegalovirus, in postmenopausal women. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001890
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Epidemiology of Atherosclerosis Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Coronary Arteriosclerosis Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine the role of genetic factors in predicting resistance and susceptibility to coronary artery disease. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005147
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Epidemiology of Plasma Fatty Acids and Atherosclerosis Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To measure by gas-liquid chromatography the relative concentrations of all saturated and unsaturated fatty acids found in the cholesterol ester and phospholipid fractions of plasma from 4,000 subjects participating in the Atherosclerosis Risk in Communities (ARIC) study. The data were used to clarify the role of various fatty acids in atherosclerosis. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005226
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Estrogen and Graft Atherosclerosis Research Trial (EAGER) Condition(s): Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Ischemia; Postmenopause Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine if postmenopausal hormone replacement therapy in women following coronary bypass surgery will reduce the occurrence of graft occlusion and delay the development of graft atherosclerosis. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000605
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Estrogen Replacement and Atherosclerosis (ERA) in Older Women Condition(s): Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Ischemia; Postmenopause Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine if estrogen replacement therapy, with or without low dose progesterone, slows progression or induces regression of coronary atherosclerosis in postmenopausal women. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000549
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Familial Atherosclerosis Treatment Study (FATS) Condition(s): Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Heart Diseases; Myocardial Ischemia
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Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To compare the effects of two intensive lipid-lowering regimens with conventional therapy on coronary atherosclerosis as assessed by arteriography. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000512 •
Harvard Atherosclerosis Reversibility Project (HARP) Condition(s): Cardiovascular Diseases; Coronary Disease; Heart Diseases; Myocardial Ischemia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine by sequential coronary arteriography whether a lipidlowering diet with and without lipid-lowering drugs could reverse coronary artery disease in normocholesterolemic patients. Also, to test whether fish oil supplements could improve human coronary atherosclerosis. Finally, to determine the effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and "normal" cholesterol levels. At least three clinical trials were conducted. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000461
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Magnetic Resonance Imaging to Detect Blood Vessel Inflammation in Patients Undergoing Peripheral Balloon Angioplasty Condition(s): Atherosclerosis; Peripheral Vascular Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will examine the use of magnetic resonance imaging (MRI) in detecting blood vessel inflammation. The results of this study may later be applied to diagnosing inflammation of arteries in patients with atherosclerosis, predicting disease progression in these patients, and guiding therapy. Patients with peripheral artery disease (for example, blockage of a leg artery) undergoing balloon angioplasty at Suburban Hospital in Bethesda, Maryland, may be eligible to participate in this study. Because this procedure, which opens blocked arteries, can cause inflammation in the vessel wall, it affords an opportunity for studying MRI detection of such inflammation. Study candidates will be screened with a medical history and physical examination. Participants will have a MRI scan and blood drawn at Suburban Hospital before the angioplasty and again either 1 to 3 days or 2 weeks after the procedure. Before the MRI scan is begun, a catheter (a thin plastic tube) is inserted in an arm vein and 90 milliliters (about 3 ounces) of blood is drawn. The patient then lies on a table that slides into the MRI scanner-a large donut-shaped machine with a magnetic field. A flexible, padded sensor called an MRI coil is placed over the area to be imaged;
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this device is used to improve the quality of the pictures. During the scan a contrast material called gadolinium is injected through the catheter. Gadolinium brightens the image of the blood vessels. The procedure lasts up to 2 hours. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004549 •
Postprandial Lipoproteins and Atherosclerosis Condition(s): Atherosclerosis; Cardiovascular Diseases; Heart Diseases; Carotid Artery Diseases; Myocardial Ischemia Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To determine whether postprandial lipoproteins were associated with atherosclerosis, and if so, whether the association was statistically independent of that between fasting lipoproteins and atherosclerosis. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005263
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Potential Risk Factors for Stroke Condition(s): Carotid Atherosclerosis; Cerebrovascular Accident; Diabetes Mellitus; Hypercholesterolemia; Hypertension Study Status: This study is completed. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: Early studies have shown that the immune system may play a role in the development of strokes. Conditions such as high blood pressure, high cholesterol, diabetes, and old age can activate the immune system and increase the risk of developing hardening of the arteries (atherosclerosis) and damaged blood vessels. Researchers will attempt to characterize factors that may contribute to atherosclerosis and stroke by measuring certain components of the immune system, cytokines and leukocyte activation. Measurements will be taken from patients that are considered to be stroke prone and from patients without risk factors for the development of stroke. Researchers will measure the immune system components at the beginning of the study, at six months, and at the one-year completion of the study. The study will attempt to determine; I) If patients with risk factors for stroke have an increased activation of the immune system II) If patients with risk factors for stroke that are symptomatic have higher levels of immune system activation compared to patients who do not have symptoms III) If patients with increased activation of the immune system have accelerated hardening of the arteries (atherosclerosis) Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001368
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•
Potential Role of CMV in Restenosis Following Angioplasty, in Atherosclerosis, and in Endothelial Dysfunction Condition(s): Arterial Occlusive Cytomegalovirus Infections
Diseases;
Atherosclerosis;
Coronary
Disease;
Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: The purpose of this study is to investigate whether the susceptibility of subjects to atherosclerosis is influenced by prior CMV exposure, whether the susceptability to endothelial dysfunction in patients with and in patients without atherosclerosis is influenced by prior CMV exposure. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001531 •
Study of the Interaction Between the Cells Lining Blood Vessels and AngiotensinConverting Enzyme Condition(s): Atherosclerosis; Coronary Disease Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: The walls of blood vessels are lined by flat cells that are responsible for releasing substance(s) that control the activity of the blood vessel. These cells are referred to as the endothelium of the blood vessel. One of the substances released from the endothelium is called nitric oxide (NO). This substance functions to keep blood vessels relaxed and to prevent blood from clotting inside the vessels. Studies done by researchers in the Cardiology Branch of the National Heart, Lung and Blood Institute have shown that nitric oxide activity may be lower in patients with hardening of the arteries (atherosclerosis) and risk factors for atherosclerosis. Another substance released by the cells of the endothelium is called bradykinin. It functions to stimulate the production of nitric oxide. Therefore bradykinin is also responsible for the relaxation and widening of blood vessels. An enzyme found in the blood called angiotensinconverting enzyme (ACE) inactivates baradykinin and thereby decreases the production of nitric oxide. The activity of ACE is determined by genetics and is different in each person. Medications that block ACE (ACE-inhibitors) may be useful for patients with high levels of ACE activity. This study is designed to determine; 1. The role of bradkinin in stimulating the production of nitric oxide 2. Whether ACE-inhibitors improve blood vessel relaxation caused by bradykinin 3. Whether ACE-inhibitors improve abnormal blood vessel relaxation 4. Whether ACE-inhibitors and bradykinin affect blood clotting 5. Whether blood vessel response to ACE-inhibitor and bradykinin depends on the patients genetic make-up Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001461
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Thickness of the Carotid Artery in HIV-Positive and HIV-Negative Adults Condition(s): HIV Infections; HIV Seronegativity; Atherosclerosis
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Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to see if there is a difference in the thickness of the carotid artery (the large artery in the neck) among HIV-positive participants taking protease inhibitors (PIs), HIV-positive participants not taking PIs, and HIV-negative participants. This study will also look at how the thickness in the carotid artery might change in these participants over time. The intima-media thickness (IMT) test uses sound waves to measure the thickness of the carotid artery. Studies have shown that this test may be able to predict a person's risk for heart disease. This study will use the IMT test to see if anti-HIV treatment and HIV infection affect a patient's risk of getting atherosclerosis (hardening of the arteries). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00007319
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “atherosclerosis” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON ATHEROSCLEROSIS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “atherosclerosis” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on atherosclerosis, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Atherosclerosis By performing a patent search focusing on atherosclerosis, 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 9Adapted
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 atherosclerosis: •
1, 3-bis-(substituted-phenyl)-2-propen-1-ones and their use to treat VCAM-1 mediated disorders Inventor(s): Hoong; Lee K. (Suwanee, GA), Meng; Charles Q. (Alpharetta, GA), Ni; Liming (Duluth, GA), Sikorski; James A. (Alpharetta, GA) Assignee(s): Atherogenics, Inc. (Alpharetta, GA) Patent Number: 6,608,101 Date filed: June 20, 2001 Abstract: It has been discovered certain 1,3-bis-(substituted-phenyl)-2-propen-1-ones, including compounds of formula (I) inhibit the expression of VCAM-1, and thus can be used to treat a patient with a disorder mediated by VCAM-1. Examples of inflammatory disorders that are mediated by VCAM-1 include, but are not limited to arthritis, asthma, dermatitis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, postangioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease. Excerpt(s): The present invention includes novel heteroaryl or heterocyclic 1,3-bis(substituted-phenyl)-2-propen-1-ones as well as methods and compositions for the treatment of disorders mediated by VCAM-1 or MCP-1 and for the treatment of inflammatory disorders generally that include the administration of a 1,3-bis(substituted-phenyl)-2-propen-1-one that has at least one phenyl substituent that is an aryl, heteroaryl or heterocyclic moiety. Adhesion of leukocytes to the endothelium represents a fundamental, early event in a wide variety of inflammatory conditions, autoimmune disorders and bacterial and viral infections. Leukocyte recruitment to endothelium is mediated in part by the inducible expression of adhesion molecules on the surface of endothelial cells that interact with counterreceptors on immune cells. Endothelial cells determine which types of leukocytes are recruited by selectively expressing specific adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin. VCAM-1 binds to the integrin VLA-4 expressed on lymphocytes, monocytes, macrophages, eosinophils, and basophils but not neutrophils. This interaction facilitates the firm adhesion of these leukocytes to the endothelium. VCAM-1 is an inducible gene that is not expressed, or expressed at very low levels, in normal tissues. VCAM-1 is upregulated in a number of inflammatory diseases, including arthritis, asthma, dermatitis, psoriasis, cystic fibrosis, post transplantation late and chronic solid organ rejection, multiple sclerosis, systemic lupus erythematosis, inflammatory bowel diseases, autoimmune diabetes, diabetic retinopathy, rhinitis, ischemia-reperfusion injury, post-angioplasty restenosis, chronic obstructive pulmonary disease (COPD), glomerulonephritis, Graves disease, gastrointestinal allergies, conjunctivitis, atherosclerosis, coronary artery disease, angina and small artery disease. Coronary heart disease (CHD), primarily as a result of atherosclerosis, remains the leading cause of death in industrialized countries. Atherosclerosis is a disease characterized by vascular inflammation, deposition of lipids in the arterial vessel wall and smooth muscle cell proliferation resulting in a narrowing of the vessel passages. In advanced stages of the disease atherosclerotic lesions can become unstable resulting in plaque rupture, thrombosis, myocardial infarction and
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ischemic heart disease. It is now well accepted that the initiating events in atherosclerosis are local injury to the arterial endothelium that results in the induction of VCAM-1 and recruitment of mononuclear leukocytes that express the integrin counterreceptor, VLA-4, (O'Brien, et al., J. Clin. Invest., 92: 945-951, 1993). Subsequent conversion of leukocytes to foamy macrophages results in the synthesis of a wide variety of inflammatory cytokines, growth factors, and chemoattractants that help propagate formation of the mature atheromatous plaque by further inducing endothelial activation, leukocyte recruitment, smooth muscle cell proliferation, and extracellular matrix deposition. Pharmacological inhibition of VCAM-1 expression has been shown to inhibit atherosclerosis in several animal models (Sundell et al., Circulation, 100: 42, 1999). A monoclonal antibody against VCAM-1 has also been shown to inhibit neointimal formation in a mouse model of arterial wall injury (Oguchi, S., et al., Arterioscler. Thromb. Vasc. Biol., 20: 1729-1736, 2000). Web site: http://www.delphion.com/details?pn=US06608101__ •
4-carboxyamino-2-substituted-1,2,3,4-tetrahydroquinolines Inventor(s): DeNinno; Michael P. (Gales Ferry, CT), Magnus-Aryitey; George T. (Ledyard, CT), Ruggeri; Roger B. (Waterford, CT), Wester; Ronald T. (Ledyard, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,586,448 Date filed: October 10, 2000 Abstract: Cholesteryl ester transfer protein inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDLcholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in some mammals, including humans. Excerpt(s): This invention relates to cholesteryl ester transfer protein (CETP) inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to elevate certain plasma lipid levels, including high density lipoprotein (HDL)-cholesterol and to lower certain other plasma lipid levels, such as low density lipoprotein (LDL)cholesterol and triglycerides and accordingly to treat diseases which are affected by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases in certain mammals (i.e., those which have CETP in their plasma), including humans. Atherosclerosis and its associated coronary artery disease (CAD) is the leading cause of mortality in the industrialized world. Despite attempts to modify secondary risk factors (smoking, obesity, lack of exercise) and treatment of dyslipidemia with dietary modification and drug therapy, coronary heart disease (CHD) remains the most common cause of death in the U.S., where cardiovascular disease accounts for 44% of all deaths, with 53% of these associated with atherosclerotic coronary heart disease. Risk for development of this condition has been shown to be strongly correlated with certain plasma lipid levels. While elevated LDL-C may be the most recognized form of dyslipidemia, it is by no means the only significant lipid associated contributor to CHD. Low HDL-C is also a known risk factor for CHD (Gordon, D. J., et al.,: "High-density Lipoprotein Cholesterol and Cardiovascular Disease", Circulation, (1989), 79: 8-15).
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Web site: http://www.delphion.com/details?pn=US06586448__ •
Androgen receptor modulators and methods for use thereof Inventor(s): Breslin; Michael J. (Drexel Hill, PA), Duggan; Mark E. (Schwenksville, PA), Halczenko; Wasyl (Lansdale, PA), Harada; Shun-Ichi (Ambler, PA), Hutchinson; John H. (La Jolla, CA), Rodan; Gideon A. (Bryn Mawr, PA), Sahoo; Soumya P. (Old Bridge, NJ), Schmidt; Azriel (Bryn Mawr, PA), Towler; Dwight A. (Brentwood, MO) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,645,974 Date filed: July 25, 2002 Abstract: Compounds of structural formula (I) as herein defined are disclosed as useful in a method for modulating the androgen receptor in a tissue selective manner in a patient in need of such modulation, as well as in a method of agonizing the androgen receptor in a patient, and in particular the method wherein the androgen receptor is antagonized in the prostate of a male patient or in the uterus of a female patient and agonized in bone and/or muscle tissue. These compounds are useful in the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including: osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, post-menopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, arthritis and joint repair, alone or in combination with other active agents. In addition, these compounds are useful as pharmaceutical composition ingredients alone and in combination with other active agents. Excerpt(s): Androgens play important roles in post-natal development that are most pronounced at adrenarche and pubarche. Androgen production promotes the musculoskeletal anabolism associated with the pubertal growth in both males and females. At puberty, ovarian and testicular androgens are responsible for pubertal hair, acne, and enhancement of libido. In males, exposure to 100-fold increased levels of endogenous androgens results in the gender dimorphism in bone mass, muscle mass (positive nitrogen balance), and upper body strength, and are required for normal sexual development (genitalia, spermatogenesis, prostate and seminal vesicle maturation). Delay in puberty decreases the peak bone mass achieved during adulthood. (Bhasin, S., et al., Eds. Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects. Wiley-Liss, Inc.:New York, 1996). In women, natural menopause causes virtually complete loss of ovarian estrogen production and gradually reduces ovarian production of androgen by approximately 50%. The physiological consequences of reduced androgen production after menopause are evident in decreased energy and libido, and contribute significantly in many women to vasomotor symptoms. Decreased androgen output is also thought to contribute-along with declining pituitary growth hormone (GH) secretion and insulin derived growth factor 1 (IGF1) action--to age-dependent sarcopenia, negative nitrogen balance and loss of bone mass. (Vestergaard, et al., Effect of sex hormone replacement on the insulin-like growth factor system and bone mineral: a cross-sectional and longitudinal study in 595 perimenopausal women participating in the Danish Osteoporosis Prevention Study, J Clin Endocrinol Metab. 84:2286-90, 1999; and Bhasin, et al., Eds. Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and
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Future Prospects, Wiley-Liss, Inc.:New York. 1996). Postmenopausal osteoporosis results mainly from estrogen deficiency. However, many women who received estrogen replacement therapy still lose bone with age and develop age--related osteoporotic fractures (albeit at a lower rate than those taking estrogens), indicating that both estrogens and androgens play important roles for bone health in both women and men. The simultaneous decreases in bone mass, muscle mass and muscle strength increase the risk of falls and especially of hip fractures in both men and women >65 years of age. In fact, one-third of all hip fractures occur in men. The androgen receptor (AR) belongs to the nuclear receptor superfamily and controls transcription in a ligand dependent manner (Brinkman, et al., Mechanisms of androgen receptor activation and function, J. Ster. Biochem. Mol. Biol. 69, 307-313, 1999). Upon androgen binding, AR binds directly to specific DNA sequences present in the promoter region of androgen responsive genes, termed androgen response elements (AREs), to stimulate transcription. Using ARE-dependent transcription as a criterion, agents that bind to AR and stimulate AREdependent transcription can be classified as agonists, and those that bind to AR and suppress ARE-dependent transcription are classified as antagonists. A number of natural or synthetic androgen agonists have been used for treatment of musculoskeletal or hematopoietic disorders and for hormone replacement therapy. In addition, AR antagonists, such as flutamide or bicalutamide, are used for treatment of prostate cancer. However, clinical use of these androgen agonists or antagonists have been limited because of undesirable effects, such as hirsutism and prostate enlargement for agonists, and bone loss, fracture, gynecomastia and sarcopenia for antagonists. It would be useful to have available androgens with tissue selective agonistic activity, which increase bone formation and muscle mass but do not induce the virilization. A number of studies provide the proof of principle that androgens are osteoanabolic in women and men. Anabolic steroids, such as nandrolone decanoate or stanozolol, have been shown to increase bone mass in postmenopausal women. Beneficial effects of androgens on bone in post-menopausal osteoporosis are well-documented in recent studies using combined testosterone and estrogen administration (Hofbauer, et al., Androgen effects on bone metabolism: recent progress and controversies, Eur. J. Endocrinol. 140, 271-286, 1999). Combined treatment increased significantly the rate and extent of the rise in BMD (lumbar and hip), relative to treatment with estrogen alone. Additionally, estrogen-progestin combinations that incorporate an androgenic progestin (norethindrone) rather than medroxyprogesterone acetate yielded greater improvements in hip BMD. These results have recently been confirmed in a larger (N=311) 2 year, double blind comparison study in which oral conjugated estrogen (CEE) and methyltestosterone combinations were demonstrated to be effective in promoting accrual of bone mass in the spine and hip, while conjugated estrogen therapy alone prevented bone loss (A twoyear, double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women: Effects on bone mineral density, symptoms and lipid profiles. J Reprod Med. 44(12):1012-20, 1999). Despite the beneficial effects of androgens in postmenopausal women, the use of androgens has been limited because of the undesirable virilizing and metabolic action of androgens. The data from Watts and colleagues demonstrate that hot flushes decrease in women treated with CEE+ methyltestosterone; however, 30% of these women suffered from significant increases in acne and facial hair, a complication of all current androgen pharmacotherapies (Watts, et al., Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause, Obstet. Gynecol. 85, 529-537, 1995). Moreover, the addition of methyltestosterone to CEE markedly decreased HDL levels, as seen in other studies. Thus, the current virilizing and metabolic side effect profile of androgen therapies provide a strong rationale for developing tissue selective androgen agonists for bone.
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Web site: http://www.delphion.com/details?pn=US06645974__ •
Benzimidazolone peptidometics as thrombin receptor antagonist Inventor(s): Maryanoff; Bruce E. (Forest Grove, PA), McComsey; David F. (Warminster, PA), White; Kimberly B. (North Wales, PA), Zhang; Han-Cheng (Lansdale, PA) Assignee(s): OrthoMcNeil Pharmaceutical, Inc. (Raritan, NJ) Patent Number: 6,630,451 Date filed: June 22, 2000 Abstract: The invention is directed to novel benzimidazolone peptidomimetic compounds which are useful as thrombin receptor antagonists for the treatment of diseases associated with thrombosis, restenosis, hypertension, heart failure, arrhythmia, inflammation, angina, stroke, atherosclerosis, ischemic conditions, Angiogenesis related disorders, cancer, and neurodegenerative disorders. Pharmaceutical compositions comprising the substituted benzimidazolone peptidomimetics of the present invention and methods of treating conditions mediated by the thrombin receptor are also disclosed. Excerpt(s): Thrombin is an important serine protease in hemostasis and thrombosis. One of the key actions of thrombin is cellular modulation via receptor activation. A functional human thrombin receptor (PAR-1), cloned by Coughlin in 1991 (T. -K. Vu, Cell 1991, 64, 1057), was found to be a member of the G-protein coupled receptor (GPCR) superfamily. The receptor activation putatively occurs by N-terminal recognition and proteolytic cleavage at the Arg-41/Ser-42 peptide bond to reveal a truncated N-terminus. This new N-terminus acting as a tethered ligand to recognize a site on the receptor, can trigger activation and signal transduction leading to platelet aggregation. Since 1991, three other protease-activated receptors with extensive homology to the thrombin receptor, "PAR-2" (S. Nystedt, Proc. Natl. Acad. Sci USA 1994, 91, 9208), "PAR-3" (H. Ishihara, Nature 1997, 386, 502), and "PAR-4" (W.-F. Xu, Proc. Natl. Acad. Sci USA 1998, 95, 6642), have been cloned. Thrombin receptor (PAR-1) specific antibody-induced blockade of the platelet thrombin receptor has shown efficacy against arterial thrombosis in vivo (J. J. Cook Circulation 1995, 91, 2961). Hence, antagonists of the thrombin receptor (PAR-1) are useful to block these proteaseactivated receptors and, as such, may be used to treat platelet mediated thrombotic disorders such as myocardial infarction, stroke, restenosis, angina, atherosclerosis, and ischemic conditions. The thrombin receptor (PAR-1) has also been identified on other cell types: endothelial, fibroblast, renal, osteosarcoma, smooth muscle, myocytes, tumor, and neuronal/glia. Thrombin activation of endothelial cells upregulates P-selectin to induce polymorphonuclear leukocyte adhesion--an inflammatory response of the vessel wall (Y. Sugama, J. Cell Biol. 1992, 119, 935). In fibroblasts, thrombin receptor (PAR-1) activation induces proliferation and transmission of mitogenic signals (D. T. Hung, J. Cell Biol. 1992, 116, 827). Thrombin has been implicated in osteoblast proliferation through its activation of osteoblast cells (D. N. Tatakis, Biochem. Biophys. Res. Commun. 1991, 174, 181). Thrombin has been implicated in the regulation and retraction of neurons (K. Jalink, J. Cell. Biol. 1992, 118, 411). Therefore, in this context, the antagonist compounds of this invention may also be useful against inflammation, osteoporosis, Angiogenesis related disorders, cancer, neurodegenerative disorders, hypertension, heart failure, arrhythmia, glomerulonephritis. The compounds of the present invention are a structurally novel class of benzimidazolone peptidomimetics represented by the general formula (I) below.
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Web site: http://www.delphion.com/details?pn=US06630451__ •
Benzopyrancarboxylic acid derivatives for the treatment of diabetes and lipid disorders Inventor(s): Boueres; Julia K. (Piscataway, NJ), Desai; Ranjit C. (Kendall Park, NJ), Koyama; Hiroo (Hoboken, NJ), Miller; Daniel J. (Edison, NJ), Sahoo; Soumya P. (Old Bridge, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,645,997 Date filed: September 24, 2001 Abstract: A class of benzopyrancarboxylic acid derivatives comprises compounds that are potent agonists of PPAR alpha and/or gamma, and are therefore useful in the treatment, control or prevention of non-insulin dependent diabetes mellitus (NIDDM), hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, obesity, vascular restenosis, inflammation, and other PPAR alpha and/or gamma mediated diseases, disorders and conditions. Excerpt(s): The instant invention is concerned with benzopyrancarboxylic acids and related heterocyclic compounds and pharmaceutically acceptable salts and prodrugs thereof which are useful as therapeutic compounds, particularly in the treatment and prevention of Type 2 diabetes mellitus, often referred to as non-insulin dependent diabetes (NIDDM), of conditions that are often associated with this disease, and of lipid disorders. Diabetes refers to a disease process derived from multiple causative factors and characterized by elevated levels of plasma glucose or hyperglycemia in the fasting state or after administration of glucose during an oral glucose tolerance test. Persistent or uncontrolled hyperglycemia is associated with increased and premature morbidity and mortality. Often abnormal glucose homeostasis is associated both directly and indirectly with alterations of the lipid, lipoprotein and apolipoprotein metabolism and other metabolic and hemodynamic disease. Therefore patients with Type 2 diabetes mellitus are at especially increased risk of macrovascular and microvascular complications, including coronary heart disease, stroke, peripheral vascular disease, hypertension, nephropathy, neuropathy, and retinopathy. Therefore, therapeutical control of glucose homeostasis, lipid metabolism and hypertension are critically important in the clinical management and treatment of diabetes mellitus. There are two generally recognized forms of diabetes. In type 1 diabetes, or insulin-dependent diabetes mellitus (IDDM), patients produce little or no insulin, the hormone which regulates glucose utilization. In type 2 diabetes, or noninsulin dependent diabetes mellitus (NIDDM), patients often have plasma insulin levels that are the same or even elevated compared to nondiabetic subjects; however, these patients have developed a resistance to the insulin stimulating effect on glucose and lipid metabolism in the main insulinsensitive tissues, which are muscle, liver and adipose tissues, and the plasma insulin levels, while elevated, are insufficient to overcome the pronounced insulin resistance. Web site: http://www.delphion.com/details?pn=US06645997__
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Benzyl compounds which inhibit leukocyte adhesion mediated by VLA-4 Inventor(s): Dappen; Michael S. (640 Topaz St., Redwood City, CA 94061), Dressen; Darren B. (3110 Casa De Campo #2, San Mateo, CA 94403), Grant; Francine S. (3735 Sacromento St., San Francisco, CA 94118), Konradi; Andrei W. (95 Cervantes #105, San Francisco, CA 94123), Lombardo; Louis John (412 S. Woods Rd., Belle Mead, NJ 08502), Pleiss; Michael A. (848 Stella Ct., Sunnyvale, CA 94087), Semko; Christopher M. (2361 Carpenter Ct., Fremont, CA 94539), Thorsett; Eugene D. (571 Buena Vista, Moss Beach, CA 94038) Assignee(s): none reported Patent Number: 6,586,602 Date filed: January 14, 2002 Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, wherein the disease may be, for example, asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis. Excerpt(s): This invention relates to compounds which inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. All of the above publications, patents and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety. Intercellular adhesion mediated by VLA-4 and other cell surface receptors is associated with a number of inflammatory responses. At the site of an injury or other inflammatory stimulus, activated vascular endothelial cells express molecules that are adhesive for leukocytes. The mechanics of leukocyte adhesion to endothelial cells involves, in part, the recognition and binding of cell surface receptors on leukocytes to the corresponding cell surface molecules on endothelial cells. Once bound, the leukocytes migrate across the blood vessel wall to enter the injured site and release chemical mediators to combat infection. For reviews of adhesion receptors of the immune system, see, for example, Springer.sup.3 and Osborn.sup.4. Web site: http://www.delphion.com/details?pn=US06586602__
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Breakers of advanced glycation endproducts Inventor(s): Rahbar; Samuel (Encino, CA) Assignee(s): City of Hope (Duarte, CA) Patent Number: 6,589,944 Date filed: July 27, 2000 Abstract: Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of a variety of debilitating diseases such as diabetes, atherosclerosis, Alzheimer's and rheumatoid arthritis, as well as in the normal aging process. Five compounds are here reported to be active in breaking AGE-protein cross-links. These compounds are L-bis-[4-(4-chlorobenzamido-phenoxyisobutyryl)cystine] (LR20); 4-(3,5-
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dichlorophenylureido)phenoxyisobutyryl-1-amido-cyclohexane-1-carbox ylic acid (LR23); methylene bis [4,4'-(2-chlorophenylureido-phenoxyisobutyric acid)] (LR90); 5arninosalicylic acid (5-ASA); and metformin. These compounds may be used to reverse the debilitating effects of those diseases in which AGEs are formed. Excerpt(s): Glucose and other reducing sugars react and bind covalently to proteins, lipoproteins and DNA by a process known as non-enzymatic glycation. Glucose latches onto tissue proteins by coupling its carbonyl group to a side-chain amino group such as that found on lysine. Over time, these adducts form structures called advanced glycation endproducts (AGEs) (protein-aging). These cross-linked proteins stiffen connective tissue and lead to tissue damage in the kidney, retina, vascular wall and nerves. The formation of AGEs on long-lived connective tissue accounts for the increase in collagen cross-linking that accompanies normal aging which occurs at an accelerated rate in diabetes. The publications and other materials used herein to illuminate the background of the invention or provide additional details respecting the practice, are incorporated by reference, and for convenience are respectively grouped in the appended List of References. Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of a variety of debilitating diseases such as diabetes, atherosclerosis, Alzheimer's and rheumatoid arthritis, as well as in the normal aging process. Most recent researchers confirm a significant role of the accumulation of AGE cross-links in promoting the decreased cardiovascular compliance of aging (Asif et al., 2000). The process of AGE formation on arterial wall matrix proteins may be related to the development of atherosclerosis in many different ways, such as generation of free radicals (ROS) during the glycation process, inhibition of a normal network formation in collagen by AGE accumulation (Brownlee, 1994), and increased adhesion of monocytes (Gilcrease and Hoover, 1992). Web site: http://www.delphion.com/details?pn=US06589944__ •
Combination therapy employing ileal bile acid transport inhibiting benzothipines and HMG Co-A reductase inhibitors Inventor(s): Glenn; Kevin C. (Maryland Heights, MO), Keller; Bradley T. (Chesterfield, MO), Manning; Robert E. (St. Louis, MO) Assignee(s): G.D. Searle & Co. (Chicago, IL) Patent Number: 6,642,268 Date filed: February 15, 2002 Abstract: Provided are novel benzothiepines, derivatives, and analogs thereof; pharmaceutical compositions containing them; and methods of using these compounds and compositions in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as those associated with atherosclerosis or hypercholesterolemia, in mammals. Also provided are compositions and methods for combination therapy employing ileal bile acid transport inhibitors and HMG Co--A reductase inhibitors for the treatment of hyperlipidemic conditions. Excerpt(s): The present invention relates to novel benzothiepines, derivatives and analogs thereof, in combination with HMG Co--A reductase inhibitors, pharmaceutical compositions containing them, and use of these compositions in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as is associated with atherosclerosis or hypercholesterolemia is mammals. It is well-settled that hyperlipidemic conditions associated with elevated concentrations of total cholesterol
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and low-density lipoprotein cholesterol are major risk factors for coronary heart disease and particularly atherosclerosis. Interfering with the circulation of bile acids within the lumen of the intestinal tract is found to reduce the levels of serum cholesterol is a causal relationship. Epidemiological data has accumulated which indicates such reduction leads to an improvement in the disease state of atherosclerosis. Stedronsky, in "Interaction of bile acids and cholesterol with nonsystemic agents having hypocholesterolemic properties," Biochimica et Biophysica Acta. 1210 (1994) 255-287 discusses the biochemistry, physiology and known active agents surrounding bile acids and cholesterol. Pathophysiologic alterations are shown to be consistent with interruption of the enterohepatic circulation of bile acids in humans by Heubi, J. E., et al. See "Primary Bile Acid Malabsorption: Defective in Vitro Ileal Active Bile Acid Transport", Gastroenterology, 1982:83:804-11. Web site: http://www.delphion.com/details?pn=US06642268__ •
Combinations of ileal bile acid transport inhibitors and fibric acid derivatives for cardiovascular indications Inventor(s): Glenn; Kevin C. (Maryland Heights, MO), Keller; Bradley T. (Chesterfield, MO), Schuh; Joseph R. (St. Louis, MO) Assignee(s): G.D. Searle, LLC (Chicago, IL) Patent Number: 6,638,969 Date filed: December 17, 1999 Abstract: The present invention provides combinations of cardiovascular therapeutic compounds for the prophylaxis or treatment of cardiovascular disease including hypercholesterolemia, atherosclerosis, or hyperlipidemia. Combinations disclosed include an ileal bile acid transport inhibitor combined with a fibric acid derivative. Excerpt(s): The present invention relates to methods of treating cardiovascular diseases, and specifically relates to combinations of compounds, compositions, and methods for their use in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as are associated with atherosclerosis, hypercholesterolemia, and other coronary artery disease in mammals. More particularly, the invention relates to ileal bile acid transporter (IBAT) inhibiting compounds. The invention also relates to fibric acid derivatives (fibrates). It is well-settled that hyperlipidemic conditions associated with elevated concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol are major risk factors for coronary heart disease and particularly atherosclerosis. Since high levels of LDL cholesterol increase the risk of atherosclerosis, methods for lowering plasma LDL cholesterol would be therapeutically beneficial for the treatment of atherosclerosis and other diseases associated with accumulation of lipid in the blood vessels. These diseases include, but are not limited to, coronary heart disease, peripheral vascular disease, and stroke. Atherosclerosis underlies most coronary artery disease (CAD), a major cause of morbidity and mortality in modern society. High LDL cholesterol (above about 180 mg/dl) and low HDL cholesterol (below 35 mg/dl) have been shown to be important contributors to the development of atherosclerosis. Other diseases or risk factors, such as peripheral vascular disease, stroke, and hypercholesterolemia are negatively affected by adverse HDL/LDL ratios. Web site: http://www.delphion.com/details?pn=US06638969__
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Compositions and methods for improving vascular health Inventor(s): Chevaux; Kati A. (Seattle, WA), Dombroski; Amy (Stanhope, NJ), Jerome; Ralph (Blairstown, NJ), Schmitz; Harold H. (Branchburg, NJ) Assignee(s): Mars, Incorporated (McLean, VA) Patent Number: 6,610,320 Date filed: April 10, 2001 Abstract: This invention relates to compositions containing polyphenols, for example, cocoa polyphenols such as procyanidins, in combination with at least one cholesterol lowering agent, and methods for improving vascular health including treating and preventing atherosclerosis and cardiovascular disease. Excerpt(s): This invention relates to compositions containing polyphenols, for example, cocoa polyphenols such as procyanidins in combination with at least one cholesterol lowering agent and methods for improving vascular health including treating and preventing atherosclerosis and cardiovascular disease. Coronary artery disease, the primary form of cardiovascular disease (CVD), is the major cause of death in the United States today. Cerebrovascular disease is the third. The etiology of both coronary artery and cerebrovascular diseases is attributed to atherosclerosis. Through its clinical manifestations, atherosclerosis is the major cause of the more than one million heart attacks, approximately 400,000 strokes that occur each year and numerous vascular circulation problems. Many patients suffer from hypertension. A substantial body of evidence has established a causal relationship between hypercholesterolemia and premature atherosclerosis; the higher the levels of plasma cholesterol, the greater the risk of subsequent heart attack. (see e.g. Steinberg, D., JAMA 264:3047 (1990)). In the chain of events leading to atherosclerosis, it is believed that the initiating event is the formation of "fatty streaks" in carotid, coronary, and cerebral arteries, and in the aorta. These lesions include fatty deposits of cholesterol and cholesteryl ester that are found principally within the smooth muscle cells and macrophages of the intimal layer. The migration and proliferation of vascular smooth muscle cells play a crucial role in the pathogenesis of atherosclerosis following the initial deposition of lipid. Web site: http://www.delphion.com/details?pn=US06610320__
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Crystalline [methyl(methylsulfonyl)amino]p acid]calcium salt
bis[(e)-7-[4-(4-fluorophenyl)-6-isopropyl-2yrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic
Inventor(s): Taylor; Nigel P (Macclesfield, GB) Assignee(s): Astrazeneca AB (Sodertalje, SE) Patent Number: 6,589,959 Date filed: June 28, 2001 Abstract: The present invention relates to a crystalline form of the compound bis[(E)-7[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]p yrimidin-5yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid]calcium salt, as well as processes for its manufacture and pharmaceutical compositions comprising the crystalline form, which is useful as an agent for treating hyperlipidemia, hypercholesterolemia and atherosclerosis.
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Excerpt(s): This application is the National Phase of International Application PCT/GB99/04439 filed Dec. 23, 1999 which designated the U.S. and that International Application was published under PCT Article 21(2) in English. The present invention relates to a novel crystalline chemical compound and more particularly to a novel crystalline form of bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2[methyl(methylsulfonyl)amino]p yrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid]calcium salt, hereinafter referred to as "the Agent", and illustrated in Formula I hereinafter, which compound is an inhibitor of the enzyme 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG CoA reductase) and is useful as a pharmaceutical agent, for example in the treatment of hyperlipidemia, hypercholesterolemia and atherosclerosis, as well as other diseases or conditions in which HMG CoA reductase is implicated. The invention also relates to processes for the manufacture of the crystalline form, pharmaceutical compositions comprising the crystalline form and the use of the crystalline form in medical treatment. European Patent Application, Publication No. 521471 (hereinafter EPA 521471), which is herein incorporated by reference, discloses an amorphous (powder) form of the Agent, prepared by dissolving the corresponding sodium salt in water, adding calcium chloride and collecting the resultant precipitate by filtration. Web site: http://www.delphion.com/details?pn=US06589959__ •
Dimer of molecular variant of apolipoprotein and processes for the production thereof Inventor(s): Abrahmsen; Lars (Stockholm, SE), Chmielewska; Joanna (Stockholm, SE), Franceschini; Guido (Milan, IT), Holmgren; Erik (Lidingo, SE), Lake; Mats (Lidingo, SE), Lind; Peter (Uppsala, SE), Nilsson; Bjorn (Sollentuna, SE), Sirtori; Cesare (Milan, IT) Assignee(s): Esperion Therapeutics, Inc. (Ann Arbor, MI) Patent Number: 6,617,134 Date filed: March 1, 1999 Abstract: Substantially pure dimers of Apolipoprotein AI-Milano (APO-AI-M/APO AIM) were isolated from plasma and characterized. Apolipoprotein AI-M dimer can also be produced in a recombinant Escherichia coli system. Pharmaceutical compositions comprising the ApoAI-AI-M/ApoAI-M are described. Patients with atherosclerosis or cardiovascular diseases can be treated with the dimer. Medicaments containing the dimer can also be used to prevent thrombosis in different clinical circumstances, both at the arterial and at the venous level. The dimer can also act as a prodrug for the monomer. Excerpt(s): The clear correlation between elevated levels of serum cholesterol and the development of coronary heart disease (CHD) has been repeatedly confirmed, based on epidemiological and longitudinal studies. The definition, however, of complex mechanisms of cholesterol transport in plasma, has allowed the recognition of a selective function of circulating lipoproteins in determining the risk for CHD. There are, in fact, four major circulating lipoproteins: chylomicrons (CM), very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins. While CM constitute a short-lived product of intestinal fat absorption, VLDL and, particularly, LDL are responsible for cholesterol transport into tissues, including for example the arterial walls. In contrast, HDL are directly involved in the removal of cholesterol from peripheral tissues, carrying it back either to the liver or to other lipoproteins, by a mechanism known as "reverse cholesterol transport" (RCT). The "protective" role of
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HDL has been confirmed in a number of studies (e.g. Miller et al. Lancet, 1977:965-968 and Whayne et al. Atherosclerosis 1981;39:411-419). In these, the elevated levels of LDL, less so of VLDL, seem to be clearly associated with an increased cardiovascular risk, whereas high HDL levels seem to confer cardiovascular protection. The protective role of HDL has been further strongly supported by the in vivo studies, showing that HDL infusions into rabbits may hinder the development of cholesterol induced arterial lesions (Badimon et al, Lab. Invest. 60, 455-61, 1989)) and/or induce regression of same (Badimon et al, J Clin Invest. 85, 1234-41, 1990). Web site: http://www.delphion.com/details?pn=US06617134__ •
Endothelial NOS transgenic animals and methods of use Inventor(s): Fishman; Mark C. (Newton Center, MA), Huang; Paul L. (Boston, MA), Moskowitz; Michael A. (Belmont, MA) Assignee(s): The General Hospital Corporation (Boston, MA) Patent Number: 6,630,347 Date filed: October 20, 2000 Abstract: This invention relates to transgenic non-human animals comprising a disrupted endothelial nitric oxide synthase gene. These animals exhibit abnormal wound-healing properties and hypertension. This invention also relates to methods of using the transgenic animals to screen for compounds having a potential therapeutic utility for vascular endothelial disorders, such as hypertension, cerebral ischemia or stroke, atherosclerosis and wound-healing activities. Moreover, this invention also relates to methods of treating a patient suffering from hypertension and wound-healing abnormalities with the compounds identified using the transgenic animals, and methods of making the transgenic animals. A method of treating a wound using nitroglycerin is also provided. Excerpt(s): Part of the work performed during the development of this invention was supported by U.S. Government funds. The U.S. Government may have certain rights in this invention. This invention relates to transgenic non-human animals comprising a disrupted endothelial nitric oxide synthase gene. This invention also relates to methods of using these transgenic animals to screen compounds for activity against vascular endothelial disorders such as hypertension, stroke, and atherosclerosis, as well as for wound healing activity; methods of treating a patient suffering from a vascular endothelial disorder; methods of making the transgenic animals; and cell lines comprising a disrupted eNOS gene. In 1980, Furchgott and Zawadzzi first proposed the existence of endothelium derived relaxing factor or EDRF, later identified as nitric oxide. Furchgott (1980); Furchgott (1988); Ignarro (1988); Palmer (1987). Nitric oxide is an important messenger molecule produced by endothelial cells, neurons, macrophages, and other tissues. Marietta (1989); Moncada (1991); Nathan (1992); Snyder (1992); and Dawson et al. (1992). Since nitric oxide is a gas with no known storage mechanism, it diffuses freely across membranes and is extremely labile. Nitric oxide has a biological half-life on the order of seconds. Web site: http://www.delphion.com/details?pn=US06630347__
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Fas ligand-like protein, its production and use Inventor(s): Hikichi; Yukiko (Tsukuba, JP), Nishi; Kazunori (Tsukuba, JP), Shintani; Yasushi (Tsukuba, JP) Assignee(s): Takeda Chemical Industries, Ltd. (Osaka, JP) Patent Number: 6,590,090 Date filed: August 31, 2000 Abstract: This invention relates to a Fas ligand-like protein having an apotosis-inducing actibvity, etc. or its salt, a partial peptide of the protein or its salt; a DNA coding for the protein; a recombinant vector; a transformant; a method for producing the protein, a pharmaceutical composition comprising the protein, the partial peptide or its salt; and an antibody to the protein or the partial peptide. The protein, the partial peptide or its salt, and the DNA are useful as a prophylactic or therapeutic agent for cancer, viral infection, Helicobacter pylori infection, invasive staphylococcia, hepatitis, nephritis, bone disease, atherosclerosis or pain. The antibody can be used in assay of the protein, the partial peptide or its salt. The protein, the partial peptide or its salt is useful as a reagent for the screening for candidate medical compounds. Excerpt(s): The present invention relates to a novel fas ligand-like protein having an apotosis-inducing activity, etc. and a DNA coding for the protein. A multicellular organism maintains its homeostasis ingeniously by controlling the proliferation and death of its cells. In the course of ontogenesis, many cells are eliminated through apotosis, and even in a mature organism the cells constituting its tissues maintain their functional integrity balancing proliferation against death. Cell death in this context is generally termed "programmed cell death", which is known to occur through the process of apotosis which is morphologically distinguished from that of necrosis, the accidental cell death caused by physical and chemical factors. Apoptotic cell death is characterized by blebbing of the cell membrane, chromatin condensation and DNA fragmentation, with the affected cells being eventually removed by phagocytic cells such as macrophages for reutilization (International Review of Cytology, 68, 251-306, 1980). Many physiological and pathological events related to apotosis have been identified until now and many attempts made to diagnose, prevent, or treat various diseases through induction or inhibition of the process of apotosis (Science, 267, 1456-1462, 1995). Apotosis is one of the vital phenomena which are attracting more than usual attention in the pharmaceutical industries. Web site: http://www.delphion.com/details?pn=US06590090__
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Functional assay of high-density lipoprotein Inventor(s): Fogelman; Alan M. (Beverly Hills, CA), Hama; Susan (Torrance, CA), Navab; Mohamad (Los Angeles, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,596,544 Date filed: March 31, 2000 Abstract: This invention provides novel assays that are prognostic and/or diagnostic for atherosclerosis or risk of atherosclerosis. It was discovered that high density lipoprotein (HDL) or components thereof can prevent the oxidation of lipids (e.g. lipids present in LDLs) and can also repair (reduce) already oxidized lipids and thereby
Patents 187
reduce the inflammatory response associated with and characteristic of atherosclerotic plaque formation. Moreover it was a discovery of this invention that individuals vary in the ability of their HDL to afford such protection. Thus an assay of HDL protective and/or repair activity provides a highly effective assay for risk of atherosclerosis and its associated pathologies and such assays are provided herein. Excerpt(s): This application is related to an application naming Fogelman et al. as inventors entitled "CONTROL OF A GENE INDUCED BY OXIDIZED LIPIDS IN HUMAN ARTERY WALL CELLS", filed on Mar. 31, 2000 which is incorporated herein by reference in its entirety for all purposes. Cardiovascular disease is a leading cause of morbidity and mortality, particularly in the United States and in Western European countries. Several causative factors are implicated in the development of cardiovascular disease including hereditary predisposition to the disease, gender, lifestyle factors such as smoking and diet, age, hypertension, and hyperlipidemia, including hypercholesterolemia. Several of these factors, particularly hyperlipidemia and hypercholesteremia (high blood cholesterol concentrations) provide a significant risk factor associated with atherosclerosis. Cholesterol is present in the blood as free and esterified cholesterol within lipoprotein particles, commonly known as chylomicrons, very low density lipoproteins (VLDLs), low density lipoproteins (LDLs), and high density lipoproteins (HDLs). Concentration of total cholesterol in the blood is influenced by (1) absorption of cholesterol from the digestive tract, (2) synthesis of cholesterol from dietary constituents such as carbohydrates, proteins, fats and ethanol, and (3) removal of cholesterol from blood by tissues, especially the liver, and subsequent conversion of the cholesterol to bile acids, steroid hormones, and biliary cholesterol. Web site: http://www.delphion.com/details?pn=US06596544__ •
Implant material Inventor(s): Campbell; Gordon Ronald (Brookfield, AU), Campbell; Julie Hazel (Brookfield, AU) Assignee(s): The University of Queeland of St. Lucia (AU) Patent Number: 6,626,823 Date filed: May 15, 2001 Abstract: Disclosed are tissue implant materials for use in grafting procedures. More particularly non-vascular tissue for use as vascular graft material and a method of vascular grafting using non-vascular tissue is disclosed. The tissue is preferably autologous relative to the recipient of the graft and is conveniently prepared around or on a molding support inserted into a body cavity of the intended recipient of the graft. These tissues and methods are particularly useful in the treatment or prophylaxis of diseased or damaged blood vessels such as in atherosclerosis. Excerpt(s): The present invention relates generally to tissue implant material for use in grafting procedures. More particularly, the present invention provides non-vascular tissue for use as vascular graft material. The present invention further contemplates a method of vascular grafting using non-vascular tissue. The tissue of the present invention is preferably autologous relative to the recipient of the graft and is conveniently prepared around or on a molding support inserted into a body cavity of the intended recipient of the graft. The tissues and methods of the present invention are particularly useful in the treatment or prophylaxis of diseased or damaged blood vessels such as in atherosclerosis. Throughout this specification, unless the context requires
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otherwise, the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers. Tissue grafting represents a major advance in the medical treatment of diseased or damaged tissue. In some cases, tissue grafting represents the sole avenue of medical treatment. However, the success of tissue grafting depends on a range of factors including the availability of suitable donor tissue and the extent of immunological intolerance by the recipient. Web site: http://www.delphion.com/details?pn=US06626823__ •
Irreversible inhibitors of tyrosine kinases Inventor(s): Bridges; Alexander James (Saline, MI), Denny; William Alexander (Auckland, NZ), Dobrusin; Ellen Myra (Ann Arbor, MI), Doherty; Annette Marian (Paris, FR), Fry; David William (Ypsilanti, MI), McNamara; Dennis Joseph (Ann Arbor, MI), Showalter; Howard Daniel Hollis (Ann Arbor, MI), Smaill; Jeffrey B. (Auckland, NZ), Zhou; Hairong (Ann Arbor, MI) Assignee(s): Warner-Lambert Company (Morris Plains, NJ) Patent Number: 6,602,863 Date filed: September 27, 2000 Abstract: The present invention provides compounds that are irreversible inhibitors of tyrosine kinases. Also provided is a method of treating cancer, restenosis, atherosclerosis, endometriosis, and psoriasis and a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases. Excerpt(s): This invention relates to compounds that are irreversible inhibitors of tyrosine kinases. This invention also relates to a method of treating cancer, atherosclerosis, restenosis, endometriosis, and psoriasis, and to a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases. Cancer has been viewed as a disease of the intracellular signalling system, or signal transduction mechanism. Cells receive instructions from many extracellular sources, instructing them to either proliferate or not to proliferate. The purpose of the signal transduction system is to receive these and other signals at the cell surface, get them into the cell, and then pass the signals on to the nucleus, the cytoskeleton, and transport and protein synthesis machinery. The most common cause of cancer is a series of defects, either in these proteins, when they are mutated, or in the regulation of the quantity of the protein in the cell such that it is over or under produced. Most often, there are key lesions in the cell which lead to a constitutive state whereby the cell nucleus receives a signal to proliferate, when this signal is not actually present. This can occur through a variety of mechanisms. Sometimes the cell may start to produce an authentic growth factor for its own receptors when it should not, the so-called autocrine loop mechanism. Mutations to the cell surface receptors, which usually signal into the cell by means of tyrosine kinases, can lead to activation of the kinase in the absence of ligand, and passing of a signal which is not really there. Alternatively, many surface kinases can be overexpressed on the cell surface leading to an inappropriately strong response to a weak signal. There are many levels inside the cell at which mutation or overexpression can lead to the same spurious signal arising in the cell, and there are many other kinds of signalling defects involved in cancer. This invention touches upon cancers which are driven by the three mechanisms just described, and which involve cell surface receptors of the epidermal growth factor receptor tyrosine kinase family (EGFR).
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This family consists of the EGF receptor (also known as Erb-B1), the Erb-B2 receptor, and its constitutively active oncoprotein mutant Neu, the Erb-B3 receptor and the ErbB4 receptor. Additionally, other biological processes driven through members of the EGF family of receptors can also be treated by compounds of the invention described below. Web site: http://www.delphion.com/details?pn=US06602863__ •
Low density lipoprotein binding proteins and their use in diagnosing and treating atherosclerosis Inventor(s): Arjona; Anibal A. (Boston, MA), Law; Simon W. (Lexington, MA), Lees; Ann M. (Brookline, MA), Lees; Robert S. (Brookline, MA) Assignee(s): Boston Heart Foundation, Inc. (Cambridge, MA) Patent Number: 6,605,588 Date filed: March 2, 2000 Abstract: Isolated polynucleotides encoding novel polypeptides which are capable of binding to native and methylated LDL (low density lipoprotein), the isolated polypeptides, called LBPs (LDL binding proteins), and biologically active fragments and analogs thereof, are described. Also described are methods for determining if an animal is at risk for atherosclerosis, methods for evaluating an agent for use in treating atherosclerosis, methods for treating atherosclerosis, and methods for treating a cell having an abnormality in structure or metabolism of LBP. Pharmaceutical compositions and vaccine compositions are also provided. Excerpt(s): Atherosclerosis is the principal cause of heart attacks and strokes. It has been reported that about 50% of all deaths in the United States, Europe and Japan are due to atherosclerosis. Atherosclerotic lesions in the arterial wall characterize atherosclerosis. Cholesteryl esters (CE) are present in these atherosclerotic lesions. Low density lipoprotein (LDL) has been shown to be the major carrier of plasma CE, and has been implicated as the agent by which CE enter the atherosclerotic lesions. Scattered groups of lipid-filled macrophages, called foam cells, are the first visible signs of atherosclerosis and are described as type I lesions. These macrophages are reported to contain CE derived from LDL. The macrophages recognize oxidized LDL, but not native LDL, and become foam cells by phagocytosing oxidized LDL. Larger, more organized collections of foam cells, fatty streaks, represent type II lesions. These lesions further develop into complex lesions called plaques, which can result in impeding the flow of blood in the artery. It is widely believed that accumulation of LDL in the artery depends on the presence of functionally modified endothelial cells in the arterial wall. It has been reported in animal models of atherosclerosis that LDL, both native LDL and methylated LDL, accumulates focally and irreversibly only at the edges of regenerating endothelial islands in aortic lesions, where functionally modified endothelial cells are present, but not in the centers of these islands where endothelial regeneration is completed. Similarly, LDL accumulates in human atherosclerotic lesions. The mechanism by which the LDL accumulates focally and irreversibly in arterial lesions has not heretofore been understood. Web site: http://www.delphion.com/details?pn=US06605588__
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Method for preventing, stabilizing or causing regression of atherosclerosis employing a combination of a cholesterol lowering drug and an ace inhibitor Inventor(s): Bergey; James L. (Lansdale, PA), Kawano; James C. (Narberth, PA), Tschollar; Werner (Lawrenceville, NJ), Yonce; Cary S. (Newtown, PA) Assignee(s): E.R. Squibb & Sons, Inc. (Princeton, NJ) Patent Number: 6,630,502 Date filed: December 2, 1991 Abstract: A method is provided for slowing the progression of atherosclerosis in hypertensive or normotensive patients and reducing or eliminating atherosclerotic lesions in such patients by administering a combination of a cholesterol lowering drug such as pravastatin, and an ACE inhibitor, especially one containing a mercapto moiety, such as captopril or zofenopril. Excerpt(s): The present invention relates to a method for preventing, stabilizing or causing regression of atherosclerosis in mammalian species by administering a combination of a cholesterol lowering drug, such as an HMG CoA reductase inhibitor, for example, pravastatin, and an ACE inhibitor, preferably an ACE inhibitor containing a mercapto moiety, such as captopril or zofenopril, and to a pharmaceutical combination for use in such method. The proatherosclerotic effect of elevated serum cholesterol on vascular tissue is well documented (Weinstein and Heider, "Protective action of calcium channel antagonists in atherogenesis and vascular injury," Am. J. Hypertens. 2: 20512,1989). It is also well known that platelets which may participate in the atherogenic process do so via mediators released upon activation (thromboxane A.sub.2 (TXA.sub.2), platelet aggregating factor (PAF), etc.,) which in turn stimulate smooth muscle cells to contract as well as to proliferate. The latter effect is an important step in atherosclerotic plaque formation (Hoak, "Platelets and atherosclerosis," Semin. Thromb. Hemost. 14: 202-5, 1988). Many of the stimulatory effects of prostanoids on vascular smooth muscle can be reversed by endothelium derived relaxing factor (EDRF), a substance whose metabolic stability and/or efficacy appears to be enhanced by captopril (Goldschmidt and Tallarida, "Effect of captopril exposure on endotheliumdependent relaxation in rabbit aorta," F.A.S.E.B. Journal 3: A1195, 1989). Web site: http://www.delphion.com/details?pn=US06630502__
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Method for the prediction of preeclampsia and other diseases Inventor(s): Arbogast; Bradley W. (Johnson City, TN) Assignee(s): Arbogast Pharmaceuticals, Inc. (Johnson City, TN) Patent Number: 6,642,055 Date filed: March 31, 2000 Abstract: The invention disclosed is a process for determining the cytoprotective activity of plasma that prevents the destruction of endothelial cells and forestalls the development of a number of diseases such as atherosclerosis, preeclampsia, edema, nephrotic syndrome, and stroke. The present invention includes a method of diagnosing a patient's proclivity to develop a disease having a correlation to a reduction in the concentration of pI 5.6 albumin in the plasma by determining a value indicative of the concentration of the pI 5.6 albumin that is not bound to VLDL ("free pI 5.6 albumin") in the patient's blood serum. The preferred embodiment of the process utilizes in vitro
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methods to obtain an indicator of the free pI 5.6 albumin instead of directly measuring the concentration of the free pI 5.6 albumin. The preferred method comprises the steps of:(a) providing a plasma sample containing free albumin, triglycerides, very low density lipoproteins, low density lipoproteins, and non-esterified fatty acids bound to the free albumin;(b) determining the concentration of the free albumin;(c) determining the concentration of the non-esterified fatty acids bound to the free albumin; and(d) calculating a value indicative of the toxicity preventing ability of the plasma by comparing the concentration of the free albumin to the concentration of the nonesterified fatty acids bound to the free albumin. The present process does not provide direct measurement of the cytoprotective activity of plasma, but rather, an empirical value which has clinical relevance in identifying patients with a high chance of developing diseases inhibited by pI 5.6 albumin. Excerpt(s): The present invention relates to methods for predicting and following illnesses. More particularly, the present invention relates to the diagnosis of preeclampsia and other diseases. Vascular disease is often related to the composition of blood flowing therethrough. In particular, high concentrations of very low density lipoproteins (VLDL) in blood have a deleterious effect on vascular integrity. Very low density lipoproteins in blood tend to break down the inner vascular walls causing vascular diseases including preeclampsia, atherosclerosis, stroke, peripheral vascular disease, diabetic vascular disease, and such. Methods providing earlier detection of vascular diseases, and methods for diagnosing a patient's proclivity toward developing a vascular disease at a later point in his life are desirable so that such disease may be better controlled, or even avoided. The early detection of preeclampsia is particularly important. Web site: http://www.delphion.com/details?pn=US06642055__ •
Method for the synthesis of compounds of formula I and their uses thereof Inventor(s): Avor; Kwasi S. (High Point, NC), Gopalaswamy; Ramesh (Greensboro, NC), Mjalli; Adnan M. M. (Jamestown, NC), Patron; Andrew (San Diego, CA), Wysong; Christopher L. (Winston-Salem, NC) Assignee(s): TransTech Pharma, Inc. (High Point, NC) Patent Number: 6,613,801 Date filed: March 5, 2001 Abstract: This invention provides certain compounds, methods of their preparation, pharmaceutical compositions comprising the compounds, their use in treating human or animal disorders. The compounds of the invention are useful as modulators of the interaction between the receptor for advanced glycated end products (RAGE) and its ligands, such as advanced glycated end products (AGEs), S100/calgranulin/ENRAGE,.beta.-amyloid and amphoterin, and for the management, treatment, control, or as an adjunct treatment for diseases in humans caused by RAGE. Such diseases or disease states include acute and chronic inflammation, the development of diabetic late complications such as increased vascular permeability, nephropathy, atherosclerosis, and retinopathy, the development of Alzheimer's disease, erectile dysfunction, and tumor invasion and metastasis. Excerpt(s): This invention relates to compounds which are modulators of the receptor for advanced glycated end products (RAGE) and interaction with its ligands such as advanced glycated end products (AGEs), S100/calgranulin/EN-RAGE,.beta.-amyloid
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and amphoterin, for the management, treatment, control, or as an adjunct treatment of diseases caused by RAGE. Incubation of proteins or lipids with aldose sugars results in nonenzymatic glycation and oxidation of amino groups on proteins to form Amadori adducts. Over time, the adducts undergo additional rearrangements, dehydrations, and cross-linking with other proteins to form complexes known as Advanced Glycosylation End Products (AGEs). Factors which promote formation of AGEs included delayed protein turnover (e.g. as in amyloidoses), accumulation of macromolecules having high lysine content, and high blood glucose levels (e.g. as in diabetes) (Hori et al., J. Biol. Chem. 270: 25752-761, (1995)). AGEs have implicated in a variety of disorders including complications associated with diabetes and normal aging. In addition to AGEs, other compounds can bind to, and modulate RAGE. In normal development, RAGE interacts with amphoterin, a polypeptide which mediates neurite outgrowth in cultured embryonic neurons (Hori et al., 1995). RAGE has also been shown to interact with ENRAGE, a protein having substantial similarity to calgranulin (Hofmann et al., Cell 97:889-901 (1999)). RAGE has also been shown to interact with.beta.-amyloid (Yan et al., Nature 389:589-595, (1997); Yan et al., Nature 382:685-691 (1996); Yan et al., Proc. Natl.Acad. Sci., 94:5296-5301 (1997)). Web site: http://www.delphion.com/details?pn=US06613801__ •
Methods of modulating lipid metabolism and storage Inventor(s): Burkly; Linda (West Newton, MA), Wang; Li Chun (North Grafton, MA) Assignee(s): Curis, Inc. (Cambridge, MA) Patent Number: 6,616,926 Date filed: November 2, 2000 Abstract: Anti-hedgehog antibodies directed at blocking the binding of hedgehog to its receptor patched-1, will impair lipid metabolism and storage. This invention presents methods for the treatment of a variety of lipid metabolism and lipid storage disorders, aberrant apolipoprotein expression, atherosclerosis and other lipid associated disorders using lipid modulators such as hedgehog antagonists or hedgehog agonists. Excerpt(s): This invention relates generally to methods for modulating the metabolism and storage of lipids. The invention relates particularly to the use of lipid metabolism and storage modulators such as agonists or antagonists of hedgehog activity to alter the metabolism of lipids in the gastrointestinal tract, as well as to alter the storage of lipids in gut epithelial tissue. Pathological conditions that affect storage, breakdown and intestinal absorption of lipids are included in a broad category of so-called "lipid metabolism disorders," and there are a variety of disorders that have been diagnosed. These include: diet-induced and regular hypercholesterolemia (Farese et al. Proc. Natl. Acad. Sci. USA 1995 92:1774-1778), abetalipoproteinemia and hypobetalipoproteinemia (Linton et al. J. Lipid Res.1993 34:521-541.) Several other lipid metabolism disorders of unknown origin have also been identified including Anderson's disease (Anderson et al. Med. J. Aust. 1961 11:617-621), and atherosclerosis (Purcell-Huynh et al. J. Clin. Invest. 1995 95:2246-2257.) General symptoms of lipid metabolism disorders include, but are not limited to, chronic diarrhea, inadequate weight gain or weight loss, inability to lose excess weight and general failure to thrive. (Case 35-1999, New England Journal of Medicine; 327: 628-635 1992.) The various lipid metabolism disorders have been thought to originate through aberrant expression of apolipoproteins and/or regulation of genes responsible for various aspects of lipid metabolism. The various lipid metabolism disorders are also thought to originate via malfunctions in embryonic tissue
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development. The generation of the intestines from the embryonic gut material depends solely on intercellular signaling between endodermal and mesodermal cells of the gut. It has been widely recognized that the hedgehog-signaling pathway plays a critical role in the direction of specialized mesoderm differentiation in the intestine and pancreas. (Apelqvist et al. Current Biology 1997 7:801-804.) Hedgehog is initially expressed in mouse embryos in the ventral part of the foregut endoderm, and has been shown to mediate endodermally derived signals in embryonic hindgut. (Id.) Specifically, mice with targeted deletion of hedgehog have evident foregut defects that are apparent as early as embryonic day 9.5, when the tracheal diverticulum begins to outgrow, suggesting that hedgehog and its signaling components are involved in foregut defects in humans. (Litingtung et al. Nature Genetics 1998 20:58-60.) See also Yang et al. Molecular Medicine 1997 3:826-835. Web site: http://www.delphion.com/details?pn=US06616926__ •
Methods of using pomegranate extracts for causing regression in lesions due to arteriosclerosis in humans Inventor(s): Aviram; Michael (Kiriat-Haim, IL), Dornfeld; Leslie (Los Angeles, CA) Assignee(s): Stewart and Lynda Resnick Revocable Trust (Los Angeles, CA) Patent Number: 6,641,850 Date filed: November 19, 2001 Abstract: Methods of using pomegranate extracts of the present invention for treating patients with atherosclerosis, or increased intima-media thickness of an artery, are provided. The methods comprise the step of administering to the patient a composition comprising a therapeutically effective amount of an extract from pomegranate. The methods of the present invention may also be used to decrease the incidence of stroke or heart attack in a patient. Excerpt(s): The invention relates generally to pomegranate extracts and methods of using thereof, and specifically to methods of using pomegranate extracts for causing regression in lesions due to arteriosclerosis in humans. Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citation for these references may be found at the end of this application, preceding the claims. Oxidative stress, a major contributor to cardiovascular diseases (1), is associated with lipid peroxidation in arterial macrophages and in lipoproteins (1-3). Oxidized lowdensity lipoprotein (Ox-LDL) was shown to be atherogenic (2-4), thus, interventions to inhibit LDL oxidation by dietary antioxidants (4, 5) is of major importance to attenuate atherosclerosis. It was recently shown that vitamin E supplementation to patients with carotid artery stenosis inhibited LDL accumulation in arterial macrophages (6). Protection of lipids from oxidation can be also achieved by serum paraoxonase (PON1, an HDL-associated esterase that can hydrolyze and reduce specific lipid peroxides in arterial cells and lipoproteins in coronary and carotid lesions (7-10). Web site: http://www.delphion.com/details?pn=US06641850__
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Molecularly imprinted polymers for the treatment and diagnosis of medical conditions Inventor(s): Green; Bernard S. (Kibbutz Yavne, IL), Priwler; Morris (Modi'in, IL) Assignee(s): Semorex Inc. (North Brunswick, NJ) Patent Number: 6,638,498 Date filed: June 29, 2001 Abstract: Improved molecularly imprinted polymers (MIPs) with both higher and more specific binding capacity for particular bile acids and/or salts, including the synthesis of such MIPs, the compounds themselves, and specific applications thereof. As an example of a particularly preferred specific application of these compounds, the present invention encompasses the use of the MIPs as sequestrants in the gastrointestinal tract, particularly in order to bind and therefore remove toxins from the gastrointestinal tract. In addition, the present invention is also useful for treatment of various diseases which are related to, and/or characterized by, an effect of bile acids and salts, such as atherosclerosis, liver disease and various diseases of the gastrointestinal tract. The MIP compounds of the present invention are also useful for combination therapy with other medications and for diagnosis and monitoring of diseases. Excerpt(s): The present invention is related to novel molecularly imprinted polymers, and in particular to improvements in the production of molecularly imprinted polymers (MIPs), as well as to these specific MIPs, and to the use of MIPs for specific applications. The MIPs of the present invention are particularly suitable for binding to, and thereby removing, toxins in the gastrointestinal tract. As an exemplary implementation, the present invention is described with regard to the removal of bile acids and bile salts from the gastrointestinal tract. In addition, the present invention is also useful for treatment of various diseases which are related to, and/or characterized by an effect of, bile acids and bile salts, such as atherosclerosis, cancer, liver disease and various diseases of the gastrointestinal tract. The MIP compounds of the present invention are also useful for combination therapy with other medications. These medications may involve mechanisms of action that lower or change the composition of bile acids and salts in the body or by a different mechanism. In addition the present invention also is useful for the diagnosis and monitoring of various diseases by selectively binding to an established marker which is then identified using known binding indicator techniques such as fluorescence. As an illustrative example for implementation, the present invention is described with regard to the diagnosis of medical conditions which are related to, and or characterized by an effect of, bile acids and/or bile salts, such as atherosclerosis, various diseases of the gastrointestinal tract, cancer and inflammatory conditions. This is achieved by determining the level of at least one specific bile acid or salt or the ratio of at least one specific bile acid or to at least a second specific bile acid or salt and determining whether these levels fall within an establish range which indicates the potential existence of the relevant disease. The analysis is performed on bile acids and or bile salts found in serum, bile, gastric contents, and feces. The subject of molecularly imprinted polymers has been extensively reviewed (e.g., G. Wulff, Angew. Chem., Int. Ed. Engl. 1995, 34, 1812-1832; A. G. Mayyes and K. Mosbach, Trends Anal. Chem. 1997, 16, 321-332; E. N. Vulfson, C. Alexander, and M. J. Whitcombe Chem. Brit. 1997, 33, 23-26; K. Haupt and K. Mosbach, Trends Biotechnol. 1998, 16, 468-475; Molecular and Ionic Recognition with Imprinted Polymers, ACS Symp. Ser. 703; R. A. Bartsch and M. Maeda, Eds.; American Chemical Society, Washington, D.C., 1998) and a number of patents on this topic have been issued [e.g., U.S. Pat. No. 4,127,730 (Wulff, G., Sarhan A.); U.S. Pat. No. 5,110,833 (Mosbach. K.); U.S. Pat. No. 5,630,978 (Domb, A.,);
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U.S. Pat. No. 5,587,273 (Yan, M. et al.); U.S. Pat. No. 5,872,198 (Mosbach, K. et al;)]. A schematic depiction of the formation of MIPs for deoxycholic acid (DCA) and glycodeoxycholic acid (GDCA) is shown in FIGS. 1A and 1B. Although the binding/recognition site is actually a family of non-homogeneous sites, the scheme illustrates how the cavities for two similar substances may differ. The synthesis of MIPs, including those described with regard to the present invention in the "Description of the Preferred Embodiments" below, is performed with functional monomers. The monomers which were used for the present invention include all of the monomers listed in the following section. The synthesis of these monomers and related derivatives and analogs can be performed by organic chemists of ordinary skill in the art. It should be noted that although the present invention is described with regard to MIPs which bind bile acids and bile salts, this is for the purposes of description only and is not intended to be limiting in any way. Web site: http://www.delphion.com/details?pn=US06638498__ •
PARP inhibitors, pharmaceutical compositions comprising same, and methods of using same Inventor(s): Jackson; Paul F. (Bel Air, MD), Li; Jia-He (Cockeysville, MD), Maclin; Keith M. (Baltimore, MD), Zhang; Jie (Ellicott City, MD) Assignee(s): Guilford Pharmaceuticals Inc. (Baltimore, MD) Patent Number: 6,635,642 Date filed: September 1, 1998 Abstract: The present invention relates to PARP inhibitors, pharmaceutical compositions comprising the same, and methods of using the same to treat tissue damage resulting from cell damage or death due to necrosis or apoptosis, effect neuronal activities not mediated by NMDA toxicity; to treat neural tissue damage resulting from ischemia and reperfusion injury, neurological disorders and neurodegenerative diseases; to prevent or treat vascular stroke; to treat or prevent cardiovascular disorders; to treat other conditions and/or disorders such as age-related macular degeneration, AIDS and other immune senescence diseases, arthritis, atherosclerosis, cachexia, cancer, degenerative diseases of skeletal muscle involving replicative senescence, diabetes, head trauma, immune senescence, inflammatory bowel disorders (such as colitis and Crohn's disease), muscular dystrophy, osteoarthritis, osteoporosis, chronic and/or acute pain (such as neuropathic pain), renal failure, retinal ischemia, septic shock (such as endotoxic shock), organ damage due to transplantation, and skin aging; to extend the lifespan and proliferative capacity of cells; to alter gene expression of senescent cells; or to radiosensitize hypoxic tumor cells. Excerpt(s): The present invention relates to inhibitors of the nucleic enzyme poly(adenosine 5'-diphospho-ribose) polymerase ["poly(ADP-ribose) polymerase" or "PARP", which is also sometimes called "PARS" for poly(ADP-ribose) synthetase]. More particularly, the invention relates to the use of PARP inhibitors to prevent and/or treat tissue damage resulting from cell damage or death due to necrosis or apoptosis; neural tissue damage resulting from ischemia and reperfusion injury; neurological disorders and neurodegenerative diseases; to prevent or treat vascular stroke; to treat or prevent cardiovascular disorders; to treat other conditions and/or disorders such as age-related macular degeneration, AIDS and other immune senescence diseases, arthritis, atherosclerosis, cachexia, cancer, degenerative diseases of skeletal muscle involving replicative senescence, diabetes, head trauma, immune senescence, inflammatory bowel
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disorders (such as colitis and Crohn's disease), muscular dystrophy, osteoarthritis, osteoporosis, chronic and acute pain (such as neuropathic pain), renal failure, retinal ischemia, septic shock (such as endotoxic shock), and skin aging; to extend the lifespan and proliferative capacity of cells; to alter gene expression of senescent cells; or to radiosensitize hypoxic tumor cells. Poly(ADP-ribose) polymerase ("PARP") is an enzyme located in the nuclei of cells of various organs, including muscle, heart and brain cells. PARP plays a physiological role in the repair of strand breaks in DNA. Once activated by damaged DNA fragments, PARP catalyzes the attachment of up to 100 ADP-ribose units to a variety of nuclear proteins, including histones and PARP itself. While the exact range of functions of PARP has not been fully established, this enzyme is thought to play a role in enhancing DNA repair. During major cellular stresses, however, the extensive activation of PARP can rapidly lead to cell damage or death through depletion of energy stores. Four molecules of ATP are consumed for every molecule of NAD (the source of ADP-ribose) regenerated. Thus, NAD, the substrate of PARP, is depleted by massive PARP activation and, in the efforts to re-synthesize NAD, ATP may also be depleted. Web site: http://www.delphion.com/details?pn=US06635642__ •
Tyrosine kinase inhibitors Inventor(s): Bilodeau; Mark T. (Lansdale, PA), Hartman; George D. (Lansdale, PA), Hungate; Randall W. (Newbury Park, CA), Manley; Peter J. (Harleysville, PA), Rodman; Leonard (New York, NY) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,586,423 Date filed: February 1, 2002 Excerpt(s): The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals. Tyrosine kinases are a class of enzymes that catalyze the transfer of the terminal phosphate of adenosine triphosphate to tyrosine residues in protein substrates. Tyrosine kinases are believed, by way of substrate phosphorylation, to play critical roles in signal transduction for a number of cell functions. Though the exact mechanisms of signal transduction is still unclear, tyrosine kinases have been shown to be important contributing factors in cell proliferation, carcinogenesis and cell differentiation. Tyrosine kinases can be categorized as receptor type or non-receptor type. Receptor type tyrosine kinases have an extracellular, a transmembrane, and an intracellular portion, while nonreceptor type tyrosine kinases are wholly intracellular. Web site: http://www.delphion.com/details?pn=US06586423__
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Use of lecithin-cholesterol acyltransferase (LCAT) to reduce accumulation of cholesterol Inventor(s): Brewer, Jr.; H. Bryan (Rockville, MD), Hoeg; Jeffrey M. (Potomac, MD), Santamarina-Fojo; Silvia (Potomac, MD) Assignee(s): The United States of America as represented by the Department of Health and (Washington, DC) Patent Number: 6,635,614 Date filed: November 22, 1999 Abstract: This invention provides methods for treating atherosclerosis in a mammalian subject by increasing the activity of LCAT in the serum of the subject to a level effective to decrease the accumulation of cholesterol in the subject. Pharmaceutical dosage forms containing LCAT also are provided. Excerpt(s): This invention relates to methods for the prophylactic and therapeutic treatment of atherosclerosis and to diseases relating to a deficiency in lecithincholesterol acyltransferase activity. Atherosclerosis is a pathological condition of mammals characterized by the accumulation of cholesterol in the arteries. Cholesterol accumulates in the foam cells of the arterial wall, thereby narrowing the lumen. This results in decreased flow of blood. The clinical sequelae of atherosclerosis include heart disease and heart attack, stroke, and peripheral vascular disease. Together, these diseases account for more disease-related deaths in industrialized countries than any other cause. The development of human atherosclerosis is inversely related to the concentration of high density lipoproteins (HDL) in the serum. D. J. Gordon and B. M. Rifkind (1989) N. Engi. J. Med. 321:1311. High concentrations of HDL appear to protect against the development of premature atherosclerosis, while low HDL cholesterol concentrations are associated with an increased risk of cardiovascular disease. D. J. Gordon et al. (1986) Circulation 74:1217. It has been proposed that a 1% increase in the concentration of HDL would lead to a 3% reduction in risk for developing clinical atherosclerosis in man. Gordon and Rifkind, supra. Web site: http://www.delphion.com/details?pn=US06635614__
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Use of saw palmetto to prevent atherosclerosis Inventor(s): Goldberg; Michael E. (20 Aspen Dr., Ivyland, PA 18974), Weisman; Kenneth (30 Springton Pointe Dr., Newtown Square, PA 19073) Assignee(s): none reported Patent Number: 6,627,227 Date filed: May 8, 2001 Abstract: A method of decreasing atherosclerosis and its complications including but not limited to myocardial infarction, stroke, and peripheral vascular disease comprising administering to a human or animal an amount of saw palmetto or Permixon containing saw palmetto sufficient to decrease atherosclerosis and its complications. Excerpt(s): There are many steps in the biosynthesis and utilization by the tissues of testosterone. Testosterone is made mostly in the testicles. A lesser amount is made in the adrenals. Production is stimulated by secretion of GnRH or LHRH by the brain, which causes secretion of luteinizing hormone (LH) by the pituitary, which causes the testicles to make testosterone. Testosterone then flows into the blood stream and is absorbed by
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the target cells. Here it binds to a receptor and is transported into the cell and converted to dihydrotestosterone. This is bound and carried to the nucleus of the cell where it redirects cellular activity by turning on and off DNA. Hormonal manipulation is a term which refers to the reduction of testosterone or its effects by blocking any step in the above process in order to gain a desired effect. Until now the uses of hormonal manipulation include for example treating prostatic carcinoma, and treatment for baldness. For instance, leuprolide acetate is one of the compounds we previously discovered being effective in the prevention of such cardiac events. Leuprolide acetate is a synthetic nonapeptide of naturally occurring gonadotropin-releasing hormone (GnRH or LH-RH), the chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-Ltyrosyl-D-leucyl-L-leucyl -L-arginyl-N-ethyl-L-prolinamide acetate salt sold under the trade name Lupron or Lupron Depot, as identified by U.S. Pat. No. 4,897,256, the entire disclosure in incorporated by reference herein, is known for use in the treatment of prostatic carcinoma. Leuprolide is known to decrease levels of LHRH, LH and Testosterone (a sex hormone). Another compound we previously discovered as being effective in the prevention of such cardiac events is Goserelin acetate. Goserelin Acetate is a synthetic decapeptide analogue of LHRH or GnRH, is chemically described as an acetate salt of [D-Ser(Bu.sup.t).sup.6 Azygly.sup.10] LHRH. Its chemical structure is pyro-Glu-His-Trp-Ser-Tyr-D-Ser(Bu.sup.t)-Leu-Arg-Pro-Azgly-NH2 acetate [C59H84N18014 (C2H4O2) sold under the trademark Zoladex, as identified by the U.S. Pat. No. 5,510,460, the entire disclosure is incorporated by reference herein, is known for the use in treatment of prostatic carcinoma. Goserelin acetate is known to reduce levels of GnRH or LHRH, and Testosterone, a sex hormone. Web site: http://www.delphion.com/details?pn=US06627227__
Patent Applications on Atherosclerosis As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to atherosclerosis: •
2-substituted thiazolidinones as beta-3 adrenergic receptor agonists Inventor(s): Hu, Baihua; (Audubon, PA) Correspondence: WYETH; PATENT LAW GROUP; FIVE GIRALDA FARMS; MADISON; NJ; 07940; US Patent Application Number: 20030176412 Date filed: May 19, 2003 Abstract: This invention provides compounds of Formula I having the structure 1wherein:A, X, Y, Z, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are as defined hereinbefore or a pharmaceutically acceptable salt thereof, which are useful in treating or inhibiting metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, and frequent urination; and are particularly useful in the treatment or inhibition of type II diabetes.
10
This has been a common practice outside the United States prior to December 2000.
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Excerpt(s): This application is a divisional of U.S. application Ser. No. 10/132,483, filed Apr. 25, 2002, pending, which is a divisional of U.S. application Ser. No. 09/904,157, filed Jul. 12, 2001, now U.S. Pat. No. 6,410,734. The '157 application claims the benefit of U.S. Provisional Application No. 60/218,724, filed Jul. 17, 2000. This invention relates to 2-substituted thiazolidinone derivatives which are.beta.sub.3 adrenergic receptor agonists useful for the treatment of metabolic disorders related to insulin resistance or hyperglycemia (typically associated with obesity or glucose intolerance), atherosclerosis, gastrointestinal disorders, neurogenetic inflammation, and frequent urination, and are particularly useful in the treatment or inhibition of type II diabetes. The subdivision of.beta. adrenergic receptors (.beta.-AR) into.beta.sub.1- and.beta.sub.2AR has led to the development of.beta.sub.1- and.beta.sub.2-antagonists and/or agonists which have been useful for the treatment of cardiovascular disease and asthma. The recent discovery of "atypical" receptors, later called.beta.sub.3-AR, has led to the development of.beta.sub.3-AR agnoists which may be potentially useful as antiobesity and antidiabetic agents. For recent reviews on.beta.sub.3-AR agnoists , see: 1. A. D. Strosberg, Annu. Rev. Pharmacol. Toxicol. 1997, 37,421; 2. A. E. Weber, Ann. Rep. Med. Chem. 1998, 33, 193; 3. C. P. Kordik and A. B. Reitz, J. Med. Chem. 1999, 42, 181; 4. C. Weyer, J. F. Gautier and E. Danforth, Diabetes and Metabolism, 1999, 25, 11. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
2-Thia-1,6,8-Triaza-Naphthalene-2,2-Dioxides are kinase inhibitors Inventor(s): Repine, Joseph Thomas; (Ann Arbor, MI) Correspondence: WARNER-LAMBERT COMPANY; 2800 PLYMOUTH RD; ANN ARBOR; MI; 48105; US Patent Application Number: 20030186973 Date filed: January 21, 2003 Abstract: The present invention provides 2-thia-1,6,8-triaza-naphthalene-2,2-dioxide inhibitors of cyclin-dependent kinases, uses thereof and pharmaceutical compositions thereof.These compounds are useful for treating cell proliferative disorders, such as cancer, atherosclerosis, and restenosis. These compounds are potent inhibitors of kinases such as cyclin-dependent (cdks) and growth factor-mediated kinases.The present invention also provides a method of treating cell proliferative disorders 1 Excerpt(s): This invention relates to 2-Thia-1,6,8-Triaza-Naphthalene-2,2-Dioxi- des as inhibitors of kinases, particularly cyclin-dependent kinases. The compounds of the invention are useful for the treatment of inflammation, cell proliferative diseases such as cancer and restenosis, and neurodegenerative diseases such as Alzheimer's disease. Cyclin-dependent kinases and related serine/threonine protein kinases are important cellular enzymes that perform essential functions in regulating cell division and proliferation. The cyclin-dependent kinase catalytic units, of which nine have now been described, are activated by regulatory subunits known as cyclins. At least 16 mammalian cyclins have been identified (Johnson, D. G. & Walker, C. L. Annu. Rev. Pharmacol. Toxicol 1999, 39, 295-312). Cyclin D/Cdk4, Cyclin D/Cdk6, CyclinB/Cdk1, Cyclin A/cdk2 and Cyclin E/cdk2 are all important regulators of cell cycle progression. Other functions of cyclin/Cdk heterodimers include regulation of transcription, DNA repair, differentiation and apoptosis. Increased activity or temporally abnormal activation of certain of these kinases has been shown to result in the development of human tumors and other proliferative disorders such as restenosis. Indeed, human tumor development is commonly associated with alterations in either the Cdk proteins
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themselves or their regulators (Cordon-Cardo, C. Am. J. Pathol. 1995, 147, 545-560; Karp, J. E. & Broder, S. Nat. Med. 1995, 1, 309-320; Hall, M. et al. Adv. Cancer Res. 1996, 68, 67108; Sher, C. J. Science, 1996, 274, 1672-1677). This observation has prompted an intensive search for small molecule CDK inhibitors. Inhibitors of Cdk enzymes may be expected to inhibit uncontrolled cell proliferation (D. W. Fry & M. D. Garrett, Curr. Opin. Endocrine, Metabolic Invet. Drugs, 2000, 2, 40-59.). Indeed, naturally occurring protein inhibitors of Cdks appear to perform this function providing strong validation for this approach. Introduction of p16 into lung cancer cell lines blocked entry into S phase and caused growth inhibition (Jin, X. et al. Cancer Res. 1995, 55, 3250-3253; Chintaia, S. K. et al. Oncogene 1997, 15, 2049-2057). Other studies have demonstrated a similar effect for p27 Craig, C. et al. Oneogene 1997, 14, 2283-2289). Growth inhibition also results from expression of antisense cyclin D1 or Dominant negative (DN) cdk2. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Acetyl-CoA carboxylase inhibitors Inventor(s): Harwood, H. James; (Ledyard, CT), Perry, David A.; (Mystic, CT) Correspondence: PFIZER INC.; PATENT DEPARTMENT, MS8260-1611; EASTERN POINT ROAD; GROTON; CT; 06340; US Patent Application Number: 20030187254 Date filed: February 20, 2003 Abstract: Acetyl Coenzyme A Carboxylase inhibitors, pharmaceutical compositions containing such compounds and the use of such compounds to treat for example, Metabolic Syndrome including atherosclerosis, diabetes and obesity. Excerpt(s): This invention relates to Acetyl-CoenzymeA Carboxylase (ACC) inhibitors, pharmaceutical compositions containing such inhibitors and the use of such inhibitors to treat, for example, metabolic syndrome, diabetes, obesity, atherosclerosis, and cardiovascular disease in mammals, including humans. Metabolic syndrome (a.k.a. insulin resistance syndrome, syndrome X) is a common clinical disorder that is defined as the presence of increased insulin concentrations in association with other disorders including visceral obesity, hyperlipidemia and dyslipidemia, hyperglycemia, hypertension, and sometimes hyperuricemia and renal dysfunction. Metabolic syndrome is considered by many as a common basic defect for type-2 diabetes, android obesity, dyslipidemia, and hypertension, leading to a clustering of these diseases. This syndrome has particular significance since it has been shown to be an antecedent of both type-2 diabetes and atherosclerosis, with cardiovascular events accounting for the majority of deaths in both populations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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AlphaAED and betaAED regulation of nuclear transcription, gene regulation, and/or gene expression Inventor(s): Loria, Roger M.; (Richmond, VA) Correspondence: HollisEden Pharmaceuticals, Inc.; Suite 400; 4435 Eastgate Mall; San Diego; CA; 92121; US Patent Application Number: 20030181434 Date filed: March 21, 2003 Abstract: The present invention provides a means to regulate nuclear transcription and/or gene expression. The present invention also provides a means to regulate the levels of PPAR-.gamma., COX-2 and/or NF.kappa.B in a patient. The method of the present invention involves administering.alpha.AED (or an analogue thereof) or.beta.AED (or an analogue thereof) or both to a patient in need of regulation of nuclear transcription and/or gene expression and/or levels of PPAR-.gamma., COX-2, and/or NF.kappa.B. The methods of the present invention can be used to control adipogenesis (i.e. to treat obesity), angiogenesis, atherosclerosis, mesenteric fat hypertrophy, inflammatory bowel disease, colitis, Alzheimer's disease, and inflammatory glial responses in the brain. The methods of the present invention can also be used for treating diabetes, for regulating the immune response, and for regulating inflammation in a patient. Excerpt(s): This application claims priority from U.S. Provisional Application No. 06/365,817, filed Mar. 21, 2002 (pending), which is hereby incorporated herein by reference in its entirety. The present invention relates to methods of regulating nuclear transcription and inflammation using.alpha.AED and.beta.AED. Peroxisome Proliferator Activated Receptors (PPARs) are a Subclass of nuclear hormone transcription factors that have tissue-specific distribution and regulate gene expression. Three major subtypes of PPARs have been described:.alpha.,.gamma., and.delta. The PPARs were originally thought to be exclusively linked to the control of lipid metabolism and homeostasis. However, studies have revealed that PPAR activation can influence a wide range of biologic activities including cellular proliferation, differentiation and apoptosis. This receptor family is implicated in a wide range of human conditions including, but not limited to, obesity, diabetes, atherosclerosis, inflammation, cancer, and aging (Isemann and Green, Nature 347:645-650 (1990); Collingwood et al, J. Mol. Endocrinol. 23:255-275 (1999); McKenna et al, Endocr. Rev. 20:321-344 (1999); Schoonjans et al, Curr. Opin. Lipidol. 8:159-166 (1997); and Greene et al, Prostaglandins & Other Lipid Mediators 62:45-73 (2000)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Antidiabetic agents Inventor(s): Gammill, Ronald B.; (East Lyme, CT) Correspondence: PFIZER INC.; PATENT DEPARTMENT, MS8260-1611; EASTERN POINT ROAD; GROTON; CT; 06340; US Patent Application Number: 20030199553 Date filed: February 19, 2003 Abstract: A compound of the formula 1wherein n, m, Z, R.sup.1, R.sup.5, R.sup.8, R.sup.9, R.sup.10 and R.sup.11 are as defined above, useful in the treatment of diabetes,
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insulin resistance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, cataracts, hyperglycemia, hypercholesterolemia, hypertension, hyperinsulinemia, hyperlipidemia, atherosclerosis, and tissue ischemia, particularly myocardial ischemia. Excerpt(s): The present invention relates to substituted 1H-(indole-2-carboxamides and 6H-thieno[2,3-b]pyrrole-5-carboxamides which are antidiabetic agents and as such are useful in the treatment of diabetes, insulin resistance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, cataracts, hyperglycemia, hypercholesterolemia, hypertension, hyperinsulinemia, hyperlipidemia, atherosclerosis, and tissue ischemia, particularly myocardial ischemia. This invention also relates to a method of using such compounds in the treatment of the above diseases in mammals, especially humans, and to the pharmaceutical compositions useful therefor. In spite of the early discovery of insulin and its subsequent widespread use in the treatment of diabetes, and the later discovery of and use of sulfonylureas, biguanides and thiazolidinediones, such as troglitazone, rosiglitazone or pioglitazone, as oral hypoglycemic agents, the treatment of diabetes remains less than satisfactory. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Antioxidant composition comprising propionyl L-carnitine and a flavonoid against throm-bosis and atherosclerosis Inventor(s): Cavazza, Claudio; (Roma, IT) Correspondence: NIXON & VANDERHYE, PC; 1100 N GLEBE ROAD; 8TH FLOOR; ARLINGTON; VA; 22201-4714; US Patent Application Number: 20030206895 Date filed: June 4, 2003 Abstract: A composition is disclosed which comprises as characterizing active ingredients propionyl L-carnitine and a flavonoid, typically quercetin or its 3-rutinoside, rutin, for the prevention and/or therapeutic treatment of various alterations and pathological states induced by free radicals and by thrombotic or atherosclerotic abnormalities, that may take the form of a dietary supplement, dietetic support or of an actual medicine. Excerpt(s): The present invention relates to a composition for the prevention and/or treatment of thrombotic or atherosclerotic abnormalities, allergic inflammatory reactions, diseases brought about by the release of free radicals and by increased platelet aggregation. Accordingly, the composition may take the form and exert the action of a dietary supplement or of an actual medicine, depending upon the support or preventive action, or the strictly therapeutic action, which the composition is intended to exert in relation to the particular individuals it is to be used in. (b) a flavonoid, preferably selected from the group comprising quercetin, rutin, myricetin, myricitrin or mixtures thereof or extracts of natural vegetable products containing such flavonoids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 203
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Antisense oligonucleotide directed toward mammalian vegf receptor genes and uses thereof Inventor(s): Sirois, Martin G.; (Quebec, CA) Correspondence: Marshall Gerstein & Borun; Sears Tower Suite 6300; 233 South Wacker Drive; Chicago; IL; 60606-6357; US Patent Application Number: 20030186920 Date filed: April 10, 2003 Abstract: The present invention provides antisense oligonucleotides that target the genes and mRNAs encoding mammalian VEGF receptors. Also provided are methods for designing and testing the antisense oligonucleotides. Such oligonucleotides can be used to reduce VEGF-induced inflammation and angiogenesis, for example, pathological angiogenesis, in mammals. Thus, the present invention also pertains to pharmaceutical compositions and formulations used in the treatment of mammals having a disease or disorder characterised by inflammation and/or pathological angiogenesis; including tumour growth and metastasis, ocular diseases (diabetic and perinatal hyperoxic retinopathies, age-related macular degeneration), arthritis, psoriasis and atherosclerosis. Excerpt(s): This application is a continuation in part of U.S. application Ser. No. 09/687,239, filed Oct. 13, 2000, which is hereby incorporated in its entirety. The present invention pertains to the field of antisense oligonucleotides for mammalian VEGF receptor genes and their use as anti-angiogenics and/or anti-inflammatory agents. Angiogenesis is a process by which new capillary vessels sprout from pre-existing ones, and can be summarised as the culmination of i) increased endothelial cell permeability to plasma proteins; ii) transmigration of inflammatory cells into extracellular matrix; iii) synthesis and release of degrading matrix molecules; iv) release of growth factors; v) migration and proliferation of endothelial cells to distant sites; and vi) capillary tube formation and vascular wall remodelling. Physiological angiogenesis is a highly coordinated process that exclusively occurs in healthy individuals under specific conditions, such as during wound healing, ovulation and pregnancy. At other times, the vasculature is extremely stable, with very low rates of new blood vessels (Fan et al., (1995) Trends Phaimacol. Sci. 16:57-66). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Apolipoprotein A-I mutant polynucleotides encoding same
proteins
having
cysteine
substitutions
and
Inventor(s): Forte, Trudy M.; (Berkeley, CA), Oda, Michael N.; (Benicia, CA) Correspondence: LAWRENCE BERKELEY NATIONAL LABORATORY; ONE CYCLOTRON ROAD, MAIL STOP 90B; UNIVERSITY OF CALIFORNIA; BERKELEY; CA; 94720; US Patent Application Number: 20030181372 Date filed: January 14, 2003 Abstract: Functional Apolipoprotein A-I mutant proteins, having one or more cysteine substitutions and polynucleotides encoding same, can be used to modulate paraoxonase's arylesterase activity. These ApoA-I mutant proteins can be used as therapeutic agents to combat cardiovascular disease, atherosclerosis, acute phase
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response and other inflammatory related diseases. The invention also includes modifications and optimizations of the ApoA-I nucleotide sequence for purposes of increasing protein expression and optimization. Excerpt(s): This applications claims priority to U.S. Ser. No. 60/348,683, filed Jan. 14, 2002, the contents which are hereby incorporated by reference in their entirety for all purposes. Applicants assert that the attached paper copy of the Sequence Listing for the utility application, "Apolipoprotein A-I Mutant Proteins Having Cysteine Substitutions and Polynucleotides Encoding Same," claiming priority to U.S. Provisional Patent Application No. 60/348,683, filed on Jan. 14, 2002, is identical to the Sequence Listing in computer readable form found on the accompanying computer disk, as required by 37 CFR 1.821(c) and is hereby incorporated by reference in its entirety. This invention generally relates to the field of HDL-associated proteins and paraoxonase activity. More specifically, the invention provides a method of modulating paraoxonase activity using apolipoprotein A-I mutant peptides having cysteine substitutions and polynucleotides encoding same. The invention has further application in the fields of treating and preventing cardiovascular diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Arylsulfonanilide ureas Inventor(s): Houze, Jonathan B.; (San Mateo, CA) Correspondence: TOWNSEND AND TOWNSEND AND CREW, LLP; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20030207864 Date filed: March 11, 2003 Abstract: The invention provides compounds, compositions and methods relating to novel arylsulfonanilide derivatives and their use as pharmacologically active agents. The compositions find particular use as pharmacological agents in the treatment of disease states, particularly cancer, psoriasis, vascular restenosis, infections, atherosclerosis and hypercholesterolemia, or as lead compounds for the development of such agents. Excerpt(s): This application claims priority from U.S. Ser. No. 60/100,888 filed Sept. 23, 1998, the disclosure of which is incorporated herein by reference. The present invention relates to arylsulfonanilide ureas and their use as pharmacologically active agents capable of lowering plasma cholesterol levels and inhibiting abnormal cell proliferation. A number of arylsulfonamides have recently been described for the treatment of disorders and conditions arising from abnormal cell proliferation and from elevated plasma cholesterol levels. See, for example, PCT publications WO 97/30677 and WO 98/05315. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Bicyclic pyrrolyl amides as glycogen phosphorylase inhibitors Inventor(s): Du Bois, Daisy Joe; (Palo Alto, CA) Correspondence: PFIZER INC.; PATENT DEPARTMENT, MS8260-1611; EASTERN POINT ROAD; GROTON; CT; 06340; US Patent Application Number: 20030195361 Date filed: February 14, 2003 Abstract: This invention relates to compounds of Formula I 1or stereoisomers, pharmaceutically acceptable salts or prod rugs thereof or a pharmaceutically acceptable salts of the prodrugs. This invention also relates to pharmaceutical compositions comprising a compound of Formula I, and to methods of treatment of diabetes, insulin resistance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, cataracts, hyperglycemia, hypercholesterolemia, hypertension, hyperinsulinemia, hyperlipidemia, atherosclerosis, or tissue ischemia. Excerpt(s): This invention relates to bicyclic pyrrolyl amides and pharmaceutical compositions comprising bicyclic pyrrolyl amides. This invention also relates to the treatment of diabetes, insulin resistance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, cataracts, hyperglycemia, hypercholesterolemia, hypertension, hyperinsulinemia, hyperlipidemia, atherosclerosis, and tissue ischemia, particularly myocardial ischemia, using the bicyclic pyrrolyl amides. In spite of the early discovery of insulin and its subsequent widespread use in the treatment of diabetes, and the later discovery of and use of sulfonylureas, biguanides and thiazolidenediones, such as troglitazone, rosiglitazone or pioglitazone, as oral hypoglycemic agents, the treatment of diabetes remains less than satisfactory. The use of insulin requires multiple daily doses, usually by self injection. Determination of the proper dosage of insulin requires frequent estimations of the sugar in urine or blood. The administration of an excess dose of insulin causes hypoglycemia, with effects ranging from mild abnormalities in blood glucose to coma, or even death. Treatment of non-insulin dependent diabetes mellitus (Type II diabetes, NIDDM) usually consists of a combination of diet, exercise, oral hypoglycemic agents, e.g., thiazolidenediones, and in more severe cases, insulin. However, the clinically available hypoglycemic agents can have side effects that limit their use, or an agent may not be effective with a particular patient. In the case of insulin dependent diabetes mellitus (Type I), insulin is usually the primary course of therapy. Hypoglycemic agents that have fewer side effects or succeed where others fail are needed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Combination of statins and sorbitol dehydrogenase inhibitors Inventor(s): Mylari, Banavara L.; (Waterford, CT) Correspondence: Gregg C. Benson; Pfizer Inc.; Patent Department, MS 4159; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030186994 Date filed: October 9, 2001 Abstract: This invention relates to pharmaceutical compositions comprising combinations of a statin, a prodrug thereof or a pharmaceutically acceptable salt of said statin or said prodrug and a sorbitol dehydrogenase inhibitor, a prodrug thereof or a
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pharmaceutically acceptable salt of said sorbitol dehydrogenase inhibitor or said prodrug, kits containing such combinations and methods of using such combinations to treat mammals, including humans, suffering from atherosclerosis and/or diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic microangiopathy, diabetic macroangiopathy, cataracts or foot ulcers. Excerpt(s): This invention relates to pharmaceutical combinations of a statin, a prodrug thereof or a pharmaceutically acceptable salt of said statin or said prodrug and a sorbitol dehydrogenase inhibitor, a prodrug thereof or a pharmaceutically acceptable salt of said sorbitol dehydrogenase inhibitor or said prodrug, kits containing such combinations and methods of using such combinations to treat mammals, including humans, suffering from atherosclerosis and/or diabetic complications such as, inter alia, diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic microangiopathy, diabetic macroangiopathy, cataracts or foot ulcers. This invention also relates to additive and synergistic combinations of a statin, a prodrug thereof or a pharmaceutically acceptable salt of said statin or said prodrug and a sorbitol dehydrogenase inhibitor, a prodrug thereof or a pharmaceutically acceptable salt of said sorbitol dehydrogenase inhibitor or said prodrug, whereby those additive and synergistic combinations are useful in treating mammals, including humans, suffering from atherosclerosis and/or diabetic complications such as, inter alia, diabetic neuropathy, diabetic nephropathy, diabetic cardiomyopathy, diabetic retinopathy, diabetic microangiopathy, diabetic macroangiopathy, cataracts or foot ulcers. The conversion of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate is an early and rate-limiting step in the cholesterol biosynthetic pathway. This step is catalyzed by the enzyme HMG-CoA reductase. Statins inhibit HMG-CoA reductase from catalyzing this conversion. As such, statins are collectively potent lipid lowering agents. Statins include such compounds as atorvastatin, disclosed in U.S. Pat. No. 4,681,893; atorvastatin calcium, disclosed in U.S. Pat. No. 5,273,995; simvastatin, disclosed in U.S. Pat. No. 4,444,784; pravastatin, disclosed in U.S. Pat. No. 4,346,227; cerivastatin, disclosed in U.S. Pat. No. 5,502,199; mevastatin, disclosed in U.S. Pat. No. 3,983,140; velostatin, disclosed in U.S. Pat. No. 4,448,784 and U.S. Pat. No. 4,450,171; fluvastatin, disclosed in U.S. Pat. No. 4,739,073; compactin, disclosed in U.S. Pat. No. 4,804,770; lovastatin, disclosed in U.S. Pat. No. 4,231,938; dalvastatin, disclosed in European Patent Application Publication No. 738510 A2; fluindostatin, disclosed in European Patent Application Publication No. 363934 A1; and dihydrocompactin, disclosed in U.S. Pat. No. 4,450,171. Each of the above is incorporated herein by reference. and is disclosed in U.S. Pat. No. 4,681,893, which is incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Combinations of ileal bile acid transport inhibitors and cholesteryl ester transfer protein inhibitors for cardiovascular indications Inventor(s): Connolly, Daniel T.; (Ballwin, MO), Glenn, Kevin C.; (Maryland Heights, MO), Keller, Bradley T.; (Chesterfield, MO), Schuh, Joseph R.; (St. Louis, MO), Sikorski, James A.; (Des Peres, MO), Smith, Mark E.; (Webster Groves, MO) Correspondence: BANNER & WITCOFF; 1001 G STREET N W; SUITE 1100; WASHINGTON; DC; 20001; US Patent Application Number: 20030203892 Date filed: July 23, 2002 Abstract: The present invention provides combinations of cardiovascular therapeutic compounds for the prophylaxis or treatment of cardiovascular disease including hypercholesterolemia, atherosclerosis, or hyperlipidemia. Combinations disclosed include an ileal bile acid transport inhibitor combined with a cholesteryl ester transfer protein (CETP) inhibitor. Excerpt(s): This application claims priority of U.S. provisional application Ser. No. 60/143,047 filed Jul. 7, 1999 and of U.S. provisional application Ser. No. 60/113,955 filed Dec. 23, 1998. The present invention relates to methods of treating cardiovascular diseases, and specifically relates to combinations of compounds, compositions, and methods for their use in medicine, particularly in the prophylaxis and treatment of hyperlipidemic conditions such as are associated with atherosclerosis, hypercholesterolemia, and other coronary artery disease in mammals. More particularly, the invention relates to ileal bile acid transporter (IBAT) inhibiting compounds. The invention also relates to cholesteryl ester transfer protein (CETP) activity inhibiting compounds. It is well-settled that hyperlipidemic conditions associated with elevated concentrations of total cholesterol and low-density lipoprotein (LDL) cholesterol are major risk factors for coronary heart disease and particularly atherosclerosis. Since high levels of LDL cholesterol increase the risk of atherosclerosis, methods for lowering plasma LDL cholesterol would be therapeutically beneficial for the treatment of atherosclerosis and other diseases associated with accumulation of lipid in the blood vessels. These diseases include, but are not limited to, coronary heart disease, peripheral vascular disease, and stroke. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions and methods for the diagnosis and treatment of disorders involving angiogenesis Inventor(s): Baker, Kevin P.; (Darnestown, MD), Ferrara, Napoleone; (San Francisco, CA), Gerber, Hanspeter; (San Francisco, CA), Gerritsen, Mary E.; (San Mateo, CA), Goddard, Audrey; (San Francisco, CA), Godowski, Paul J.; (Hillsborough, CA), Gurney, Austin L.; (Belmont, CA), Hillan, Kenneth J.; (San Francisco, CA), Marsters, Scot A.; (San Carlos, CA), Pan, James; (Etobicoke, CA), Stephan, Jean-Philippe F.; (Millbrae, CA), Watanabe, Colin K.; (Moraga, CA), Williams, P. Mickey; (Half Moon Bay, CA), Wood, William I.; (Hillsborough, CA), Ye, Weilan; (Foster City, CA) Correspondence: GENENTECH, INC.; 1 DNA WAY; SOUTH SAN FRANCISCO; CA; 94080; US Patent Application Number: 20030186866 Date filed: August 16, 2002
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Abstract: Compositions and methods are disclosed for stimulating or inhibiting angiogenesis and/or cardiovascularization in mammals, including humans. Pharmaceutical compositions are based on polypeptides or antagonists thereto that have been identified for one or more of these uses. Disorders that can be diagnosed, prevented, or treated by the compositions herein include trauma such as wounds, various cancers, and disorders of the vessels including atherosclerosis and cardiac hypertrophy.In addition, the present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Excerpt(s): The present invention relates to compositions and methods useful for the modulation (e.g., promotion or inhibition) of angiogenesis and/or cardiovascularization in mammals in need of such biological effect. The present invention further relates to the diagnosis and treatment of disorders involving angiogenesis (e.g., cardiovascular as well as oncological disorders). Angiogenesis, defined as the growth or sprouting of new blood vessels from existing vessels, is a complex process that primarily occurs during embryonic development. Under normal physiological conditions in adults, angiogenesis takes place only in very restricted situations such as hair growth and wounding healing (Auerbach, W. and Auerbach, R., 1994, Pharmacol Ther 63(3):265-311; Ribatti et al., 1991, Haematologica 76(4):311-20; Risau, 1997, Nature 386(6626):671-4). Unregulated angiogenesis has gradually been recognized to be responsible for a wide range of disorders, including, but not limited to cardiovascular disease, cancer, rheumatoid arthritis, psoriasis and diabetic retinopathy (Folkman, 1995, Nat Med 1(1):27-31; Isner, 1999, Circulation 99(13): 1653-5; Koch, 1998, Arthritis Rheum 41(6):951-62; Walsh, 1999, Rheumatology (Oxford) 38(2): 103-12; Ware and Simons, 1997, Nat Med 3(2): 158-64). Heart failure affects approximately five million Americans, and new cases of heart failure number about 400,000 each year. It is the single most frequent cause of hospitalization for people age 65 and older in the United States. Recent advances in the management of acute cardiac diseases, including acute myocardial infarction, are resulting in an expanding patient population that will eventually develop chronic heart failure. From 1979 to 1995, hospitalizations for congestive heart failure (CHF) rose from 377,000 to 872,000 (a 130 percent increase) and CHF deaths increased 116 percent. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for the treatment and diagnosis of cardiovascular disease Inventor(s): Falb, Dean A.; (Wellesley, MA), Gimbrone, Michael A. JR.; (Jamaica Plain, MA) Correspondence: PENNIE & EDMONDS LLP; 1667 K Street, N.W.; Washington; DC; 20006; US Patent Application Number: 20030188327 Date filed: July 2, 2002 Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Specifically, the present invention identifies and describes genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-
Patents 209
cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in cardiovascular disease. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease. Moreover, the present invention provides methods for the diagnostic monitoring of patients undergoing clinical evaluation for the treatment of cardiovascular disease, and for monitoring the efficacy of compounds in clinical trials. Additionally, the present invention describes methods for the diagnostic evaluation and prognosis of various cardiovascular diseases, and for the identification of subjects exhibiting a predisposition to such conditions. Excerpt(s): This application is a continuation-in-part of co-pending application Ser. No. 08/485,573, filed Jun. 7, 1995, which is a continuation-in-part of co-pending application Ser. No. 08/386,844, filed Feb. 10, 1995, each of which is hereby incorporated by reference in its entirety. The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states are identified. Genes are also identified via the ability of their gene products to interact with other gene products involved in cardiovascular disease. The genes identified may be used diagnostically or as targets for therapeutic intervention. In this regard, the present invention provides methods for the identification and therapeutic use of compounds in the treatment and diagnosis of cardiovascular disease. Additionally, methods are provided for the diagnostic monitoring of patients undergoing clinical evaluation for the treatment of cardiovascular disease, for monitoring the efficacy of compounds in clinical trials, and for identifying subjects who may be predisposed to cardiovascular disease. Cardiovascular disease is a major health risk throughout the industrialized world. Atherosclerosis, the most prevalent of cardiovascular diseases, is the principal cause of heart attack, stroke, and gangrene of the extremities, and thereby the principle cause of death in the United States. Atherosclerosis is a complex disease involving many cell types and molecular factors (for a detailed review, see Ross, 1993, Nature 362: 801-809). The process, in normal circumstances a protective response to insults to the endothelium and smooth muscle cells (SMCs) of the wall of the artery, consists of the formation of fibrofatty and fibrous lesions or plaques, preceded and accompanied by inflammation. The advanced lesions of atherosclerosis may occlude the artery concerned, and result from an excessive inflammatory-fibroproliferative response to numerous different forms of insult. For example, shear stresses are thought to be responsible for the frequent occurrence of atherosclerotic plaques in regions of the circulatory system where turbulent blood flow occurs, such as branch points and irregular structures. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for treating cardiovascular disorders Inventor(s): Stocker, Roland; (New South Wales, AU) Correspondence: FISH & RICHARDSON PC; 225 FRANKLIN ST; BOSTON; MA; 02110; US Patent Application Number: 20030176511 Date filed: February 28, 2003
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Abstract: The present invention relates compositions and methods for the prophylactic or therapeutic treatment of cardiovascular diseases, particularly restenosis and atherosclerosis. These compositions comprise an effective promotor of reendothelialization, preferably probucol or an analogue thereof, and an inhibitor of lipoprotein oxidation, preferably a probucol-derived bisphenol. Alternatively, the said compositions may comprise a compound that possesses both re-endothelializationpromoting and lipoprotein oxidation-inhibitory effects. This invention further relates to compositions and methods for promoting re-endothelialization. Excerpt(s): The present invention relates to a method of prophylactic or therapeutic treatment of cardiovascular diseases, particularly restenosis and atherosclerosis by a process which both induces re-endothelialization and inhibits the oxidation of lipoproteins. The invention further provides a method of promoting reendothelialization preferably in a vessel wall. Heart disease can result from many factors relating to poor functioning of heart tissue which may manifest in commonly known conditions such as angina, stroke or heart attack. The underlying mechanisms of heart disease are not completely understood. However, it is known that lipid such as cholesterol are actively involved. These can all contribute to atherosclerosis, i.e., the clogging of arteries, and gradually building deposits that eventually cause heart disease. Atherosclerosis causes heart attacks, strokes and leads to the death of almost 50% of Australians. The disease involves intimal thickening and the deposition of lipid (primarily derived from low-density lipoprotein, LDL) in the sub-endothelial space. As lesions develop, the elastic lamina separates the intima from the media, allowing proliferating smooth muscle cells to infiltrate the intima and to deposit increased amounts of extra-cellular matrix. A necrotic core (composed of dead cells, lipid deposits and cholesterol crystals) may develop and the disease can also involve the medial layer. Atherosclerosis can develop silently for many years without symptoms. Often serious events are precipitated when a blood clot lodges in the vessel at a site that is already partially blocked as a result of atherosclerosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions for improving lipid metabolism Inventor(s): Doi, Hideyuki; (Miyagi, JP), Komatsu, Hiromichi; (Miyagi, JP), Satomi, Susumu; (Miyagi, JP) Correspondence: BROWDY AND NEIMARK, P.L.L.C.; 624 NINTH STREET, NW; SUITE 300; WASHINGTON; DC; 20001-5303; US Patent Application Number: 20030183091 Date filed: April 14, 2003 Abstract: This invention aims at providing compositions and foods for improving lipid metabolism which improve the metabolism of lipids and thus are expected to contribute to the prevention and amelioration of hyperlipemia, obesity, atherosclerosis and the like. The invention provides compositions for improving lipid metabolism, compositions for preventing or treating hyperlipemia, compositions for preventing or treating obesity and foods for preventing or ameliorating hyperlipemia and obesity, which contain valine as an active ingredient. Excerpt(s): This invention relates to compositions for improving lipid metabolism which improve the metabolism of lipids and thus can be expected to contribute to the prevention and amelioration of obesity, hyperlipemia, atherosclerosis and the like. It
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further relates to compositions for preventing or treating hyperlipemia and foods for preventing or ameliorating hyperlipemia. It still further relates to compositions for preventing or treating obesity and foods for preventing or ameliorating obesity. In recent years, lipid intake has been increasing in Japan with the tendency toward improved and Western-style eating habits, which brings about a problem of excessive fat intake. The excessive fat intake causes obesity and an increase in the serum lipid level and consequently heightens the risk of the onset of various complications thereof (for example, circulatory diseases, in particular, coronary and cerebral vascular accidents and life-style related diseases such as certain cancers including breast cancer and colon cancer). Thus, it becomes a serious social problem from the viewpoint of maintaining and improving national health. It has been pointed out that an increase in the levels of cholesterol in the blood is one of the risk factors of the onset of circulatory diseases. Recently, high concentrations of triacylglycerol (triglyceride) in the blood have also attracted attention as another risk factor independent from those of cholesterol. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Direct arterial infiltration for production of vascular pathology Inventor(s): Edelman, Elazer; (Brookline, MA), Rogers, Campbell; (Westwood, MA), Welt, Frederick G.; (Newton, MA) Correspondence: Attn: Matthew E. Connors; Samuels, Gauthier & Stevens, LLP; Suite 3300; 225 Franklin Street; Boston; MA; 02110; US Patent Application Number: 20030192555 Date filed: May 5, 2003 Abstract: A method of producing a vascular lesion in an animal that resembles atherosclerosic lesions in humans. The method includes introducing cholesterol enriched with LDL or cholesterol enriched with LDL and monocytes, macrophages, leukocytes, smooth muscle cells or platelets into a proliferative lesion created by standard methods, to promote atherosclerosis. Excerpt(s): The invention relates to the field of the local infiltration of cells, cell products or chemical and pharmacological compounds from the lumen of a tubular structure into or around the wall of that structure. In particular this invention is for the infusion of cells, cell products or chemical and pharmacological compounds, alone or in some form of a polymeric material, from an endovascular catheter into or around the wall of a blood vessel. The infusion can be utilized to produce an animal model of atherosclerosis, and in particular to create a vascular lesion in an animal model that more closely resembles the lesions of atherosclerosis seen in humans as well as to the possibility of introducing cellular constituents, cell products or pharmacological agents in order to ameliorate the atherosclerotic or restenotic process. The infusion can also be used to treat the blood vessel wall through the infusion of cells that elaborate therapeutic compounds. Animal models have been invaluable in understanding the basic processes of vascular biology in atherosclerotic and restenotic lesions. However, countless examples of therapies that are advantageous in animal models prove unsuccessful in humans. This has led to skepticism as to the degree to which current experimental models predict human responses. The differences are usually attributed to the inter-species differences in biologic responses. Atherogenesis is the formation of lipid deposits in the intima of arteries that can cause the arterial surface to bulge out into the arterial lumen. In humans, atherogenesis is the result of many different factors acting over a prolonged period of time. Initial lesions called fatty streaks may develop
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early in life and are manifest by the presence of lipids and macrophages in the innermost layer of the vessel wall. There are many atherogenic determinants including prolonged exposure to factors such as hyperlipidemia, diabetes, cigarette smoking, and hypertension, which lead to further inflammation, endothelial activation, smooth muscle cell proliferation, matrix synthesis, monocyte recruitment, and eventually necrosis, lipid accumulation, and often, calcification. The mature atherosclerotic plaque contains two main components; the first is a soft, lipid-rich core with necrotic debris. The second is a fibrous cap separating the core from the lumen and consisting of smooth muscle cells and collagen. It remains unclear whether this lipid core develops by direct infiltration and deposition of extracellular lipid with subsequent recruitment of macrophages, or whether macrophages endocytose lipid and subsequently necrose leaving lipid and necrotic debris behind. The oxidative state of the lipid core is crucial in determining it's toxic potential. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Early detection marker for chronic inflammatory associated diseases Inventor(s): Pereira, Heloise Anne; (Edmond, OK) Correspondence: DUNLAP, CODDING & ROGERS P.C.; PO BOX 16370; OKLAHOMA CITY; OK; 73114; US Patent Application Number: 20030170745 Date filed: March 7, 2003 Abstract: The present invention in one embodiment is an early detection marker for chronic inflammatory-associated diseases, including atherosclerosis, Alzheimer's disease, asthma, rheumatoid arthritis, osteoarthritis, and inflammatory diseases of the bowel such as Crohn's disease, Ulcerative colitis, Irritable bowel syndrome and Inflammatory bowel disease. The method, for example may comprise (1) obtaining a fluid sample from the subject, wherein the subject does not have an acute bacterial or viral infection when the fluid sample is obtained, (2) testing the fluid sample for a circulating or secreted CAP37 protein, and (3) concluding that the subject has a chronic inflammatory-associated disease when the CAP37 protein is detected in the fluid sample. The fluid sample may comprise serum, plasma, or cerebrospinal fluid, for example, or any other body fluid exposed to endothelial, vascular, or neuronal secretions. Excerpt(s): This application claims the benefit of U.S. Serial No. 60/363,114, filed Mar. 8, 2002, which is hereby expressly incorporated herein by reference in its entirety. The present invention relates to, but is not limited to, methods for detecting inflammatoryassociated diseases by detecting CAP37 proteins in a body fluid. Cationic Antimicrobial Protein of M.sub.r 37 kDa (CAP37) was originally isolated from granule extracts of human polymorphonuclear leukocytes (PMN) in 1984 (1). The amino acid sequence of PMN-CAP37 revealed its relation to members of the serine protease family that have a conserved catalytic active site consisting of his-57, asp-102 and ser-195 in the charge relay system (2). Of these sites, the conserved histidine and serine of the catalytic triad have been replaced with serine and glycine residues, respectively, rendering CAP37 ineffective as a serine protease (2,3). However, CAP37 has been demonstrated to have a diverse and exciting repertoire of functions. It was first analyzed regarding its bactericidal properties against Gram negative bacteria including, but not limited to, Salmonella typhimurium, Escherichia coli and Pseudomonas aeruginosa (4) and its ability to bind to and neutralize lipopolysaccharide (LPS)(5). Subsequently we showed
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CAP37 to be a potent chemoattractant for monocytes (6). Additionally, regarding its effects on the monocyte, CAP37 has been reported to stimulate their survival and thrombospondin secretion (7), also to enhance the LPS-stimulated release of prostaglandin E2 (8), interleukin 6 (IL-6)(9) and tumor necrosis factor-alpha (TNF.alpha.)(8-10). To add even further to its extensive range of known functions, CAP37 has been demonstrated to stimulate the reversible contraction of fibroblasts and endothelial cells (7) and to activate endothelial cell protein kinase C (PKC)(11). Recently, CAP37 released from stimulated PMN was reported to be taken up and sequestered in nearby endothelial mitochondria and has been suggested to protect against apoptosis (12). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Fomulation Inventor(s): Wikstrand, John; (Gothenburg, SE), Berglund, Goran; (Malmo, SE) Correspondence: David P Halstead; Ropes & Gray; One International Place; Boston; MA; 02110-2624; US Patent Application Number: 20030191177 Date filed: December 13, 2002 Abstract: The present invention relates to pharmaceutical formulations comprising a betablocker, in a maintenance dose lower than 50 mg, particularly in the range of 25 to 47 mg, optionally containing a cholesterol lowering agent, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier, as well as a method of treatment and use of the formulations for the treatment of atherosclerosis and related diseases. Excerpt(s): The present invention relates to pharmaceutical formulations comprising a betablocker, in a maintenance dose lower than 50 mg, in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier, as well as a method of treatment and use of the formulations for the treatment of atherosclerosis and related conditions. There is a constant need for new medications to further reduce the risk of atherosclerotic disease, since this is one of the industrial world's most common health problems. The administration of combinations of.beta.sub.1 selective blockers and lipidlowering drugs to healthy volunteers in order to observe the effects on fat metabolism, ammonia levels and the perception of effort during exercise, was disclosed in Br. J. Clin Pharmacol 1997 vol 43, no 3 pages 291-300. The combinations studied were 1) metoprolol (controlled release) and fluvastatin 2) metoprolol (controlled release) and bezafibrate 3) atenolol (normal release) and fluvastatin and 4) atenolol (normal release) and bezafibrate. The paper concluded that that these four combinations each caused significant reductions in fat metabolism increased plasma ammonia concentrations and raised the perception of exercise. Combination 1) had the least adverse effect but the formulation difference was thought to be a significant factor in explaining the differences observed with respect to combination 3). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Gene therapy approaches to supply apolipoprotein A-I agonists and their use to treat dyslipidemic disorders Inventor(s): Buttner, Klaus; (Epfenbach, DE), Cornut, Isabelle; (Edingen-Neckarhausen, DE), Dasseux, Jean-Louis; (Mannheim, DE), Dufourcq, Jean; (Pessac, FR), Metz, Gunther; (Edingen-Neckarhausen, DE), Sekul, Renate; (Ladenburg, DE) Correspondence: PENNIE AND EDMONDS; 1155 AVENUE OF THE AMERICAS; NEW YORK; NY; 100362711 Patent Application Number: 20030208059 Date filed: October 29, 2002 Abstract: The invention relates to genetic approaches to supply nucleotide sequences encoding modified forms of the native forms of apolipoprotein A-I (ApoA-I): mature ApoA-I, preproApoA-I and proApoA-I; including native ApoA-I modified to contain ApoA-I agonists, peptides which mimic the activity of ApoA-I; ApoA-I superagonists, peptides which exceed the activity of native ApoA-I; and modified native ApoA-I having one or more amphipathic helices replaced by the nucleotide sequences of one or more ApoA-I agonists; for the treatment of disorders associated with dyslipoproteinemia, including cardiovascular disease, atherosclerosis, restenosis, hyperlipidemia, and other disorders such as septic shock. Excerpt(s): The invention relates to gene therapy approaches to supply nucleotide sequences encoding modified forms of the native forms of apolipoprotein A-I (ApoA-I) i.e., mature ApoA-I, preproApoA-I and proApoA-I; ApoA-I peptides; ApoA-I agonists and superagonists, peptides which mimic or exceed the activity of native ApoA-I; and the native ApoA-I gene for the treatment of disorders associated with dyslipoproteinemia, including cardiovascular disease, atherosclerosis, restenosis, hyperlipidemia, and other disorders such as septic shock. Circulating cholesterol is carried by plasma lipoproteins--particles of complex lipid and protein composition that transport lipids in the blood. Low density lipoproteins (LDL), and high density lipoproteins (HDL) are the major cholesterol carriers. LDL are believed to be responsible for the delivery of cholesterol from the liver (where it is synthesized or obtained from dietary sources) to extrahepatic tissues in the body. The term "reverse cholesterol transport" describes the transport of cholesterol from extrahepatic tissues to the liver where it is catabolized and eliminated. It is believed that plasma HDL particles play a major role in the reverse transport process, acting as scavengers of tissue cholesterol. The evidence linking elevated serum cholesterol to coronary heart disease is overwhelming. For example, atherosclerosis is a slowly progressive disease characterized by the accumulation of cholesterol within the arterial wall. Compelling evidence supports the concept that lipids deposited in atherosclerotic lesions are derived primarily from plasma LDL; thus, LDLs have popularly become known as the "bad" cholesterol. In contrast, HDL serum levels correlate inversely with coronary heart disease--indeed, high serum levels of HDL are regarded as a negative risk factor. It is hypothesized that high levels of plasma HDL are not only protective against coronary artery disease, but may actually induce regression of atherosclerotic plaques (e.g., see Badimon et al., 1992, Circulation 86 (Suppl. III):86-94). Thus, HDL have popularly become known as the "good" cholesterol. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Genes expressed in treated foam cells Inventor(s): Kaser, Matthew R.; (Castro Valley, CA), Mikita, Thomas; (San Francisco, CA), Porter, J. Gordon; (Newark, CA), Shiffman, Dov; (Palo Alto, CA) Correspondence: INCYTE GENOMICS, INC.; 3160 PORTER DRIVE; PALO ALTO; CA; 94304; US Patent Application Number: 20030194721 Date filed: September 18, 2002 Abstract: The invention relates to isolated polynucleotides, purified polypeptides, and compositions comprising pluralities of polynucleotides that are differentially expressed when foam cells are treated with oxidized low-density lipoprotein and LPS as associated with atherosclerosis. The invention also presents the use of the polynucleotides as elements on a substrate and provides methods for using the polynucleotides and polypeptides. Excerpt(s): This application claims benefit of provisional application Serial No. 60/323,784, filed Sep. 19, 2001. The present invention relates to a combination of polynucleotides which may be used to detect the differential expression of genes in human foam cells treated with oxidized low-density lipoprotein and/or lipopolysaccharide (LPS). In particular, the combination may be used in the diagnosis of conditions, diseases, and disorders associated with cardiovascular disease. Atherosclerosis and the associated coronary artery disease and cerebral stroke represent the most common cause of death in industrialized nations. Although certain key risk factors have been identified, a full molecular characterization that elucidates the causes and provides care for these associated diseases has not been achieved. Molecular characterization of growth and regression of atherosclerotic vascular lesions requires identification of the genes that contribute to formation of the lesion including growth, stability, dissolution, rupture and, most lethally, induction of occlusive vessel thrombus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Human chemokine Inventor(s): Holloway, James L.; (Seattle, WA) Correspondence: Phillip B.C. Jones, J.D., Ph.D.; ZymoGenetics, Inc.; 1201 Eastlake Avenue East; Seattle; WA; 98102; US Patent Application Number: 20030170824 Date filed: May 14, 2002 Abstract: Chemokines are implicated in inflammation, ischemia and reperfusion injury, wound healing, allergies, as well as bacterial and viral pathogenesis. Moreover, chemokines may be involved in chronic diseases such as arthritis, asthma, and atherosclerosis. The present invention provides a new form of chemokine, designated as "Zchemo14." Excerpt(s): This application claims the benefit of U.S. Provisional application No. 60/291,778 (filed May 17, 2001), the contents of which are incorporated by reference. The present invention relates generally to a gene that encodes a new human protein. In particular, the present invention relates to a novel protein, designated "Zchemo14," and to nucleic acid molecules encoding Zchemo14. Chemotactic cytokines were originally identified in supernatants of stimulated leukocyte cell cultures, and were initially
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characterized through their chemotactic effects on a variety of leukocytes. Subsequent isolation of several chemotactic cytokines has led to the discovery of a family of structurally and functionally homologous molecules now known as "chemokines" (see, for example, Schnell, The Cytokine Handbook, (Academic Press 1994)). In vivo, chemokines have pro-inflammatory, pyrogenic, chemokinetic, myelosuppressive or hematopoietic effects; primarily, chemokines regulate inflammatory and immunoregulatory processes through their selective recruitment and activation of leukocytes. Chemokines are 8 to 16 kDa soluble basic proteins that are produced and released by a variety of cell types during an acute inflammatory response to injury, allergens, or microbial and viral infections. Moreover, chemokine involvement is apparent in some chronic inflammatory states such as arthritis, asthma, and eczema. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Identification of genes involved in restenosis and in atherosclerosis Inventor(s): Durrani, Sarfraz; (Arlington, VA), Epstein, Stephen E.; (Rockville, MD) Correspondence: Heller Ehrman White & McAuliffe LLP; Intellectual Property Department; Suite 300; 1666 K Street, N.W.; Washington; DC; 20006; US Patent Application Number: 20030170673 Date filed: October 2, 2002 Abstract: Methods are provided for estimating the risk of developing restenosis or of atherosclerosis in an individual. Methods and compositions for treating or preventing restenosis or atherosclerosis also are provided. Excerpt(s): Coronary artery disease is a disease that is endemic in Western society. In this disease the arteries that supply blood to the heart muscle become narrowed by deposits of fatty, fibrotic, or calcified material on the inside of the artery. The build up of these deposits is called atherosclerosis. Atherosclerosis reduces the blood flow to the heart, which starves the heart muscle of oxygen, leading to either/or angina pectoris (chest pain), myocardial infarction (heart attack), and congestive heart failure. One common treatment to clear arteries blocked by atherosclerosis is balloon angioplasty, more formally referred to as percutaneous transluminal coronary angioplasty (PTCA). This treatment involves opening up a blocked artery by inserting and inflating a small balloon, which compresses and rearranges the blocking plaque against the arterial wall. After deflation and removal of the balloon, the arterial lumen is enlarged, thereby improving blood flow. About one million angioplasty procedures are performed each year. In a significant number of angioplasty patients the treated artery narrows again within six months of the procedure in a process called restenosis. Restenosis begins soon after angioplasty, wherein the increased size of the vascular lumen (the open channel inside the artery) becomes gradually occluded by the proliferation of smooth muscle cells. Approximately 20 to 30% of all angioplasty patients experience restenosis to the extent that they must undergo repeated angioplasty or even coronary bypass surgery. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Inhibiting development of microvessels withins coronary or peripheral vessel walls for restenosis/atherosclerosis prevention or therapy Inventor(s): Epstein, Stephen E.; (Rockville, MD), Fuchs, Shmuel; (Rockville, MD), Kornowski, Ran; (Rockville, MD), Leon, Martin; (Bethesda, MD) Correspondence: FROMMER LAWRENCE & HAUG; 745 FIFTH AVENUE- 10TH FL.; NEW YORK; NY; 10151; US Patent Application Number: 20030191055 Date filed: January 5, 2000 Abstract: Disclosed and claimed are compositions and methods for therapy and/or prevention of restenosis and/or atherosclerosis. The compositions can include an agent for inhibiting VEGF and an agent for inducing vessel maturation; for instance, the soluble VEGF receptor and ang-1. Embodiments can include kits. Excerpt(s): This application claims priority from U.S. application Ser. No. 60/115,977, filed Jan. 15, 1999; and, that application and all documents cited therein, and all documents cited or referenced in documents cited in that application, are hereby incorporated herein by reference. The present invention relates to compositions and methods for the preventing and/or treatment of restenosis and/or atherosclerosis. The present invention further relates to compositions and methods for inhibiting the development of microvessels within the wall of coronary and/or peripheral vessels. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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LIGNAN COMPLEX DERIVED FROM FLAXSEED HYPERCHOLESTEROLEMIC AND ANTI-ATHEROSCLEROTIC AGENT
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Inventor(s): Prasad, Kailash; (Saskatoon, CA) Correspondence: KIRBY EADES GALE BAKER; Station D; P.O. Box 3432; Ottawa; ON; K1P 6N9; CA Patent Application Number: 20030212007 Date filed: May 10, 2002 Abstract: A method is described for treating hypercholesterolemic atherosclerosis or for reducing total cholesterol while raising high-density lipoportoein cholesterol. It involves administering to a patient a substantially pure complex derived from flaxseed and containing secoisolariciresinol diglucoside (SDG), cinnamic acid glucosides and hydroxymethyl glutaric acid. Excerpt(s): This invention relates to a method for the use of a lignan complex isolated from flaxseed for the treatment of atherosclerosis, e.g. reducing or preventing the development of hypercholesterolemic atherosclerosis, for reducing total cholesterol and for raising HDL-C in blood. Hypercholesterolemia is a major risk factor for atherosclerosis (narrowing of the artery due to deposition of fat in the arterial wall) and related occlusive vascular diseases such as heart attack, stroke and other peripheral vascular diseases. Heart disease is the number one killer. Hypercholesterolemic atherosclerosis has been reported to be associated with oxidative stress increase in levels of reactive oxygen species (ROS), production of ROS by polymorphonuclear leukocytes as assessed by chemiluminescence (PMNL-CL), and a decrease in the antioxidant reserve. Pretreatment with antioxidants (vitamin E, probucol, garlic, purpurogallin, secoisolariciresinol diglucoside) reverses the effects of
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hypercholesterolemia. Flaxseed which is a rich source of.alpha.-linolenic acid and richest source of plant lignans has been shown to be effective in reducing hypercholesterolemic atherosclerosis without lowering serum levels of cholesterol. Using flaxseed which has very low.alpha.-linolenic acid, has shown that antiatherogenic activity of flaxseed is not due to.alpha.-linolenic acid but may be due to lignan component of flaxmeal. Presently the treatment of hypercholesterolemia and hypercholesterolemic atherosclerosis is to reduce hypercholesterolemia by using various lipid lowering agents such as bile acid sequestrant (cholestyramine, colestipol), nicotinic acid, HMG-CoA reductase inhibitor (lovastatin, provastatin, simvastatin, fluvastatin and atrovastatin) and gemfibrozil. Recently probucol which has both antioxidant and lipid lowering activity and vitamin E which has antioxidant activity have been used to prevent atherosclerosis and restenosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for treating hypercholesterolemia, hyperlipidemia, and atherosclerosis Inventor(s): Cherukuri, Reddy Sastry V.; (Folsom, CA), Cheruvanky, Rukmini; (Folsom, CA), Lynch, Ike; (El Dorado Hills, CA), McPeak, Patricia; (El Dorado Hills, CA), Qureshi, Asaf A.; (Madison, WI) Correspondence: TOWNSEND AND TOWNSEND AND CREW, LLP; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20030203058 Date filed: May 5, 2003 Abstract: A method for reducing mammalian serum total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels, by ingesting a stabilized rice bran derivative selected from the group consisting of an enzyme treated stabilized rice bran, an insolubilized fraction and mixtures thereof, thereby reducing serum total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels in said mammal. Excerpt(s): The present application is related to U.S. Patent Application No. 60/057,870, filed Sep. 2, 1997, the teachings of which are incorporated herein by reference. The present invention relates to methods for treating hypercholesterolemia, hyperlipidemia, and atherosclerosis in mammals by ingesting a stabilized rice bran derivative. Hypercholesterolemia is a condition with elevated levels of circulating total cholesterol, LDL-cholesterol and VLDL-cholesterol as per the guidelines of the Expert Panel Report of the National Cholesterol Educational Program (NCEP) of Detection, Evaluation of Treatment of high cholesterol in adults (see, Arch. Int. Med. (1988) 148, 36-39). In particular, high level of LDL and VLDL are positively associated with coronary arteriosclerosis while the high levels of high density lipoproteins (HDL) are negative risk factors. The role of LDL oxidation is gaining much attention in the literature. It is well documented that LDL becomes oxidatively stressed under pathological conditions and is no longer recognized by the LDL receptors. The oxidized LDL is taken up by macrophages within the subendothelial space, leading to the formation of fatty streaks which are the basis of most advanced lesions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of treating anemia Inventor(s): Creasy, Caretha; (Erdenheim, PA), Dillon, Susan B.; (Chester Springs, PA), Lord, Kenneth A.; (Collegeville, PA) Correspondence: Ratner & Prestia; P.O. Box 980; Valley Forge; PA; 19482-0980; US Patent Application Number: 20030176375 Date filed: May 14, 2001 Abstract: hYAK3-2 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing hYAK3-2 polypeptides and polynucleotides in the design of protocols for the treatment of bone loss including osteoporosis; inflammatory diseases such as Adult Respiratory Disease Syndrome (ARDS), Rheumatoid arthritis, Osteoarthritis, Inflammatory Bowel Disease (IBD), psoriasis, dermatitis, asthma, allergies; infections such as bacterial, fungal, protozoan and viral infections, particularly infections caused by HIV-1 or HIV-2; HIV-associated cachexia and other immunodeficiency disorders; septic shock; pain; injury; cancers including testicular cancer; anorexia; bulimia; neutropenia; cytopenia; anemias, including anemias due to renal insufficiency or to chronic disease, such as autoimmunity or cancer, and drug-induced anemias; polycythemia; myelosuppression; Parkinson's disease; cardiovascular disease including restenosis, atherosclerosis, acute heart failure, myocardial infarction; hypotension; hypertension; urinary retention; angina pectoris; ulcers; benign prostatic hypertrophy; and psychotic and neurological disorders, including anxiety, schizophrenia, manic depression, delirium, dementia, severe mental retardation and dyskinesias, such as Huntington's disease or Gilles dela Tourett's syndrome., among others, and diagnostic assays for such conditions. Excerpt(s): This application claims priority to U.S. Ser. No. 60/118,045 filed Feb. 1, 1999, which is incorporated by reference in its entirety. This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to a serine/threonine protein kinase, hereinafter referred to as hYAK3-2. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. A number of polypeptide growth factors and hormones mediate their cellular effects through a signal transduction pathway. Transduction of signals from the cell surface receptors for these ligands to intracellular effectors frequently involves phosphorylation or dephosphorylation of specific protein substrates by regulatory protein serine/threonine kinases (PSTK) and phosphatases. Serine/threonine phosphorylation is a major mediator of signal transduction in multicellular organisms. Receptor-bound, membranebound and intracellular PSTKs regulate cell proliferation, cell differentiation and signalling processes in many cell types. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and compositions relating to fortilin, an anti-apoptotic molecule, and modulators of fortilin Inventor(s): Fujise, Ken; (Houston, TX), Yeh, Edward T.H.; (Houston, TX) Correspondence: FULBRIGHT & JAWORSKI L.L.P.; A REGISTERED LIMITED LIABILITY PARTNERSHIP; SUITE 2400; 600 CONGRESS AVENUE; AUSTIN; TX; 78701; US Patent Application Number: 20030172388 Date filed: October 30, 2001 Abstract: The polypeptide Fortilin (also known as Translationally Controlled Tumour Protein, TCTP) specifically interacts with p53, a tumor suppressor involved in the induction of apoptosis and the normal growth regulation of a cell. Fortilin also specifically binds MCL1 (Myeloid Cell Leukemia 1). Fortilin has the ability to prevent apoptosis, which may be unregulated in hyperproliferative cells. The present invention is directed at compositions and methods involving a Fortilin modulator, which can induce apoptosis, for the prevention, treatment, or diagnosis of hyperproliferative diseases and conditions, including cancer and atherosclerosis. It is directed also at compositions and methods involving Fortilin, which can inhibit apoptosis, for the treatment of diseases and condition characterized by apoptosis, including certain vascular conditions. Excerpt(s): The present application claims priority to co-pending U.S. Provisional Patent Application Serial No. 60/244,416 filed on Oct. 30, 2000. The entire text of the abovereferenced disclosure is specifically incorporated herein by reference without disclaimer. The government may own rights in the present invention pursuant to grant number 1KO8HL04015 from the National Institutes of Health. The present invention relates generally to the fields of biochemistry, molecular biology, and diagnosis and therapy for hyperproliferative cell diseases and conditions, such as cancer and atherosclerosis. More particularly, it concerns a Fortilin polypeptide, the gene or transcript encoding it, modulators of Fortilin and their relevance to cancer and vascular diseases. Heart disease and cancer are the leading causes of death, respectively, in the United States. In 1997, 41.2 percent of deaths in the United States (953,110 lives) were caused by a cardiovascular disease, and cancer caused 539,377 deaths (americanheart.org). More than a million Americans are expected to have a heart attack a year, while cancer strikes one in two men and one in three women (Landis, 1998). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and means relating to atherosclerosis Inventor(s): Petyaev, Ivan; (Cambridge, GB) Correspondence: NIXON & VANDERHYE P.C.; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201; US Patent Application Number: 20030194746 Date filed: August 22, 2002 Abstract: The present invention relates to the identification of lipid oxidising antibodies as a key pathogenic factor in atherosclerotic disorders. The presence of such antibodies is a important marker for the diagnosis and prognosis of such disorders and methods and means for the assessment of athersclerotic conditions are provided herein.
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Excerpt(s): The present invention relates to methods for assessing and treating atherosclerosis and related conditions in an individual. Methods of the present invention are useful in the clinical diagnosis, prognosis, prophylaxis and therapy of atherosclerosis and related disorders. Auto-antibodies against such lipids as cholesterol [Swartz G. M., Jr., et al Proc. Natl. Acad. Sci. USA (1988), 85, 1902-1906, Alving C. R. and Swartz G. M., Jr. Critical Reviews in Immunology (1991), 10, 441-453.], phospholipids [Alving C. R. Biochem. Soc. Trans. (1984), 12, 342-344.] and low density lipoproteins (LDL) are found in human plasma (Kabakov A. E. et al Clin. Immun. Immunopath. (1992), 63, 214-220, Mironova M et al Ibid. (1997), 85, 73-82.] and are involved in the development of atherosclerosis [Lopes-Virella M. F. and Virella G. Clin. Immun. Immunopath. (1994), 73, 155-167, Kiener P. A. et al Arterioscler. Thromb Vasc. Biol. (1995), 15, 990-999.]. Separately, neither antibodies nor LDL are a pathogenic factor, only the immune complex of the two [Tertov V. V et al Atherosclerosis (1990), 81, 183-189, Orekhov A. N. et al Biochem. Biophys. Res. Comm. (1989), 162, 206-211.]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods fo treating conditions associated with insulin resistance with aicar, (5amino-4-imidazole carboxamide riboside) and related compounds Inventor(s): Ido, Yasuo; (Brookline, MA), Kraegen, Edward W; (Sydney, AU), Ruderman, Neil; (Newton, MA) Correspondence: WEINGARTEN, SCHURGIN, GAGNEBIN & LEBOVICI LLP; TEN POST OFFICE SQUARE; BOSTON; MA; 02109; US Patent Application Number: 20030212014 Date filed: March 12, 2003 Abstract: The long-term usage of AICR (5-aminio, 4-imidazole carboxamide riboside) to produce sustained metabolic and biological changes in mammals that overcome insulin resistance, i.e., increase insulin sensitivity, and result in benefits in diseases and conditions such as diabetes, hypertension, atherosclerosis, polycystic ovary syndrome and gallstones is described long-term usage of AICAR, particularly intermittent administration, e.g., three days per week, appears to have some of the positive effects of exercise, having an impact on the amount Of food consumed by a subject and resulting in reduced fat build-up and increase in muscle mass. Therefore, AICAR administration has a positive impact in reducing obesity. AICAR can also Prove useful in preventing or treating vascular diseases associated with hyperglycemia, high plasma levels of free fatty acids (FFA) and triglyceride, and insulin resistance by virtue of the fact that this agent activates fatty acid oxidation. Animal tests have Shown that chronic intermittent treatment with AICAR has not resulted in any noticeable toxic effects. AICAR and related compounds are activators of AMP-activated protein kinase (AMPK) and, furthermore, are effective at decreasing malonyl CoA levels in the animal. Excerpt(s): This application claims the priority of the following applications: U.S. Provisional Application No. 60/222,131, filed Jul. 31, 2000 entitled, USE OF AICAR (5AMINO-4-IMIDAZOLE CARBOXAMIDE RIBOSIDE) AND RELATED COMPOUNDS TO TREAT INSULIN RESISTANCE; International Application No. PCT/US00/40607, filed Aug. 9, 2000 entitled, METHOD OF MAINTAINING VASCULAR INTEGRITY USING AICAR (5-AMINO-4-IMIDAZOLE CARBOXAMIDE RIBOSIDE) AND RELATED COMPOUNDS; and International Application No. PCT/US01/18467 filed Jun. 6, 2001 entitled, USE OF AICAR (5-AMINO-4-IMIDAZOLE CARBOXAMIDE RIBOSIDE) AND RELATED COMPOUNDS FOR THE PREVENTION AND
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TREATMENT OF OBESITY, the whole of which are hereby incorporated by reference herein. AMP-activated protein kinase (AMPK) is a cytoplasmic enzyme that has been shown to exist in both the liver and skeletal muscle. As its name indicates, AMPK is activated by increasing levels of AMP and, secondarily, by an increase in the ratio of AMP to ATP in the cell. AMP levels rise in the cell as ATP is hydrolyzed to ADP and Pi. Two molecules of ADP, through the action of myokinase, also known as adenylate kinase, produce one molecule of ATP and one molecule of AMP. In addition to its activation by AMP, AMPK is activated through phosphorylation by an upstream kinase called AMPK kinase (AMPKK). AMP also allosterically activates AMPKK. Phosphorylation of AMPK by AMPKK makes it a poor substrate for phosphatases. All these factors combined together make AMPK very sensitive to minimal fluctuations in cellular AMP levels. AMPK has several known substrates, specifically enzymes that it can phosphorylate and modulate. In the liver, AMPK has been shown to phosphorylate hydroxymethyl glutaryl CoA (HMGCOA) reductase and acetyl CoA carboxylase (ACC), inhibiting the actions of both enzymes. Reducing HMGCOA reductase activity inhibits cholesterol synthesis, and reducing ACC activity decreases the generation of malonyl CoA, an intermediate in fatty acid synthesis. In skeletal muscle, AMPK also is an inhibitor of carnitine palmitoyl transferase I, which regulates the uptake of fatty acids into mitochondria where they are oxidized. In addition, AMPK has been shown to increase glucose transport into the muscle. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for inhibiting diabetic complications Inventor(s): Alderson, Nathan; (West Columbia, SC), Baynes, John W.; (Columbia, SC), Degenhardt, Thorsten P.; (Durham, NC), Hudson, Billy G.; (Lenexa, KS), Khalifah, Raja G.; (Overland Park, KS), Thorpe, Suzanne R.; (Columbia, SC) Correspondence: MCDONNELL BOEHNEN HULBERT & BERGHOFF; 300 SOUTH WACKER DRIVE; SUITE 3200; CHICAGO; IL; 60606; US Patent Application Number: 20030181492 Date filed: January 30, 2003 Abstract: The instant invention provides compositions and methods for modeling postAmadori AGE formation and the identification and characterization of effective inhibitors of post-Amadori AGE formation, and such identified inhibitor compositions. The instant invention also teaches methods to treat or prevent diabetes associated hyperlipidemia, cellular redox imbalances, hypercholesterolemia, hypertriglyceridemia, and atherosclerosis, comprising administering the compounds of the invention to a mammal in need thereof. Excerpt(s): This application is a continuation-in-part of U.S. Patent Applications, serial No. 60/105,182 filed Oct. 22, 1998; Ser. No. 08/971,285 filed Nov. 17, 1997 and Ser. No. 08/711,555, filed Sep. 10, 1996, and claims priority to U.S. Provisional Application for Patent serial No. 60/003,268, filed Sep. 12, 1995, the contents of each of which are hereby incorporated by reference in their entirety. The instant invention is in the field of Advanced Glycation End-products (AGEs), their formation, detection, identification, inhibition, and inhibitors thereof. Nonenzymatic glycation by glucose and other reducing sugars is an important post-translational modification of proteins that has been increasingly implicated in diverse pathologies. Irreversible nonenzymatic glycation and crosslinking through a slow, glucose-induced process may mediate many of the complications associated with diabetes. Chronic hyperglycemia associated with diabetes
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can cause chronic tissue damage which can lead to complications such as retinopathy, nephropathy, and atherosclerotic disease. (Cohen and Ziyadeh, 1996, J. Amer. Soc. Nephrol. 7:183-190). It has been shown that the resulting chronic tissue damage associated with long-term diabetes mellitus arise in part from in situ immune complex formation by accumulated immunoglobulins and/or antigens bound to long-lived structural proteins that have undergone Advanced Glycosylation End-product (AGE) formation. via non-enzymatic glycosylation (Brownlee et al., 1983, J. Exp. Med. 158:17391744). The primary protein target is thought to be extra-cellular matrix associated collagen. Nonenzymatic glycation of proteins, lipids, and nucleic acids may play an important role in the natural processes of aging. Recently protein advanced glycation has been associated with.beta.-amyloid deposits and formation of neurofibrillary tangles in Alzheimer disease, and possibly other neurodegenerative diseases involving amyloidosis (Colaco and Harrington, 1994, NeuroReport 5: 859-861). Glycated proteins have also been shown to be toxic, antigenic, and capable of triggering cellular injury responses after uptake by specific cellular receptors (see for example, Vlassara, Bucala & Striker, 1994, Lab. Invest. 70:138-151; Vlassara et al., 1994, PNAS(USA) 91:11704-11708; Daniels & Hauser, 1992, Diabetes 41:1415-1421; Brownlee, 1994, Diabetes 43:836-841; Cohen et al., 1994, Kidney Int. 45:1673-1679; Brett et al., 1993, Am. J. Path. 143:1699-1712; and Yan et al., 1994, PNAS(USA) 91:7787-7791). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel 3-substituted urea derivatives and medicinal use thereof Inventor(s): Ishibuchi, Seigo; (Chuo-ku, Tokyo, JP), Itoh, Katsuhiko; (Saitama-shi, Saitama, JP), Naka, Yoichi; (Nakatsu-shi, Ooita, JP), Sumichika, Hiroshi; (Chuo-ku, Tokyo, JP) Correspondence: WENDEROTH, LIND & PONACK, L.L.P.; 2033 K STREET N. W.; SUITE 800; WASHINGTON; DC; 20006-1021; US Patent Application Number: 20030207939 Date filed: February 5, 2003 Abstract: The present invention relates to a urea derivative of the formula (1) 1wherein each symbol is as described in the specification, a pharmaceutically acceptable salt thereof and pharmaceutical use thereof. The compound of the present invention has a C5a receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of diseases or syndromes due to inflammation caused by C5a [e.g., autoimmune diseases such as rheumatism, systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease and serious organ injury (e.g., pneumonia, nephritis, hepatitis, pancreatitis and the like) due to activation of leukocytes caused by ischemia, trauma, burn, surgical invasion and the like]. In addition, it is useful as an agent for the prophylaxis or treatment of infectious diseases caused by bacteria or virus that invades via a C5a receptor. Excerpt(s): The present invention relates to a urea derivative showing a C5a receptor antagonistic action and useful for the prophylaxis or treatment of autoimmune diseases such as rheumatism and systemic lupus erythematosus and the like, sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases such as asthma and the like, atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease or serious organ injuries (e.g., pneumonia, nephritis,
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hepatitis and pancreatitis and the like) due to activation of leukocytes caused by ischemia, trauma, burn, surgical invasion and the like, a pharmaceutically acceptable salt thereof and pharmaceutical use thereof. When the complement system is activated, the protein of the complement system is enzymolysed and fragments having various physiological activities are produced. One of the fragments, complement component C5a, is a glycoprotein having a molecular weight of about 11,000, consists of 74 amino acids and has a strong inflammation inducing action. C5a has a broad range of actions such as smooth muscle contraction, promotion of blood vessel permeability, migration of leukocyte, degranulation of leukocyte, production of reactive oxygen species, reinforcement of antibody production, induction of production of cytokine, TNF (tumor necrosis factor), leukotriene and the like, and the like, and is said to be a causative substance of diseases such as autoimmune diseases (e.g., rheumatism and systemic lupus erythematosus and the like), sepsis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, allergic diseases (e.g., asthma and the like), atherosclerosis, cardiac infarction, brain infarction, psoriasis, Alzheimer's disease, serious organ injuries (e.g., pneumonia, nephritis, hepatitis, pancreatitis and the like) due to activation of leukocytes caused by ischemia, trauma, burn, surgical invasion and the like, and the like [Annu. Rev. Immunol., vol. 12, pp. 775-808 (1994), Immunopharmacology, vol. 38, pp. 3-15 (1997), Curr. Pharm. Des., vol. 5, pp. 737-755 (1999) and IDrugs, vol. 2, pp. 686-693 (1999)]. Accordingly, a non-peptide small molecular compound having a C5a receptor antagonistic action is expected as a novel non-steroid type antiinflammatory drug. In addition, it can be expected as a prophylactic or therapeutic drug of infectious diseases caused by bacteria or virus that invades via a C5a receptor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel indazole peptidomimetics as thrombin receptor antagonists Inventor(s): Maryanoff, Bruce E.; (Forest Grove, PA), Pandey, Anjali; (Fremont, CA), Scarborough, Robert M.; (Half Moon Bay, CA), Zhang, Han-Cheng; (Lansdale, PA) Correspondence: AUDLEY A. CIAMPORCERO JR.; JOHNSON & JOHNSON; ONE JOHNSON & JOHNSON PLAZA; NEW BRUNSWICK; NJ; 08933-7003; US Patent Application Number: 20030199455 Date filed: March 31, 2003 Abstract: The invention is directed to novel indazole peptidomimetic compounds which are useful as thrombin receptor antagonists for the treatment of diseases associated with thrombosis, restenosis, hypertension, heart failure, arrhythmia, inflammation, angina, stroke, atherosclerosis, ischemic conditions, Angiogenesis related disorders, cancer, and neurodegenerative disorders. Pharmaceutical compositions comprising the substituted indazole peptidomimetics of the present invention and methods of treating conditions mediated by the thrombin receptor are also disclosed. Excerpt(s): This invention relates to certain novel thrombin receptor antagonists, their synthesis and their use for the treatment of diseases associated with thrombosis, restenosis, hypertension, heart failure, arrhythmia, inflammation, angina, stroke, atherosclerosis, ischemic conditions, Angiogenesis related disorders, cancer, and neurodegenerative disorders. Thrombin is an important serine protease in hemostasis and thrombosis. One of the key actions of thrombin is cellular modulation via receptor activation. A functional human thrombin receptor (PAR-1), cloned by Coughlin in 1991 (T. -K. Vu, Cell 1991, 64, 1057), was found to be a member of the G-protein coupled
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receptor (GPCR) superfamily. The receptor activation putatively occurs by N-terminal recognition and proteolytic cleavage at the Arg-41/Ser42 peptide bond to reveal a truncated N-terminus. This new receptor sequence, which has an SFLLRN (Ser-Phe-LeuLeu-Arg-Asn) N-terminus acting as a tethered ligand to recognize a site on the receptor, can trigger activation and signal transduction leading to platelet aggregation. Since 1991, three other protease-activated receptors with extensive homology to the thrombin receptor, "PAR-2" (S. Nystedt, Proc. Natl. Acad. Sci USA 1994, 91, 9208), "PAR-3" (H. Ishihara, Nature 1997, 386, 502), and "PAR4" (W. -F. Xu, Proc. Natl. Acad. Sci USA 1998, 95, 6642), have been cloned. Thrombin receptor (PAR-1) specific antibody-induced blockade of the platelet thrombin receptor has shown efficacy against arterial thrombosis in vivo (J. J. Cook Circulation 1995, 91, 2961). Hence, antagonists of the thrombin receptor (PAR-1) are useful to block these protease-activated receptors and, as such, may be used to treat platelet mediated thrombotic disorders such as myocardial infarction, stroke, restenosis, angina, atherosclerosis, and ischemic conditions. The thrombin receptor (PAR-1) has also been identified on other cell types: endothelial, fibroblast, renal, osteosarcoma, smooth muscle, myocytes, tumor, and neuronal/glia. Thrombin activation of endothelial cells upregulates P-selectin to induce polymorphonuclear leukocyte adhesion--an inflammatory response of the vessel wall (Y. Sugama, J. Cell Biol. 1992, 119, 935). In fibroblasts, thrombin receptor (PAR-1) activation induces proliferation and transmission of mitogenic signals (D. T. Hung, J. Cell Biol. 1992, 116, 827). Thrombin has been implicated in osteoblast proliferation through its activation of osteoblast cells (D. N. Tatakis, Biochem. Biophys. Res. Commun. 1991, 174, 181). Thrombin has been implicated in the regulation and retraction of neurons (K. Jalink, J. Cell. Biol. 1992, 118, 411). Therefore, in this context, the antagonist compounds of this invention may also be useful against inflammation, osteoporosis, Angiogenesis related disorders, cancer, neurodegenerative disorders, hypertension, heart failure, arrhythmia, glomerulonephritis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel protein, its production and use Inventor(s): Taniyama, Yoshio; (Ibaraki, JP) Correspondence: TAKEDA PHARMACEUTICALS NORTH AMERICA, INC; INTELLECTUAL PROPERTY DEPARTMENT; 475 HALF DAY ROAD; SUITE 500; LINCOLNSHIRE; IL; 60069; US Patent Application Number: 20030175905 Date filed: December 18, 2002 Abstract: This invention relates to a novel protein having a lecithin-cholesterol acyltransferase-like activity, etc. or its salt, a precursor protein of the protein or its salt, a partial peptide of the protein or its salt; a DNA coding for the protein; a recombinant vector; a transformant; a method for producing the protein, a pharmaceutical composition comprising the protein, the partial peptide or its salt; and an antibody to the protein or the partial peptide. The protein, the partial peptide or its salt, and the DNA are useful as an agent for treating or preventing arteriosclerosis, atherosclerosis, hyperlipidemia, hypercalorism, obesity or hypertriglyceridemia. The antibody can be used in assay of the protein, the partial peptide or its salt. The protein, the partial peptide or its salt is useful as a reagent for the screening for candidate medical compounds.
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Excerpt(s): The present invention relates to a novel protein having a lecithin-cholesterol acyltransferase-like activity etc. and a DNA coding for the protein. Cholesterol is an important lipid constituting the animal cell membrane and defining its character. Moreover, it is a precursor of steroid hormones, thus being a substance essential to animal life. However, due to the recent changes in dietary habit and ecology, arteriosclerosis and other adult diseases arising from pathological intracellular accumulation of cholesterol are now presenting a serious problem so that elucidation of the mechanisms of cholesterol metabolism in the body is being awaited. In the efflux of cholesterol from the peripheral cells, high density lipoprotein (hereinafter sometimes referred to briefly as HDL) is suspected to play a cardinal role and this assumption has been supported by the epidemiologic finding of an inverse correlation between risk for coronary artery disease and plasma HDL levels and the experimental finding that HDL in culture medium stimulates cholesterol efflux from cells and decreases the intracellular concentration of cholesterol (Journal of Lipid Research, 37, 2473, 1996). In the reverse cholesterol transport system, lecithin-cholesterol acyltransferase (hereinafter sometimes referred to briefly as LCAT) is involved to a significant extent. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Orally administered peptides to ameliorate atherosclerosis Inventor(s): Anantharamaiah, Gattadahalli M.; (Birmingham, AL), Fogelman, Alan M.; (Beverly Hills, CA), Navab, Mohamad; (Los Angeles, CA) Correspondence: QUINE INTELLECTUAL PROPERTY LAW GROUP, P.C.; P O BOX 458; ALAMEDA; CA; 94501; US Patent Application Number: 20030171277 Date filed: June 28, 2002 Abstract: This invention provides novel peptides that ameliorate one or more symptoms of atherosclerosis. The peptides are highly stable and readily administered via an oral route. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/896,841, filed on Jun. 29, 2001, which is a continuation-in-part of U.S. Ser. No. 09/645,454, filed on Aug. 24, 2000, both of which are incorporated herein by reference in their entirety for all purposes. This invention relates to the field of atherosclerosis. In particular, this invention pertains to the identification of a class of peptides that are orally administrable and that ameliorate one or more symptoms of atherosclerosis. Cardiovascular disease is a leading cause of morbidity and mortality, particularly in the United States and in Western European countries. Several causative factors are implicated in the development of cardiovascular disease including hereditary predisposition to the disease, gender, lifestyle factors such as smoking and diet, age, hypertension, and hyperlipidemia, including hypercholesterolemia. Several of these factors, particularly hyperlipidemia, and hypercholesteremia (high blood cholesterol concentrations) provide a significant risk factor associated with atherosclerosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pharmacotherapy for vascular dysfuntion associated with deficient nitric oxide bioactivity Inventor(s): Gross, Steven S.; (New York, NY), Jones, Caroline L.; (London, GB) Correspondence: Eric S Spector; Jones Tullar & Cooper; Eads Station; PO Box 2266; Arlington; VA; 22202; US Patent Application Number: 20030212135 Date filed: October 9, 2002 Abstract: A patient with a disorder involving endothelial dysfunction associated with deficient nitric oxide bioactivity, e.g., coronary artery disease, atherosclerosis, hypertension, diabetes or neurodegenerative condition stemming from ischemia and/or inflammation, is treated by administering nitric oxide bioactivity increasing hydroxyguanidine. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/196,298, filed Apr. 12, 2000. This invention is directed at enhancing vascular function in patients with vascular diseases and conditions that are associated with deficient nitric oxide bioactivity, endothelial dysfunction, tetrahydrobiopterin insufficiency and/or oxidative stress. In an embodiment the oxidative stress triggers the tetrahydrobiopterin insufficiency which in turn triggers deficient nitric oxide bioactivity and endothelial dysfunction, and the invention is directed at treating the vascular diseases and conditions associated with the endothelial dysfunction. It is known that nitric oxide is constitutively produced by vascular endothelial cells where it plays a key physiological role in the moment-to-moment regulation of blood pressure and vascular tone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Processes and intermediates for preparing glycogen phosphorylase inhibitors Inventor(s): Barrila, Mark T.; (East Lyme, CT), Busch, Frank R.; (Gales Ferry, CT), Couturier, Michel A.; (Pawcatuck, CT), Orrill, Susan L.; (Gales Ferry, CT), Rose, Peter R.; (Ledyard, CT), Tickner, Derek L.; (Waterford, CT), Tobiassen, Harry O; (Ledyard, CT), Withbroe, Gregory J.; (Gales Ferry, CT) Correspondence: PFIZER INC.; PATENT DEPARTMENT, MS8260-1611; EASTERN POINT ROAD; GROTON; CT; 06340; US Patent Application Number: 20030187051 Date filed: January 16, 2003 Abstract: The instant invention provides novel processes and intermediates useful in the preparation of certain N-(indole-2-carbonyl)-.beta.-alaninamide compounds, which compounds are glycogen phosphorylase inhibitors useful in the treatment of diseases such as hypercholesterolemia, hyperglycemia, hyperinsulinemia, hyperlipidemia, hypertension, atherosclerosis, diabetes, diabetic cardiomyopathy, infection, tissue ischemia, myocardial ischemia, and in inhibiting tumor growth. Excerpt(s): The instant invention provides novel processes and intermediates useful in the preparation of certain N-(indole-2-carbonyl)-.beta.-alanina- mide compounds, which compounds are glycogen phosphorylase inhibitors useful in the treatment of diseases such as hypercholesterolemia, hyperglycemia, hyperinsulinemia, hyperlipidemia, hypertension, atherosclerosis, diabetes, diabetic cardiomyopathy, infection, tissue ischemia, myocardial ischemia, and in inhibiting tumor growth. Despite the early
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discovery of insulin and its subsequent widespread use in the treatment of diabetes, and the later discovery of, and use of, sulfonylureas (e.g. Chlorpropamide.TM. (Pfizer), Tolbutamide.TM. (Upjohn), Acetohexamide.TM. (E. I. Lilly), Tolazamide.TM. (Upjohn), and biguanides (e.g. Phenformin.TM. (Ciba Geigy), and Mefformin.TM. (G. D. Searle)) as oral hypoglycemic agents, therapeutic regimens for the treatment of diabetes remain less than satisfactory. The use of insulin, necessary in about 10% of diabetic patients in which synthetic hypoglycemic agents are not effective (Type 1 diabetes, insulin dependent diabetes mellitus), requires multiple daily doses, usually by self-injection. Determination of the proper dosage of insulin requires frequent estimations of sugar levels in the urine or blood. The administration of an excess dose of insulin causes hypoglycemia, with effects ranging from mild abnormalities in blood glucose to coma, or even death. Treatment of non-insulin dependent diabetes mellitus (Type 2 diabetes) usually consists of a combination of diet, exercise, oral agents, e.g., sulfonylureas, and, in more severe cases, insulin. However, clinically available hypoglycemic agents can have other side effects that limit their use. In any event, where one of these agents may fail in an individual case, another may succeed. A continuing need for hypoglycemic agents, which may have fewer side effects or succeed where others fail, is clearly evident. Atherosclerosis, a disease of the arteries, is recognized to be the leading cause of death in the United States and Western Europe. The pathological sequence leading to atherosclerotic development and occlusive heart disease is well known. The earliest stage in this sequence is the formation of "fatty streaks" in the carotid, coronary, and cerebral arteries, and in the aorta. These lesions are yellow in color due to the presence of lipid deposits found principally within smooth-muscle cells and in macrophages of the intima layer of the arteries and aorta. It is further postulated that most of the cholesterol found within the fatty streaks, in turn, gives rise to development of the socalled "fibrous plaque", which consists of accumulated intimal smooth muscle cells laden with lipid and surrounded by extra-cellular lipid, collagen, elastin, and proteoglycans. These cells, plus matrix, form a fibrous cap that covers a deeper deposit of cell debris and more extra cellular lipid, which comprises primarily free and esterified cholesterol. The fibrous plaque forms slowly, and is likely in time to become calcified and necrotic, advancing to the so-called "complicated lesion" which accounts for the arterial occlusion and tendency toward mural thrombosis and arterial muscle spasm that characterize advanced atherosclerosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Promoting whole body health Inventor(s): Doyle, Matthew Joseph; (US), Glandorf, William Michael; (Mason, OH), Hunter-Rinderle, Stephen Joseph; (Mason, OH), White, Donald James JR.; (Fairfield, OH) Correspondence: THE PROCTER & GAMBLE COMPANY; INTELLECTUAL PROPERTY DIVISION; WINTON HILL TECHNICAL CENTER - BOX 161; 6110 CENTER HILL AVENUE; CINCINNATI; OH; 45224; US Patent Application Number: 20030206874 Date filed: June 5, 2003 Abstract: The present invention relates to promoting whole body health in humans and animals by using topical oral compositions comprising an antimicrobial agent, in particular stannous salts, such as stannous fluoride and stannous chloride in combination with a polymeric mineral surface active agent such as condensed
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polyphosphates or polyphosphonates. In addition to providing a spectrum of intraoral benefits, topical administration of the present compositions to the oral cavity surprisingly provides benefits to systemic health. In particular, the present invention relates to methods of using the present topical oral compositions to reduce the risk in development of cardiovascular disease, stroke, atherosclerosis, diabetes, severe respiratory infections, premature births and low birth weight, post-partum dysfunction in neurologic and developmental functions, and associated increased risk of mortality. Excerpt(s): This application is a continuation-in-part of application Ser. No. 09/607,240, filed Jun. 30, 2000; application Ser. No. 09/710, 440 filed Nov. 10, 2000; and application Ser. No. 10/039,620, filed Oct. 24, 2001, which is a divisional of U.S. application Ser. No. 09/451,420 filed Nov. 30, 1999, which is a continuation-in-part of application Ser. No. 09/203,216, filed Nov. 30, 1998, abandoned, which is a continuation-in-part of application Ser. No. 08/754,577, filed Nov. 21, 1996, now U.S. Pat. No. 5,939,052, all herein incorporated by reference. The present invention relates to promoting and enhancing whole body health or overall systemic health in humans and other animals, by use of topical oral compositions comprising an antimicrobial agent, in particular stannous salts, such as stannous fluoride and stannous chloride in combination with a polymeric mineral surface active agent such as condensed polyphosphates or polyphosphonates. In addition to providing a spectrum of intraoral benefits including control of breath malodor, control of dental plaque growth and metabolism, reduced gingivitis, decreased progression to periodontal disease, reductions in dentinal hypersensitivity and reduced coronal and root dental caries, topical administration of the present compositions to the oral cavity surprisingly provides benefits to systemic health. In particular, the present invention relates to methods of using the present topical oral compositions to reduce the risk in development of cardiovascular disease, stroke, atherosclerosis, diabetes, severe respiratory infections, premature births and low birth weight, post-partum dysfunction in neurologic and developmental functions, and associated increased risk of mortality. Recent research has revealed that periodontal disease or gum disease may be a far more serious threat to overall systemic health than previously realized. Periodontitis, a common form of periodontal disease, is a tissue destructive process resulting from the accumulation of pathogenic bacteria along the gingival margin and the consequent tissue destructive host response to these pathogens. The presence of periodontitis can result in the release of bacterial pathogens and/or bacterial toxins into the bloodstream. The host responses to the presence of these bacterial pathogens and/or toxins in the bloodstream may contribute to the development of atherosclerosis (heart disease), increase the risk of premature, underweight babies; and pose a serious threat to people whose health is compromised by diabetes, respiratory diseases, stroke and bacteremia bacteria in the blood). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Quinolinyl and benzothiazolyl modulators Inventor(s): Furukawa, Noboru; (Osaka, JP), Hagiwara, Atsushi; (Osaka, JP), Houze, Jonathan B.; (San Mateo, CA), McGee, Lawrence R.; (Pacifica, CA), Rubenstein, Steven M.; (Pacifica, CA), Shinkai, Hisashi; (Osaka, JP) Correspondence: TOWNSEND AND TOWNSEND AND CREW, LLP; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20030171399 Date filed: October 21, 2002
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Abstract: Compounds, compositions and methods are provided that are useful in the treatment or prevention of a condition or disorder mediated by PPAR.gamma. In particular, the compounds of the invention modulate the function of PPAR.gamma. The subject methods are particularly useful in the treatment and/or prevention of diabetes, obesity, hypercholesterolemia, rheumatoid arthritis and atherosclerosis. Excerpt(s): This application claims the benefit of U.S. provisional application Ser. No. 60/214,810, filed Jun. 28, 2000, and is related to U.S. Patent Application No. 60/073,042, filed Jan. 29, 1998, and U.S. patent application Ser. No. 09/234,327, filed Jan. 20, 1999, now U.S. Pat. No. 6,200,995. This application is further related to U.S. Patent Application No. 60/141,672, filed Jun. 30, 1999, U.S. patent application Ser. No. 09/606,433, filed Jun. 28, 2000 and PCT Application No. US 00/18178, filed Jun. 28, 2000, now PCT Publication No. WO 01/00579, the disclosures of each of the above being incorporated herein by reference in their entirety. The present invention relates to compounds that modulate the PPAR.gamma. receptor and are useful in the diagnosis and treatment of type II diabetes (and complications thereof), hypercholesterolemia (and related disorders associated with abnormally high or low plasma lipoprotein or triglyceride levels) and inflammatory disorders. The peroxisome proliferator-activated receptors (PPARs) are transducer proteins belonging to the steroid/thyroid/retinoid receptor superfamily. The PPARs were originally identified as orphan receptors, without known ligands, but were named for their ability to mediate the pleiotropic effects of fatty acid peroxisome proliferators. These receptors function as ligand-regulated transcription factors that control the expression of target genes by binding to their responsive DNA sequence as heterodimers with RXR. The target genes encode enzymes involved in lipid metabolism and differentiation of adipocytes. Accordingly, the discovery of transcription factors involved in controlling lipid metabolism has provided insight into regulation of energy homeostasis in vertebrates, and further provided targets for the development of therapeutic agents for disorders such as obesity, diabetes and dyslipidemia. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substituted N-Aliphatic-N-Aromatictertiary-Heteroalkylamines useful for inhibiting cholesteryl ester transfer protein activity Inventor(s): Durley, Richard C.; (Chesterfield, MO), Grapperhaus, Margaret L.; (Troy, IL), Mischke, Deborah A.; (Defiance, MO), Parnas, Barry L.; (University City, MO), Reinhard, Emily J.; (Chesterfield, MO), Rueppel, Melvin L.; (St. Louis, MO), Sikorski, James A.; (Des Peres, MO) Correspondence: Pharmacia Corporation; Corporate Patent Department; 800 N. Lindbergh Blvd.; Mail Zone O4E; St. Louis; MO; 63167; US Patent Application Number: 20030191306 Date filed: December 16, 2002 Abstract: The invention relates to substituted N-Aliphatic-N-Aromatic tertiaryHeteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis, dyslipidemia, and other coronary artery disease. Excerpt(s): This invention is in the field of treating cardiovascular disease, and specifically relates to compounds, compositions and methods for treating atherosclerosis and other coronary artery disease. More particularly, the invention relates to substituted N-Aliphatic-N-Aromatictertiary-Heteroalkylamine compounds
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that inhibit cholesteryl ester transfer protein (CETP), also known as plasma lipid transfer protein-I. Numerous studies have demonstrated that a low plasma concentration of high density lipoprotein (HDL) cholesterol is a powerful risk factor for the development of atherosclerosis (Barter and Rye, Atherosclerosis, 121, 1-12 (1996)). HDL is one of the major classes of lipoproteins that function in the transport of lipids through the blood. The major lipids found associated with HDL include cholesterol, cholesteryl ester, triglycerides, phospholipids and fatty acids. The other classes of lipoproteins found in the blood are low density lipoprotein (LDL) and very low density lipoprotein (VLDL). Since low levels of HDL cholesterol increase the risk of atherosclerosis, methods for elevating plasma HDL cholesterol would be therapeutically beneficial for the treatment of atherosclerosis and other diseases associated with accumulation of lipid in the blood vessels. These diseases include, but are not limited to, coronary heart disease, peripheral vascular disease, and stroke. Atherosclerosis underlies most coronary artery disease (CAD), a major cause of morbidity and mortality in modern society. High LDL cholesterol (above 180 mg/dl) and low HDL cholesterol (below 35 mg/dl) have been shown to be important contributors to the development of atherosclerosis. Other diseases, such as peripheral vascular disease, stroke, and hypercholesterolaemia are negatively affected by adverse HDL/LDL ratios. Inhibition of CETP by the subject compounds is shown to effectively modify plasma HDL/LDL ratios, and to check the progress and/or formation of these diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substituted oxindole derivatives as tyrosine kinase inhibitors Inventor(s): Hunter, Robert N; (Durham, NC), Kuyper, Lee Frederick; (Durham, NC), Lackey, Karen Elizabeth; (Durham, NC), Luzzio, Michael J.; (Noank, CT), Dickerson, Scott Howard; (Durham, NC) Correspondence: DAVID J LEVY, CORPORATE INTELLECTUAL PROPERTY; GLAXOSMITHKLINE; FIVE MOORE DR., PO BOX 13398; RESEARCH TRIANGLE PARK; NC; 27709-3398; US Patent Application Number: 20030195234 Date filed: February 27, 2003 Abstract: The present invention is related to oxindole derivatives of structure (I), compositions containing the same, and methods of use and manufacture of the same. Such compounds generally are useful pharmacologically as agents in those disease states alleviated by the alteration of mitogen activated signaling pathways in general, and in particular in the inhibition or antagonism of protein kinases, which pathologically involve aberrant cellular proliferation. Such disease states include tumor growth, restenosis, atherosclerosis, pain and thrombosis, In particular, the present invention relates to a series of substituted oxindole compounds, which exhihit Trk family protein tyrosine kinase inhibition, and which are useful in cancer therapy and chronic pain indications. Excerpt(s): The present invention is related to oxindole derivatives, compositions containing the same, and methods of use and manufacture of the same. Such compounds generally are useful pharmacologically as agents in those disease states alleviated by the alteration of mitogen activated signaling pathways in general, and in particular in the inhibition or antagonism of protein kinases, which pathologically involve aberrant cellular proliferation. Such disease states include tumor growth, restenosis, atherosclerosis, pain and thrombosis. In particular, the present invention
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relates to a series of substituted oxindole compounds, which exhibit Trk family protein tyrosine kinase inhibition, and which are useful in cancer therapy and chronic pain indications. Cell growth, differentiation, metabolism and function are very tightly controlled in higher eukaryotes. The ability of a cell to rapidly and appropriately respond to the array of external and internal signals it continually receives is of critical importance in maintaining a balance between these processes (Rozengurt, Current Opinion in Cell Biology 1992, 4, 161-5; Wilks, Progress in Growth Factor Research 1990, 2, 97-111). The loss of control over cellular regulation can often lead to aberrant cell function or death, often resulting in a disease state in the parent organism. The protein kinases represent a large family of proteins which play a central role in the regulation of a wide variety of cellular processes and maintaining control over cellular function (Hanks, et al., Science 1988, 241, 42-52). A partial list of such kinases includes ab1, ATK, bcr-ab1, Blk, Brk, Btk, c-kit, c-met, c-src, CDK1, CDK2, CDK4, CDK6, cRaf1, CSF1R, CSK, EGFR, ErbB2, ErbB3, ErbB4, ERK, Fak, fes, FGFR1, FGFR2, FGFR3, FGFR4, FGFR5, Fgr, FLK-4, flt-1, Fps, Frk, Fyn, Hck, IGF-1R, INS-R, Jak, KDR, Lck, Lyn, MEK, p38, PDGFR, PIK, PKC, PYK2, ros, tie.sub.1, tie.sub.2, TRK,Yes, and Zap70. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Sulfonylaminocarboxylic acid N-arylamides as guanylate cyclase activators Inventor(s): Schindler, Ursula; (Bad Soden, DE), Schoenafinger, Karl; (Alzenau, DE), Strobel, Hartmut; (Liederbach, DE) Correspondence: FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER; LLP; 1300 I STREET, NW; WASHINGTON; DC; 20005; US Patent Application Number: 20030171352 Date filed: January 24, 2003 Abstract: The present invention relates to compounds of the formula I 1in which A.sup.1, A.sup.2, R.sup.2 and R.sup.3 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds for the therapy and prophylaxis of diseases, for example of cardiovascular disorders such as high blood pressure, angina pectoris, cardiac insufficiency, thromboses or atherosclerosis. The compounds of the formula I have the ability to modulate the endogenous production of cyclic guanosine monophosphate (cGMP) and are generally suitable for the therapy and prophylaxis of disease states which are associated with a disturbed cGMP balance. The invention relates to the use of compounds of the formula I for the therapy and prophylaxis of the designated disease states and for the production of pharmaceuticals therefor, novel compounds of the formula I, pharmaceutical preparations comprising them and processes for their preparation. Excerpt(s): in which A.sup.1, A.sup.2, R.sup.2 and R.sup.3 have the meanings indicated below, which are valuable pharmaceutical active compounds for the therapy and prophylaxis of diseases, for example of cardiovascular disorders such as high blood pressure, angina pectoris, cardiac insufficiency, thromboses or atherosclerosis. The compounds of the formula I have the ability to modulate the endogenous production of cyclic guanosine monophosphate (cGMP) and are generally suitable for the therapy and prophylaxis of disease states which are associated with a disturbed cGMP balance. The invention relates to the use of compounds of the formula I for the therapy and prophylaxis of the designated disease states and for the production of pharmaceuticals therefor, novel compounds of the formula I, pharmaceutical preparations comprising them and processes for their preparation. cGMP is an important intracellular messenger,
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which elicits a number of pharmacological effects by means of the modulation of cGMPdependent protein kinases, phosphodiesterases and ion channels. Examples are smooth muscle relaxation, the inhibition of platelet activation and the inhibition of smooth muscle cell proliferation and leukocyte adhesion. cGMP is produced by particulate and soluble guanylate cyclases as a response to a number of extracellular and intracellular stimuli. In the case of the particulate guanylate cyclases, the stimulation essentially takes place by means of peptidic messenger substances, such as the atrial natriuretic peptide or the cerebral natriuretic peptide. The soluble guanylate cyclases (sGC), which are cytosolic, heterodimeric heme proteins, however, are essentially regulated by a family of low molecular weight, enzymatically formed factors. The most important stimulant is nitrogen monoxide (NO) or a closely relates species. The importance of other factors such as carbon monoxide or the hydroxyl radical is still largely unclarified. The binding of NO to the heme with formation of a pentacoordinated heme-nitrosyl complex is discussed as an activation mechanism of activation by NO. The release associated therewith of the histidine which is bound to the iron in the basal state converts the enzyme into the activated conformation. Active soluble guanylate cyclases are each composed of one.alpha.- and one.beta.-subunit. Several subtypes of the subunits have been described, which differ from one another with respect to sequence, tissue-specific distribution and expression in various stages of development. The subtypes.alpha.sub.1 and.beta.sub.1 are mainly expressed in the brain and lung, while.beta.sub.2 is especially found in liver and kidney. The subtype.alpha.sub.2 was detected in human fetal brain. The subunits designated as.alpha.sub.3 and.beta.sub.3 were isolated from human brain and are homologous to.alpha.sub.1 and.beta.sub.1. More recent studies point to an.alpha.sub.2i subunit, which contains an insert in the catalytic domain. All subunits show great homology in the area of the catalytic domain. The enzymes presumably contain one heme per heterodimer, which is bonded via.beta.sub.1-Cys-78 and/or.beta.sub.1-His-105 and is part of the regulatory center. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Thrombin receptor antagonists Inventor(s): Chackalamannil, Samuel; (East Brunswick, NJ), Chelliah, Mariappan V.; (Edison, NJ), Clasby, Martin C.; (Plainsboro, NJ), Xia, Yan; (Edison, NJ) Correspondence: SCHERING-PLOUGH CORPORATION; PATENT DEPARTMENT (K6-1, 1990); 2000 GALLOPING HILL ROAD; KENILWORTH; NJ; 07033-0530; US Patent Application Number: 20030203927 Date filed: October 16, 2002 Abstract: Heterocyclic-substituted tricyclics of the formula 1or a pharmaceutically acceptable salts thereof, wherein:n.sub.1 and n.sub.2 are independently 0-2;Het is an optionally substituted mono-, bi- or tricyclic heteroaromatic group;B is alkyl or optionally substituted alkenyl;R.sup.22 is --COR.sup.23 or a carboxy, sulfinyl, sulfonyl, sulfonamide or amino acid derivative;R.sup.23 is haloalkyl; alkenyl; haloalkenyl; alkynyl; optionally substituted cycloalkyl; cycloalkyl-alkyl; aryl; arylalkyl; heteroaryl; heterocycloalkyl; or --COOH and/or --SO.sub.3H substituted alkyl;R.sup.1, R.sup.2, R.sup.3, R.sup.9, R.sup.10 and R.sup.11 are as defined in the specification;are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds.
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Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/330,359, filed Oct. 18, 2001. Thrombin is known to have a variety of activities in different cell types and thrombin receptors are known to be present in such cell types as human platelets, vascular smooth muscle cells, endothelial cells and fibroblasts. It is therefore expected that thrombin receptor antagonists will be useful in the treatment of thrombotic, inflammatory, atherosclerotic and fibroproliferative disorders, as well as other disorders in which thrombin and its receptor play a pathological role. Thrombin receptor antagonist peptides have been identified based on structure-activity studies involving substitutions of amino acids on thrombin receptors. In Bernatowicz et al, J. Med. Chem., 39 (1996), p. 4879-4887, tetra- and pentapeptides are disclosed as being potent thrombin receptor antagonists, for example N-trans-cinnamoyl-p-fluoroPhe-- pguanidinoPhe-Leu-Arg-NH.sub.2 and N-trans-cinnamoyl-p-fluoroPhe-p-guanidinoPhe-Leu-Arg-Arg-NH.sub.2. Peptide thrombin receptor anatgonists are also disclosed in WO 94/03479, published Feb. 17, 1994. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Treatment of post-angioplasty restenosis and atherosclerosis with Ras antagonists Inventor(s): George, Jakob; (Tel Aviv-Yafo, IL), Keren, Gad; (Kiryat Ono, IL), Kloog, Yoel; (Herzlia, IL) Correspondence: LERNER, DAVID, LITTENBERG,; KRUMHOLZ & MENTLIK; 600 SOUTH AVENUE WEST; WESTFIELD; NJ; 07090; US Patent Application Number: 20030203942 Date filed: April 22, 2003 Abstract: Disclosed are methods for inhibiting Ras activity such as cell proliferation associated with vascular injury such as post-angioplasty restenosis and atherosclerosis. Preferred Ras antagonists are S-trans-trans farnesylthiosalicylic acid (FTS) and structurally related compounds (or analogs) thereof. Excerpt(s): This application is a continuation of U.S. application Ser. No. 10/023,545, filed Dec. 18, 2001, which is a continuation-in-part of U.S. application Ser. No. 09/597,332, filed Jun. 19, 2000, which claims priority under 35 U.S.C.sctn. 119(e) from U.S. Application No. 60/140,192, filed Jun. 18, 1999. The contents of these two applications are hereby incorporated herein by reference in their entireties. The present invention relates to the inhibition of the onset of or the treatment of non-malignant diseases, and particularly diseases having pathologies involving Ras-induced proliferation of cells. Autoimmune diseases include disorders involving dysfunction of the immune system, which mediates tissue damage. Any organ may be affected by such processes through precipitation of immune complexes, cellular immunity, or inappropriate generation or action of immuno-hormones such as cytokines. Epidemiologically, autoimmune diseases are significant because of the numbers of patients that they affect and the serious morbidity and mortality that they cause. Common chronic systemic diseases in this group include diabetes mellitus, thyroid disease, rheumatoid arthritis, systemic lupus erythmatosus (SLE), primary antiphospholipid syndrome (APS), and a variety of diseases that affect the central nervous system. Neurological autoimmune diseases include disorders specific to the nervous system such as myasthenia gravis, Lambert Eaton myasthenic syndrome, Guillain-Barre syndrome, polymyositis, and multiple sclerosis. In addition, there are neurological complications of the systemic autoimmune diseases. Factors predisposing to autoimmune diseases include genetic predisposition and environmental agents such
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as certain infections and pharmaceutical products. Such factors result in pathological activation of the immune response in susceptible individuals, which is generally controlled by T lymphocytes (T cells). The activation of T cells and B subtypes, involves a complex interaction of cell surface receptors resulting in equally complex signal transduction pathways which eventually affect gene regulation. Full activation of lymphocytes requires parallel stimulation of several signal transduction pathways. See Ohtsuka et al., Biochim. Biophys. Acta. 1310:223-232 (1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of pro-apoptotic factors in treatment of atherosclerosis Inventor(s): Arvelo, Maria B.; (Quincy, MA), Ferran, Christiane; (West Roxbury, MA) Correspondence: CLARK & ELBING LLP; 101 FEDERAL STREET; BOSTON; MA; 02110; US Patent Application Number: 20030207838 Date filed: June 13, 2003 Abstract: The present invention features a novel method of treating vascular disease that involves modifying smooth muscle cells to express a gene encoding a protein having both anti-inflammatory and pro-apoptotic activity. Preferably, the protein of the invention also has an anti-proliferative effect in smooth muscle cells. In general, the method is useful in preparing vascularized organs and vessels for transplant into a patient. Alternatively, the present invention can be applied to treat atherosclerotic lesions in damaged vessels. Excerpt(s): The present application claims benefit to Provisional application No. 60/177,535 filed Jan. 21, 2000, the entire contents of which are incorporated herein by reference. The present invention relates to the field of vascular disease. Vascular disease is the most common cause of morbidity and mortality in the western world, surpassing any other single degenerative disease. The fundamental pathology of vascular disease is an abnormal accumulation of cells within the subintimal space below the surface of the endothelial cell lining, resulting in a decrease in lumen size and tissue perfusion. This accumulation is due to the proliferation and/or migration of smooth muscle cells, and/or inflammatory cells into the intimal layer of a vessel, resulting in restricted blood flow through that vessel, i.e. neointimal occlusive lesions. 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 atherosclerosis, 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 “atherosclerosis” (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 atherosclerosis.
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You can also use this procedure to view pending patent applications concerning atherosclerosis. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON ATHEROSCLEROSIS Overview This chapter provides bibliographic book references relating to atherosclerosis. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on atherosclerosis 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 “atherosclerosis” (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 atherosclerosis: •
Type I Diabetes: Etiology and Treatment Source: Totowa, NJ: Humana Press. 2003. 608 p. Contact: Available from Humana Press. 999 Riverview Drive, Suite 208, Totowa, NJ 07512. (973) 256-1699. Fax (973) 256-8341. E-mail:
[email protected]. Website: www.humanapress.com. PRICE: $130.50; plus shipping and handling. ISBN: 896039315. Summary: The increasing incidence of diabetes worldwide has prompted a rapid growth in the pace of scientific discovery and clinical understanding of this disease. In this book, well-recognized physicians and researchers review the latest thinking about the causes of type 1 diabetes and the best approaches to treating both its acute and chronic complications. The book includes 32 chapters in four sections: etiology (cause), treatment, special management issues, and long-term complications. Specific topics include epidemiology, genetics, prediction and prevention of type 1 diabetes, beta-cell
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destruction by autoimmune processes, the metabolic basis of insulin secretion, prevention and correction of hypoglycemia, nonautoimmune forms of diabetes, diabetic ketoacidosis, insulin regimens, relationship between metabolic control and complications, insulin delivery systems and glucose sensors, patient and family education, nutritional management, management of diabetes in very young children, children, adolescents, hypoglycemia, pregnancy, surgery for the patient with type 1 diabetes, diabetic retinopathy (eye disease), diabetic nephropathy (kidney disease), diabetic peripheral and autonomic neuropathy (nerve disease), the diabetic foot, atherosclerosis in type 1 diabetes, cutaneous (skin) complications, infection and diabetes, pancreas transplantation, islet transplantation, beta cell replacement therapy, and islet growth factors. Each chapter concludes with a list of references and a subject index concludes the textbook. •
Medical Advisor Home Edition: The Complete Guide to Alternative and Conventional Treatments Source: Alexandria, VA: Time-Life Books. 1997. 960 p. Contact: Available from Time-Life Books. 400 Keystone Industrial Park, Dunsmore, PA 18512. PRICE: $20.00. ISBN: 0783552505. Summary: This book offers information about 300 health problems, ranging from relatively benign conditions to serious diseases. The book includes symptom charts that name several related problems and help readers decide which ailment entry to look up. Ailment entries provide a more complete list of symptoms, plus guidelines to discern whether the condition is potentially serious or requires a doctor's attention. Each entry describes the ailment and how it affects the body. Next, the entry outlines the underlying causes of the ailment and the tests and procedures a doctor may use to confirm the diagnosis. The treatment segment presents conventional and alternative recommendations for solving the problem or alleviating the symptoms. Most ailment entries conclude with advice on preventive measures that can be used to maintain health. Alternative treatments described include bodywork, acupuncture and acupressure, herbal therapies, homeopathy, lifestyle changes, and nutrition and diet. The book begins with a section on emergency medicine, and includes a visual diagnostic guide, an atlas to the body, a medicine chest section (describing herbs, homeopathic remedies, and over the counter drugs), a glossary, a subject index, a bibliography, and a list of health associations and organizations. Topics related to diabetes include atherosclerosis, glaucoma, hypoglycemia, kidney disease, obesity, and sexual dysfunction. A section specific to diabetes is also included. The book is illustrated with line drawings and full color photographs.
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Herbal Medicinals: A Clinician's Guide Source: New York, NY: Pharmaceutical Products Press. 1998. 383 p. Contact: Available from Haworth Herbal Press. 10 Alice Street, Binghamton, NY 139041580. (800) HAWORTH. Fax (800) 895-0582. E-mail:
[email protected]. Website: www.haworthpressinc.com. PRICE: $39.95 plus shipping and handling. ISBN: 0789004666. Summary: This book provides information on herbal medicines and nutraceuticals and how they interact with conventional medicines so that clinicians will be aware of issues associated with the concomitant use of herbal and conventional medicines. Topics include the renal implications of herbal remedies; hepatic effects of herbal remedies; and herbal medicines for colds and flu, gastrointestinal problems, rheumatoid arthritis and
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osteoarthritis, diabetes, hypertension, dyslipidemia and atherosclerosis, asthma, anxiety and depression, substance abuse, cancer, dermatologic conditions, and gynecological and obstetric problems. In addition, chapters discuss specific toxicological considerations of selected herbal products and consider the use of herbs from a legal and regulatory perspective. Most chapters use a case based format to provide information on the pharmacology of a particular herb, potential and known interactions, adverse herbal side effects, and effects of the disease state that may affect medication efficacy. 46 tables. Numerous references. •
Levin and O'Neal's the Diabetic Foot. 6th ed Source: St. Louis, MO: Mosby, Inc. 2000. 828 p. Contact: Available from Mosby, Inc. Harcourt Health Sciences, 11830 Westline Industrial Drive, St. Louis, MO 631446-3318. (800) 325-4177 or (314) 872-8370. Fax (314) 432-1380. Website: www.mosby.com. PRICE: $125.00 plus shipping and handling. ISBN: 155664471X. Summary: This book serves as a guide for the interdisciplinary team treating people who have diabetes, focusing on the medical, surgical, psychosocial, and medicolegal aspects of care. The first section explores the foundations of diabetic foot management. Chapters discuss old assumptions and new realities about diabetes, the epidemiology of foot ulcers and amputations, neuropathic problems of the lower extremities, atherosclerosis and thrombosis, the principles and concepts of hemorheology, the biomechanics of the foot in diabetes, cutaneous aspects of diabetes, nutritional issues, and the pathogenesis and management of foot lesions. The section concludes with an overview of diabetic foot care throughout the world. The next section deals with nonsurgical management of diabetic foot problems. Chapters focus on a method for staging and classifying foot lesions, diabetic foot ulcer care, total contact casting, alternative weight redistribution, imaging of the diabetic foot, and noninvasive vascular testing. Other chapter topics include radiologic intervention in diabetic peripheral vascular disease, wound healing, adjunctive hyperbaric oxygen therapy, footwear for injury prevention, Charcot neuroarthropathy of the foot, and infectious problems of the foot. The third section addresses the surgical aspects of diabetic foot care. Chapters discuss the surgical pathology of the foot and clinicopathologic correlations, medical management of diabetic patients during the perioperative period, vascular surgery, plastic surgical reconstruction of the foot, Charcot neuropathy of the foot, lower limb amputation, and rehabilitation of the amputee. The next section is devoted to the team approach to diabetic foot care. Topics include patient education, the role of the wound care nurse and the podiatrist, psychological aspects, and improvements in diabetic foot care. The final section addresses the medicolegal issues relevant to clinicians providing diabetic foot care. Numerous figures. Numerous tables. Numerous references.
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My Doctor Says I Have a Little Diabetes Source: Garden City Park, NY: Avery Publishing Group. 1997. 138 p. Contact: Available from Avery Publishing Group. 120 Old Broadway, Garden City Park, NY 11040. (800) 548-5757 or (516) 741-2155. Fax (516) 742-1892. E-mail:
[email protected]. Website: www.averypublishing.com. PRICE: $9.95 plus shipping and handling. ISBN: 0895298600. Summary: This book, which is written in easy to understand language, serves as a guide to understanding and controlling type 2 diabetes. The book begins with a chapter that provides basic information on diabetes and diabetes care. Topics include the symptoms
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of diabetes, the types of diabetes, risk factors for diabetes, diagnostic tests for diabetes, common misconceptions about diabetes, and the management of the emotional aspects of diabetes. Each of the remaining chapters examines a specific aspect of diabetes care, including monitoring blood levels, following an appropriate diet, exercising, using medications, managing high and low blood glucose levels, preventing complications, and handling special situations. The chapter on glucose monitoring offers guidelines for selecting a monitor and checking blood glucose levels. The chapter on diet presents the latest goals and guidelines for the nutritional management of type 2 diabetes; explains how protein, carbohydrates, fats, and other nutrients affect diabetes; provides meal planning options that will make eating an enjoyable experience; and offers tips for handling special situations. The chapter on exercise discusses some of the advantages of following a program of regular exercise, helps readers choose a program suited to their needs, and offers advice about how to begin an exercise program. The chapter on medication discusses the different diabetes medications, medication interactions and precautions, and the effects that many prescription and over the counter medications have on diabetes. The chapter also presents information about mixing and injecting various types of insulin. The chapter on dealing with high and low blood glucose levels presents the causes, symptoms, and associated problems of hyperglycemia and hypoglycemia. Guidelines for treating these problems are also provided. The chapter on the prevention of complications reviews symptoms and prevention of the complications associated with diabetes, including high blood pressure; atherosclerosis; eye disorders; kidney disease; and foot and lower leg, autonomic nervous system, skin, and sexual problems. The final chapter on special situations covers the special care needed on sick days and when traveling. The book also includes a list of resources and provides tables for converting glucose, cholesterol, and triglyceride levels from milligram per deciliter to millimoles per liter. 3 figures. 8 tables. 28 references. •
Foods That Harm, Foods That Heal: An A-Z Guide to Safe and Healthy Eating Source: Pleasantville, NY: Reader's Digest. 1997. 400 p. Contact: Available from Customer Service, Reader's Digest. Pleasantville, NY 10570. (800) 846-2100. PRICE: $30.00. ISBN: 0895779129. Summary: This nutrition reference book features more than 400 photographs and illustrations with more than 400 A to Z entries on a vast range of foods and health concerns, including caffeine, cancer, diabetes, fast food, garlic, heart disease, influenza, osteoporosis, pregnancy, sexually transmitted diseases, and vegetarianism. The book is designed to help families understand the close links between foods and wellness. Each food entry provides at-a-glance information of its nutrients (or lack of) and its benefits and drawbacks. Each ailment is accompanied by a list of foods and beverages that are considered safe, and what foods or beverages should be cut down or avoided altogether. Case studies help to illustrate various topics. There are special features on eating during different life stages, from infancy to old age, as well as such issues as genetically altered foods, irradiation, pesticides, and pollution. Other topics include how to cook foods to achieve maximum nutritional benefits; which dietary supplements really work; tips on exercise, food storage, and reading food labels; an instructive analysis of the most popular diet regimes; and controversial foods and additives such as eggs, nitrites, bran, cheese, milk, fat, wine, and alcohol. A glossary defines unfamiliar or technical terms; there is also a listing of organizations that can provide further information and resources. Topics specifically related to diabetes include atherosclerosis, basic food groups, blood pressure, carbohydrates, childhood and adolescent nutrition, cholesterol, convenience and fast foods, cravings, diabetes, dieting and weight control, exercise and
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diet to boost energy and lift mood, eye disorders, fats, fiber, heart disease, hypoglycemia, immune system, impotence, indigestion and heartburn, infertility, juicing, kidney diseases, malnutrition and dietary deficiencies, medicine-food interactions, menopause, minerals, neuralgia, obesity, organic foods, osteoporosis, pregnancy, preparation and storage of food, protein, restaurants and eating out, salt and sodium, sleep and diet, smoking and diet, sports nutrition, stress, stroke, sugar and other sweeteners, supplements, traveler's health, vegetarian diets, and vitamins. •
Peripheral Arterial Disease: Diagnosis and Treatment Source: Totowa NJ: Humana Press. 2003. 368 p. Contact: Available from Humana Press. 999 Riverview Drive, Suite 208, Totowa, NJ 07512. (973) 256-1699. Fax (973) 256-8341. E-mail:
[email protected]. Website: www.humanapress.com. PRICE: $89.55. ISBN: 588290522. Summary: This textbook acquaints physicians with all aspects of peripheral arterial disease (PAD), defined as narrowing (stenosis) or blockage (occlusion) within the arteries of the lower extremities. PAD is caused by both modifiable (diabetes, smoking, hypertension) and nonmodifiable (family history, age, gender) factors. Due to the limitations of medical therapy, there is now a special emphasis on prevention of PAD and a special emphasis on risk factors and their treatment. The text includes seventeen chapters: the etiology and pathogenesis of atherosclerosis, the epidemiology and natural history of PAD, clinical evaluation of intermittent claudication, hemodynamics and the vascular laboratory, vascular imaging, chronic critical limb ischemia (lack of blood flow), acute limb ischemia, exercise rehabilitation for intermittent claudication, treatment of risk factors and antiplatelet therapy, pharmacotherapy for intermittent claudication, angiogenesis and gene therapy, endovascular therapy, surgical revascularization, perioperative cardiac evaluation and management for vascular surgery, special consideration for the diabetic foot, arterial vascular disease in women, atheromatous embolism, thromboangiitis obliterans (Buerger's disease), and large-vessel vasculitis. Each chapter concludes with extensive references and a subject index concludes the textbook.
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Endocrinology. 4th ed Source: Philadelphia, PA: Harcourt Health Sciences. 2001. 3 v., 3048 p. Contact: Available from W.B. Saunders. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (314) 453-7010. Fax (800) 568-5136 or (314) 453-7095. E-mail:
[email protected]. Website: customerservice.wbsaunders.com. PRICE: $495.00 plus shipping and handling. ISBN: 0721678408 (three volume set). Summary: This three volume set of books provides a complete, authoritative, up to date analysis of endocrine disease and basic endocrine physiology. This edition consists of 194 chapters that cover every aspect of endocrinology in detail by an authority in the field. About one third of the chapters are new, and the remainder have been rewritten and updated. Topics covered in volume one include the principles of hormone action; neuroendocrinology and the pituitary gland; growth and maturation; immunology and endocrinology; obesity, anorexia nervosa, and nutrition in endocrinology; and diabetes mellitus, carbohydrate metabolism, and lipid disorders. Chapters on diabetes mellitus focus on anatomy and physiology, classification, etiology, diagnosis, and treatment. Specific clinical disorders discussed include syndromes of insulin resistance, oculopathy, neuropathy, nephropathy, diabetic foot complications, ketoacidosis, hyperosmolar coma, lactic acidosis, hypoglycemia, atherosclerosis, syndrome X, and
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hyperglycemia. Volume two includes information on the parathyroid gland, calciotropic hormones, bone metabolism, the thyroid gland, the adrenal gland, and glucocorticoids. Topics covered in volume three include endocrine hypertension and mineralocorticoids, reproductive endocrinology and sexual development, female reproduction, endocrinology of the breast, male reproduction, endocrinology and pregnancy, endocrine tumor syndromes, and endocrine testing and treatment. Numerous figures. Numerous tables. Numerous references. •
Diabetes and Cardiovascular Disease Source: Totowa, NJ: The Humana Press, Inc. 2001. 458 p. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail:
[email protected] PRICE: $125.00, plus shipping and handling. ISBN: 089603755X. Summary: With over ten million diagnosed patients and another five million undiagnosed, diabetes mellitus and its complications is a major public health problem that will assume epidemic proportions as the population grows older. This textbook offers practicing physicians the day to day practical knowledge about cardiovascular disease and diabetes. The 24 chapters in the book focus on either clinical or basic aspects of diabetes and cardiovascular disease. Part I, pathophysiology, reviews the mechanisms and risk factors for diabetic cardiovascular disease. Specific topics include the effects of insulin on the vascular system, vascular abnormalities in the prediabetic state, diabetes and advanced glycation end products, diabetes and hypertension (high blood pressure), the renin-angiotensin system, diabetes and dyslipidemia (disordered levels of fats in the blood), diabetes and thrombosis (blood clotting), diabetes and atherosclerosis (hardening and narrowing of the arteries), and nitric oxide and its role in diabetes mellitus. Part II focuses on the heart in diabetes mellitus, including coronary artery disease and congestive heart failure, including the preoperative assessment and perioperative management of the surgical patient with diabetes mellitus. Part III, the peripheral vascular system, addresses epidemiology (incidence and prevalence), mechanisms, methods of assessment, and treatment of this macrovascular disease. Specific topics include diabetes and arterial stiffness, methods for assessing large vessel pathophysiology, and peripheral vascular disease in patients with diabetes mellitus. And Part IV reviews the different microvascular effects in individuals with diabetes mellitus, including retinopathy (eye disease), nephropathy (kidney disease), neuropathy (nerve disease), and microcirculation of the diabetic foot. Each chapter includes extensive references and a subject index concludes the text.
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 “atherosclerosis” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “atherosclerosis” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “atherosclerosis” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com):
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A Slide Atlas of Atherosclerosis Progression and Regression on CD-ROM by Herbert C. Stary; ISBN: 184214152X; http://www.amazon.com/exec/obidos/ASIN/184214152X/icongroupinterna
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Advances in Lipoprotein and Atherosclerosis Research, Diagnostics and Treatment: Proceedings of the 8th International Dresden Lipid Symposium Held at Dresden, June 10-12, 1994 by Werner Jaross (Editor), et al; ISBN: 3334609545; http://www.amazon.com/exec/obidos/ASIN/3334609545/icongroupinterna
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An Atlas of Atherosclerosis Progression and Regression by Herbert C. Stary, Starry; ISBN: 1850704805; http://www.amazon.com/exec/obidos/ASIN/1850704805/icongroupinterna
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Arachidonic Acid Metabolites (Atherosclerosis Reviews) by Ruth Johnsson Hegyeli (Editor); ISBN: 0881671312; http://www.amazon.com/exec/obidos/ASIN/0881671312/icongroupinterna
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Arterial Pollution: An Integrated View on Atherosclerosis (NATO Advanced Science Institutes Series. Series A, Life Sciences, V. 58) by NATO Advanced Study Institute on Arterial Pollution: An Integrated Vie, et al; ISBN: 0306412438; http://www.amazon.com/exec/obidos/ASIN/0306412438/icongroupinterna
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Atherosclerosis & Atherectomy: Index of New Information & Medical Research Bible by MacKson (1994); ISBN: 0788301268; http://www.amazon.com/exec/obidos/ASIN/0788301268/icongroupinterna
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Atherosclerosis (Annals of the New York Academy of Sciences, Vol 454) by K.t Lee (Editor); ISBN: 0897663039; http://www.amazon.com/exec/obidos/ASIN/0897663039/icongroupinterna
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Atherosclerosis 5: The Fifth Saratoga International Conference (Annals of the New York Academy of Sciences, Vol 902) by Sp Saratoga International Conference on Atherosclerosis 199 Barcelona, et al (2000); ISBN: 1573312460; http://www.amazon.com/exec/obidos/ASIN/1573312460/icongroupinterna
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Atherosclerosis and Arteriosclerosis by Rodney A. White (Editor), et al; ISBN: 0849363578; http://www.amazon.com/exec/obidos/ASIN/0849363578/icongroupinterna
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Atherosclerosis and Autoimmunity by Yehuda Shoenfeld (Editor), et al; ISBN: 0444506691; http://www.amazon.com/exec/obidos/ASIN/0444506691/icongroupinterna
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Atherosclerosis and Cardiovascular Disease: 7th International Meeting by G.C. Descovich, et al (1991); ISBN: 0792389492; http://www.amazon.com/exec/obidos/ASIN/0792389492/icongroupinterna
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Atherosclerosis and Cardiovascular Diseases: Proceedings of the Sixth International Meeting on Atherosclerosis and Cardiovascular Diseases, Held in by International Meeting on Atherosclerosis and Cardiovascular Diseases (1988); ISBN: 0852008368; http://www.amazon.com/exec/obidos/ASIN/0852008368/icongroupinterna
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Atherosclerosis and Coronary Artery Disease by Valentin Fuster (Editor), et al (1998); ISBN: 0781702666; http://www.amazon.com/exec/obidos/ASIN/0781702666/icongroupinterna
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Atherosclerosis and Heart Disease by Andrew Tonkin, Freek Verheugt; ISBN: 1841841234; http://www.amazon.com/exec/obidos/ASIN/1841841234/icongroupinterna
244 Atherosclerosis
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Atherosclerosis II : recent progress in atherosclerosis research :the Second Saratoga International Conference on Atherosclerosis in Towada; ISBN: 0897666062; http://www.amazon.com/exec/obidos/ASIN/0897666062/icongroupinterna
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Atherosclerosis II: Recent Progress in Atherosclerosis Research: The Second Saratoga International Conference on Atherosclerosis in Towada (Annals) by K.T. Lee, et al (1990); ISBN: 0897666054; http://www.amazon.com/exec/obidos/ASIN/0897666054/icongroupinterna
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Atherosclerosis III: Recent Advances in Atherosclerosis Research: The Third Saratoga International Conference on Atherosclerosis in Nekoma (Annals) by Fujio Numano, Robert W. Wissler (1995); ISBN: 089766812X; http://www.amazon.com/exec/obidos/ASIN/089766812X/icongroupinterna
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Atherosclerosis in Primates by Jack Perry Strong (1976); ISBN: 3805521952; http://www.amazon.com/exec/obidos/ASIN/3805521952/icongroupinterna
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Atherosclerosis IV: Recent Advances in Atherosclerosis Research: The Fourth Saratoga International Conference on Atherosclerosis (Annals of the New York Academy of Sciences, V. 811) by Fujio/ Ross, Russell Saratoga International Conference on Atherosclerosis 1996 Hawaii)/ Numano (1997); ISBN: 1573310239; http://www.amazon.com/exec/obidos/ASIN/1573310239/icongroupinterna
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Atherosclerosis IV: Recent Advances in Atheroslcerosis Research: The Fourth Saratoga International Conference on Atherosclerosis (Annals of the New York Academy of Science, Vol 811) by Fujio/ Ross, Russel Saratoga International Conference on Atherosclerosis 1996 Hawaii)/ Numano (Editor), Fujio Numano (1997); ISBN: 1573310220; http://www.amazon.com/exec/obidos/ASIN/1573310220/icongroupinterna
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Atherosclerosis Prevention: Identification and Treatment of the Child With High Cholesterol (Monographs in Clinical Pediatrics, Vol 4) by Marc S. Jacobson (Editor) (1991); ISBN: 3718651211; http://www.amazon.com/exec/obidos/ASIN/3718651211/icongroupinterna
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Atherosclerosis Reviews by Rodolfo Paoletti (Editor), Antonio M., Jr. Gotto (Editor) (1987); ISBN: 0881671894; http://www.amazon.com/exec/obidos/ASIN/0881671894/icongroupinterna
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Atherosclerosis Reviews: End Points for Cardiovascular Drug Studies by Ruth Johnsson Hegyeli (Editor) (1984); ISBN: 0890049556; http://www.amazon.com/exec/obidos/ASIN/0890049556/icongroupinterna
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Atherosclerosis VI: The Sixth Saratoga International Conference (Annals of the New York Academy of Sciences, V. 947) by Japan)/ Numano, Fujio/ Gimbrone, Michael A. Saratoga International Conference on Atherosclerosis 200 Tokyo, Fujio Numano (2001); ISBN: 1573313653; http://www.amazon.com/exec/obidos/ASIN/1573313653/icongroupinterna
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Atherosclerosis X by F. Peter Woodford (Editor), J. Davignon (Editor); ISBN: 0444820078; http://www.amazon.com/exec/obidos/ASIN/0444820078/icongroupinterna
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Atherosclerosis XII by Sweden)/ Stemme, S./ Stemme, Sten/ Olsson, Anders G. International Symposium on Atherosclerosis 2000 Stockholm, et al; ISBN: 0444505512; http://www.amazon.com/exec/obidos/ASIN/0444505512/icongroupinterna
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245
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Atherosclerosis, Clinical Evaluation and Therapy by S. Lenzi (Editor), G.C. Descovich (Editor) (1983); ISBN: 0852004494; http://www.amazon.com/exec/obidos/ASIN/0852004494/icongroupinterna
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Atherosclerosis: A Pediatric Perspective by M.T.R. Subbiah (Editor) (1989); ISBN: 0849347734; http://www.amazon.com/exec/obidos/ASIN/0849347734/icongroupinterna
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Atherosclerosis: Biology and Clinical Science by G. Anders Olsson (Editor) (1987); ISBN: 044303169X; http://www.amazon.com/exec/obidos/ASIN/044303169X/icongroupinterna
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Atherosclerosis: Cattle As a Model for Study in Man (Monographs on Atherosclerosis, Vol 12) by Ivan N. Likar, et al (1986); ISBN: 3805540698; http://www.amazon.com/exec/obidos/ASIN/3805540698/icongroupinterna
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Atherosclerosis: Cellular and Molecular Interactions in the Artery Wall (Altschul Symposia Series, Vol 1) by Avrum I. Gotlieb, et al (1991); ISBN: 0306439239; http://www.amazon.com/exec/obidos/ASIN/0306439239/icongroupinterna
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Atherosclerosis: Is It Reversible? by G. Schettler (Editor) (1978); ISBN: 0387085823; http://www.amazon.com/exec/obidos/ASIN/0387085823/icongroupinterna
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Atherosclerosis: Metabolism, Risk and Control, Proceedings of the 11th Annual Arnold O. Beckman Conference in Clinical Chemistry (Special Issue of C) by Arnold O Beckman Conference in Clinical, J. Dickson (Editor) (1988); ISBN: 0915274493; http://www.amazon.com/exec/obidos/ASIN/0915274493/icongroupinterna
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Atherosclerosis: Pathology of the Vasculature in Live Patients by Jeffrey M. Isner, Marianne Kearney (1999); ISBN: 0702019275; http://www.amazon.com/exec/obidos/ASIN/0702019275/icongroupinterna
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Atherosclerosis: Risk Factors & Treatment by W. Virgil Brown (Editor), et al; ISBN: 1878132318; http://www.amazon.com/exec/obidos/ASIN/1878132318/icongroupinterna
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Bile Acids and Atherosclerosis (Atherosclerosis Reviews, Vol 15) by Scott M. Grundy (Editor) (1986); ISBN: 0881672432; http://www.amazon.com/exec/obidos/ASIN/0881672432/icongroupinterna
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Biochemistry of Diabetes and Atherosclerosis (Developments in Molecular and Cellular Biochemistry, 42) by James S. C. Gilchrist (Editor), et al (2003); ISBN: 1402074239; http://www.amazon.com/exec/obidos/ASIN/1402074239/icongroupinterna
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Blood Cells and Arteries in Hypertension and Atherosclerosis (Atherosclerosis Reviews, Vol 19) by Philippe Meyer, Pierre Marche (Editor) (1989); ISBN: 0881674753; http://www.amazon.com/exec/obidos/ASIN/0881674753/icongroupinterna
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Blood Flow in Large Arteries: Applications to Atherogenesis and Clinical Medicine (Monographs on Atherosclerosis, Vol 15) by D.W. Liepsch (Editor) (1990); ISBN: 3805549830; http://www.amazon.com/exec/obidos/ASIN/3805549830/icongroupinterna
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Cell Interactions in Atherosclerosis by Horst Robenek, Nicholas John Severs; ISBN: 0849355052; http://www.amazon.com/exec/obidos/ASIN/0849355052/icongroupinterna
246 Atherosclerosis
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Cholesterol and Atherosclerosis: Diagnosis and Treatment by Scott M. Grundy; ISBN: 0397446748; http://www.amazon.com/exec/obidos/ASIN/0397446748/icongroupinterna
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Clinical Diagnosis of Atherosclerosis: Quantitative Methods of Evaluation by M. Gene Bond; ISBN: 0387907807; http://www.amazon.com/exec/obidos/ASIN/0387907807/icongroupinterna
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Cologne Atherosclerosis Conference No 4 Cholesterol-Homeostasis (Agents and Actions Supplements Vol 26) by M.J. Parnham, R. Niemann (Editor) (1988); ISBN: 0817622470; http://www.amazon.com/exec/obidos/ASIN/0817622470/icongroupinterna
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Cologne Atherosclerosis Conference, No. 2, Lipids (Agents and Actions Supplements, Vol 16) by Michael J. Parnham (Editor) (1984); ISBN: 3764316454; http://www.amazon.com/exec/obidos/ASIN/3764316454/icongroupinterna
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Cologne Atherosclerosis Conference: Inflammatory Aspects (Agents and Actions Supplements, V. 11) by Michael J./ Winkelmann, Johannes Cologne Atherosclerosis Conference 1982)/ Winkelmann/ Parnham (1982); ISBN: 3764313250; http://www.amazon.com/exec/obidos/ASIN/3764313250/icongroupinterna
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Diabetes and Atherosclerosis (1993); ISBN: 0444016651; http://www.amazon.com/exec/obidos/ASIN/0444016651/icongroupinterna
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Diabetes and Atherosclerosis (Developments in Cardiovascular Medicine, 125) by Robert W. Stout (Editor) (1992); ISBN: 0792313100; http://www.amazon.com/exec/obidos/ASIN/0792313100/icongroupinterna
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Diabetes and Atherosclerosis: Molecular Basis and Clinical Aspects by Boris, M.D., Ph.D. Draznin, Robert H., Ph.D. Eckel (Editor) (1993); ISBN: 0412044315; http://www.amazon.com/exec/obidos/ASIN/0412044315/icongroupinterna
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Diet and atherosclerosis : [proceedings of the International Course on Diet and Atherosclerosis, held in Rome, Italy, November 1-3, 1973]; ISBN: 0306390604; http://www.amazon.com/exec/obidos/ASIN/0306390604/icongroupinterna
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Diet and Drugs in Atherosclerosis: European Atherosclerosis Group Meeting, Lugano, Switzerland by Noseda; ISBN: 0890044910; http://www.amazon.com/exec/obidos/ASIN/0890044910/icongroupinterna
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Dietary Proteins and Atherosclerosis by Gerard Debry (2003); ISBN: 0849321026; http://www.amazon.com/exec/obidos/ASIN/0849321026/icongroupinterna
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Dietary Proteins, Cholesterol Metabolism and Atherosclerosis (Monographs on Atherosclerosis, Vol 16) by A.C. Beynen (Editor), Michihiro Sugano (1990); ISBN: 3805551932; http://www.amazon.com/exec/obidos/ASIN/3805551932/icongroupinterna
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Drugs, lipid metabolism, and atherosclerosis : [proceedings]; ISBN: 0306400529; http://www.amazon.com/exec/obidos/ASIN/0306400529/icongroupinterna
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Eicosanoids, Apolipoproteins, Lipoprotein Particles, and Atherosclerosis (Advances in Experimental Medicine and Biology, 243) by Claude L. Malmendier, Petar Alaupovic (Editor) (1989); ISBN: 0306430371; http://www.amazon.com/exec/obidos/ASIN/0306430371/icongroupinterna
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Emotions, Hormones & Atherosclerosis by E. I. Sokolov (1994); ISBN: 9067641677; http://www.amazon.com/exec/obidos/ASIN/9067641677/icongroupinterna
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247
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Endemic Diseases and Risk Factors for Atherosclerosis in the Far East (1988); ISBN: 3540188479; http://www.amazon.com/exec/obidos/ASIN/3540188479/icongroupinterna
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Endothelium, Nitric Oxide, and Atherosclerosis: From Basic Mechanisms to Clinical Implications by Julio A., Md. Panza (Editor), Richard O. Cannon (Editor); ISBN: 0879934360; http://www.amazon.com/exec/obidos/ASIN/0879934360/icongroupinterna
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Enzyme biochemistry of the arterial wall as related to atherosclerosis by Tibor Zemplényi; ISBN: 0853240485; http://www.amazon.com/exec/obidos/ASIN/0853240485/icongroupinterna
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Expanding Horizons in Atherosclerosis Research: To Gotthard Schettler on His Seventieth Birthday by G. Schlierf (Editor) (1987); ISBN: 038717365X; http://www.amazon.com/exec/obidos/ASIN/038717365X/icongroupinterna
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Extracoronary Atherosclerosis (Monographs on Atherosclerosis, Vol 14) by A. Ventura (Editor), et al (1986); ISBN: 3805541627; http://www.amazon.com/exec/obidos/ASIN/3805541627/icongroupinterna
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Fluid Dynamics As a Localizing Factor for Atherosclerosis by G. Schettler (Editor); ISBN: 0387123938; http://www.amazon.com/exec/obidos/ASIN/0387123938/icongroupinterna
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Genetic Factors in Atherosclerosis: Approaches and Model Systems (Monographs in Human Genetics, Vol 12) by R.S. Sparkes, A.J. Lusis (Editor) (1989); ISBN: 3805548907; http://www.amazon.com/exec/obidos/ASIN/3805548907/icongroupinterna
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Hdl Deficiency and Atherosclerosis (Developments in Cardiovascular Medicine, 174) by G. Assmann (Editor) (1996); ISBN: 0792388887; http://www.amazon.com/exec/obidos/ASIN/0792388887/icongroupinterna
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Hemodynamic Basic of Atherosclerosis by texon M; ISBN: 0891161465; http://www.amazon.com/exec/obidos/ASIN/0891161465/icongroupinterna
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Hemodynamic Basis of Atherosclerosis: With Critique of the Cholesterol-Heart Disease Hypothesis by Meyer Texon (1996); ISBN: 1567000290; http://www.amazon.com/exec/obidos/ASIN/1567000290/icongroupinterna
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High-Density Lipoproteins: Physiopathological Aspects and Clinical Significance (Atherosclerosis Reviews, Vol 16) by Alberico L. Catapano, et al (1987); ISBN: 0881672904; http://www.amazon.com/exec/obidos/ASIN/0881672904/icongroupinterna
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Human Apolipoprotein Mutants: Impact on Atherosclerosis and Longevity (NATO Asi Series A, Life Sciences, Vol 112) by NATO Advanced Research Workshop on Human Apolipoprotein Mutants--Impac, et al; ISBN: 0306423707; http://www.amazon.com/exec/obidos/ASIN/0306423707/icongroupinterna
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Human Atherosclerosis (Soviet Medical Reviews Series, Section A) by E.I. Chazov; ISBN: 3718603497; http://www.amazon.com/exec/obidos/ASIN/3718603497/icongroupinterna
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Hypercholesterolemia & Atherosclerosis: Pathogenesis & Prevention by Jerrold M. Olefsky (Editor), Daniel Steinberg (Editor) (1987); ISBN: 0783778732; http://www.amazon.com/exec/obidos/ASIN/0783778732/icongroupinterna
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Hypercholesterolemia and Atherosclerosis: Pathogenesis and Prevention (Contemporary Issues in Endocrinology and Metabolism, Vol 3) by Daniel Steinberg,
248 Atherosclerosis
Jerrold M. Olefsky (Editor); ISBN: 044308453X; http://www.amazon.com/exec/obidos/ASIN/044308453X/icongroupinterna •
Hypercholesterolemia: Clinical and Therapeutic Implications (Atherosclerosis Reviews, Vol 18) by Joseph Stokes, Mario Mancini (Editor) (1988); ISBN: 0881674354; http://www.amazon.com/exec/obidos/ASIN/0881674354/icongroupinterna
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Hyperlipidemia in Childhood and the Development of Atherosclerosis (Annals of the New York Academy of Sciences, V. 623) by Christine L. Williams, Ernst L. Wynder (Editor) (1991); ISBN: 0897666577; http://www.amazon.com/exec/obidos/ASIN/0897666577/icongroupinterna
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Inflammatory and Infectious Basis of Atherosclerosis (Pir-Progress in Inflammation Research) by Jay L. Mehta (Editor) (2001); ISBN: 3764361549; http://www.amazon.com/exec/obidos/ASIN/3764361549/icongroupinterna
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Inflammatory Atherosclerosis: Characteristics of the Injurious Agent by Heart Research Foundation, Richard J. Frink (2002); ISBN: 0972481605; http://www.amazon.com/exec/obidos/ASIN/0972481605/icongroupinterna
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Latent Dyslipoproteinemias and Atherosclerosis by J.L. De Gennes, et al; ISBN: 089004306X; http://www.amazon.com/exec/obidos/ASIN/089004306X/icongroupinterna
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Lipid-Lowering Therapy and Progression of Coronary Atherosclerosis (Developments in Cardiovascular Medicine, 180) by A. V. G. Bruschke (Editor), et al (1996); ISBN: 0792338073; http://www.amazon.com/exec/obidos/ASIN/0792338073/icongroupinterna
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Lipids and Atherosclerosis Annual by Gaw, et al; ISBN: 1853179043; http://www.amazon.com/exec/obidos/ASIN/1853179043/icongroupinterna
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Lipids and Atherosclerosis Annual 2003 by Allan Gaw (Editor), James Shepherd (2003); ISBN: 1841842990; http://www.amazon.com/exec/obidos/ASIN/1841842990/icongroupinterna
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Lipoproteins and Atherosclerosis (Advances in Experimental Medicine and Biology, 210) by C.L. Malmendier, P. Alaupovic (Editor); ISBN: 0306424878; http://www.amazon.com/exec/obidos/ASIN/0306424878/icongroupinterna
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Lipoproteins and Coronary Atherosclerosis: Proceedings of the International Symposium on Lipoproteins and Coronary Atherosclerosis Held in Lugano, Switzerland, October 1-3, 1981 by International Symposium on Lipoproteins and Coronary Atherosclerosis (1982); ISBN: 0444804080; http://www.amazon.com/exec/obidos/ASIN/0444804080/icongroupinterna
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Medical Management of Atherosclerosis (Clinical Guides to Medical Management) by John C. Larosa (Editor) (1998); ISBN: 0824701496; http://www.amazon.com/exec/obidos/ASIN/0824701496/icongroupinterna
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Modified Lipoproteins in the Pathogenesis of Atherosclerosis (Medical Intelligence Unit) by Sampath, Ph.D. Parthasarathy (1994); ISBN: 157059080X; http://www.amazon.com/exec/obidos/ASIN/157059080X/icongroupinterna
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Molecular Genetics of Coronary Artery Disease: Candidate Genes and Processes in Atherosclerosis (Monographs in Human Genetics, Vol. 14) by Aldons J. Lusis, et al (1992); ISBN: 380555558X; http://www.amazon.com/exec/obidos/ASIN/380555558X/icongroupinterna
Books
249
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Natural Antioxidants and Food Quality in Atherosclerosis and Cancer Prevention (Rsc Special Publications, 181) by J, T. Kumpulainen, J. T. Salonen (1996); ISBN: 0854047212; http://www.amazon.com/exec/obidos/ASIN/0854047212/icongroupinterna
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Natural History of Coronary Atherosclerosis by Constantin,M.D.,Ph.D. Velican, Doina, M.D. Velican (1989); ISBN: 0849369355; http://www.amazon.com/exec/obidos/ASIN/0849369355/icongroupinterna
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Non-Invasive Imaging of Atherosclerosis (Developments in Cardiovascular Medicine, 199) by Michele, MD Mercuri (Editor), et al (1998); ISBN: 0792380363; http://www.amazon.com/exec/obidos/ASIN/0792380363/icongroupinterna
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Noninvasive Techniques for Assessment of Atherosclerosis in Peripheral, Carotid and Coronary Arteries by Thomas F. Budinger (1982); ISBN: 0890046794; http://www.amazon.com/exec/obidos/ASIN/0890046794/icongroupinterna
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Pathology of Atherosclerosis by Neville Woolf, T. Crawford (Editor) (1982); ISBN: 0407001255; http://www.amazon.com/exec/obidos/ASIN/0407001255/icongroupinterna
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Platelets and Atherosclerosis (1991); ISBN: 3540530061; http://www.amazon.com/exec/obidos/ASIN/3540530061/icongroupinterna
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Recent Progress in Atherosclerosis Research (1993); ISBN: 3540543945; http://www.amazon.com/exec/obidos/ASIN/3540543945/icongroupinterna
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Recent Progress in Atherosclerosis Research (Current Topics in Pathology, Vol 87) by E. Vollmer, A. Roessner (Editor) (1994); ISBN: 0387543945; http://www.amazon.com/exec/obidos/ASIN/0387543945/icongroupinterna
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Reversing Atherosclerosis by Geoffrey Austin Gresham; ISBN: 0398039313; http://www.amazon.com/exec/obidos/ASIN/0398039313/icongroupinterna
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Syndromes of Atherosclerosis: Correlations of Clinical Imaging and Pathology by Valentin Fuster (Editor), et al; ISBN: 087993638X; http://www.amazon.com/exec/obidos/ASIN/087993638X/icongroupinterna
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The Nutritional Bypass : Reverse Atherosclerosis Without Surgery by David W. Rowland; ISBN: 189665102X; http://www.amazon.com/exec/obidos/ASIN/189665102X/icongroupinterna
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The Pathogenesis of atherosclerosis; ISBN: 0683091956; http://www.amazon.com/exec/obidos/ASIN/0683091956/icongroupinterna
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The Role of Aging in Atherosclerosis: The Sequestration Hypothesis by Richard E., Md., Ph.D. Tracy (2003); ISBN: 1402012233; http://www.amazon.com/exec/obidos/ASIN/1402012233/icongroupinterna
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The Role of Cholesterol in Atherosclerosis: New Therapeutic Opportunities by Scott M. Grundy, Alexander G. Bearn (Editor) (1988); ISBN: 0932883133; http://www.amazon.com/exec/obidos/ASIN/0932883133/icongroupinterna
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Tobacco Smoking and Atherosclerosis: Pathogenesis and Cellular Mechanisms (Advances in Experimental Medicine and Biology, 273) by John N. Diana (Editor); ISBN: 030643668X; http://www.amazon.com/exec/obidos/ASIN/030643668X/icongroupinterna
250 Atherosclerosis
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Unclog Your Arteries : How I Beat Atherosclerosis by Gene McDougall (2001); ISBN: 0759622795; http://www.amazon.com/exec/obidos/ASIN/0759622795/icongroupinterna
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Unsaturated fatty acids in atherosclerosis by Jean Enselme; ISBN: 0080130607; http://www.amazon.com/exec/obidos/ASIN/0080130607/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “atherosclerosis” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
A Controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis, by Semour Dayton [et al.]. Author: Dayton, Seymour,; Year: 1970; New York, American Heart Assn., 1969
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A current technique of aortoiliac and femoropopliteal endarterectomy for obliterative atherosclerosis. Author: Cannon, Jack Arlo,; Year: 1965; Springfield, Ill., Thomas [c1965]
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A study of the amino acid composition of some of the serum lipoproteins involved in the development of atherosclerosis. Author: Karler, Arthur.; Year: 1970; Berkeley [1952]
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Atherosclerosis and body-build, with special reference to size and number of subcutaneous fat cells. [Tr. by L. James Brown]. Author: Bjurulf, Per.; Year: 1959; Lund, Berlingska Boktryckeriet, 1959
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Atherosclerosis and thrombosis. Edited by A. Myasnikov. Author: Institut terapii (Akademiia meditsinskikh nauk SSSR); Year: 1968; Moscow, MIR Publishers, 1967
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Atherosclerosis; pathology, physiology, aetiology, diagnosis, and clinical management, edited by F. G. Schettler and G. S. Boyd. Author: Schettler, Gotthard.; Year: 1961; Amsterdam, New York, Elsevier, 1969; ISBN: 444406921
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Cholesterol, bile acids and atherosclerosis; a biochemical review. Author: Belle, Herman van.; Year: 1965; Amsterdam, North-Holland Pub. Co., 1965
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Comparative atherosclerosis; the morphology of spontaneous and induced atherosclerotic lesions in animals and its relation to human disease, by 56 authors. Ed. by James C. Roberts, Jr. and Reuben Straus, with Miriam S. Cooper, editorial associate. Author: Roberts, James Christy,; Year: 1965; New York, Harper; Row [c1965]
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Diet, lipid metabolism, and atherosclerosis; a review of research grants supported by the National Heart Institute, 1958 to 1964, by May Sherman, with the technical assistance of Nancy J. Hillman. Author: National Heart Institute (U.S.); Year: 1962; Bethesda, Md., Extramural Programs, National Heart Institute [1965]
11
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
Books
251
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Effect of ileal bypass on aortic atherosclerosis of white Carneau pigeon. Author: Gomes, Manuel Machado Rodrigues,; Year: 1968; [Minneapolis] 1970
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Enzyme biochemistry of the arterial wall as related to atherosclerosis. Author: Zemplényi, Tibor.; Year: 1969; London, Lloyd-Luke, 1968
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Experimental atherosclerosis. Author: Constantinides, Paris,; Year: 1965; Amsterdam, New York, Elsevier, 1965
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Free radicals, lipoprotein oxidation and atherosclerosis: biological and clinical aspects Author: Bellomo, Giorgio.; Year: 2003; London: Richelieu Press, c1995; ISBN: 0903840103
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Hypercholesterolemia and clinical atherosclerosis; a study based on literature and clinical observations. Author: Reisel, Jacob H.; Year: 1968; Rotterdam, Wyt, c1968]
•
Lipid metabolism, obesity, and diabetes mellitus: impact upon atherosclerosis. International symposium, April 1972. [Editors and guest-editors: H. Greten, et al.] Contributors: W. H. Admirand [et al.]. Author: Admirand, W. H.; Year: 1962; Stuttgart, Thieme, 1974; ISBN: 3135076016 http://www.amazon.com/exec/obidos/ASIN/3135076016/icongroupinterna
•
Lipoproteins and ultracentrifugal technique; a symposium. A discussion of techniques used in the Cooperative Study on Lipoproteins and Atherosclerosis. Author: National Advisory Heart Council. Committee on Lipoproteins and Atherosclerosis.; Year: 1967; [Washington?] 1952
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Metabolism of lipids as related to atherosclerosis; a symposium. Author: Kummerow, Fred A. (Fred August),; Year: 1965; Springfield, Ill., Thomas [c1965]
•
Platelet survival studies in man; with special reference to thrombosis and atherosclerosis. Author: Abrahamsen, Arne Foss.; Year: 1968; Copenhagen, Munksgaard, 1968
•
Platelets and the vessel wall-fibrin deposition; symposium of the European Atherosclerosis Group, June 15-17, 1969. Edited by Gotthard Schettler. Author: European Atherosclerosis Group.; Year: 1957; Stuttgart, Thieme, 1970
•
Production of hypercholesterolemia and atherosclerosis in rabbits by feeding different fats without supplementary cholesterol. [Tr. by L. James Brown]. Author: Wigand, Gerhard.; Year: 1965; Lund, Berling, 1959
•
Recent advances in the atherosclerosis; epidemiology, intact organisms, lipoproteins, plasma lipids, whole artery, tissue cultures, hormones, primates, non-primates, platelets, clinical. Edited by C. J. Miras, A. N. Howard [and] R. Paoletti. Author: Howard, Alan N.; Year: 2003; Basel, New York, Karger, 1968
•
Seminar on atherosclerosis and ischaemic heart disease, 19-21 December 1921. Author: Indian Council of Medical Research.; Year: 1965; New Delhi, 1962
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Symposium on atherosclerosis. Mark D. Altschule, guest editor. Author: Altschule, Mark D.; Year: 1972; Philadelphia, Saunders, 1974
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The Geographic pathology of atherosclerosis, edited by Henry C. McGill, Jr. Author: McGill, Henry C.,; Year: 1969; Baltimore, Williams and Wilkins [c1968]
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The mast-cell system: its relationship to atherosclerosis, fibrosis and eosinophils. Author: Fernex, Michel.; Year: 1968; Baltimore, Williams; Wilkins [c1968]
•
The reticuloendothelial system and atherosclerosis; proceedings. Edited by N. R. Di Luzio and Rodolfo Paoletti. Author: Di Luzio, N. R.; Year: 1967; New York, Plenum Press, 1967
•
Unsaturated fatty acids in atherosclerosis. Tr. by R. Crawford. Author: Enselme, J. (Jean),; Year: 1952; New York, Pergamon Press, 1962
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Chapters on Atherosclerosis In order to find chapters that specifically relate to atherosclerosis, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and atherosclerosis 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 “atherosclerosis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on atherosclerosis: •
Diabetes and Atherosclerosis Source: in Johnstone, M.T. and Veves, A. Diabetes and Cardiovascular Disease. Totowa, NJ: The Humana Press, Inc. 2001. p. 169-194. Contact: Humana Press, Inc. 999 Riverview Dr., Suite 208 Totowa, NJ 07512. (973) 2561699. Fax (973) 256-8341. E-mail:
[email protected] PRICE: $125.00, plus shipping and handling. ISBN: 089603755X. Summary: With over ten million diagnosed patients and another five million undiagnosed, diabetes mellitus and its complications is a major public health problem that will assume epidemic proportions as the population grows older. This chapter on diabetes and atherosclerosis (hardening and narrowing of the arteries) is from a textbook that offers physicians practical knowledge about cardiovascular disease and diabetes. This chapter is in Part I, which focuses on pathophysiology, including the mechanisms and risk factors for diabetic cardiovascular disease. The author notes that macrovascular (large vessel) disease is the leading cause of mortality (death) and morbidity (illness) in diabetes. The author discusses endothelial (the cells that line the body cavity and the cardiovascular system) dysfunction, the mechanisms of foam cell formation, the role of humoral immunity and macrophage activation, abnormalities in platelet function, coagulation, and fibrinolysis, particularly as they contribute to thrombus (clot) formation. The author provides updated information concerning factors associated with diabetes that may accelerate the development of atherosclerosis and thrombosis and contribute to acute clinical events. 1 figure. 227 references.
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CHAPTER 8. MULTIMEDIA ON ATHEROSCLEROSIS Overview In this chapter, we show you how to keep current on multimedia sources of information on atherosclerosis. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on atherosclerosis is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “atherosclerosis” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “atherosclerosis” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on atherosclerosis: •
Impotence and Diabetes Source: Los Angeles, CA: National Health Video, Inc. 1999. (videocassette). Contact: Available from National Health Video, Inc. 12021 Wilshire Blvd., Suite 550, Los Angeles, CA 90025. (800) 543-6803. Fax (310) 477-8198. E-mail:
[email protected]. PRICE: $89.00 plus shipping and handling. Summary: This patient education videotape program reviews the problem of erectile dysfunction (impotence) and diabetes mellitus. The program defines erectile dysfunction (ED) as the consistent inability to get and maintain an erection. The program first explores the physiology of erections (how they happen), including the need for mental and physical stimulation, nerve impulses in the brain, and responses in muscles, fibrous tissues, and veins and arteries. The program offers a diagram and the use of a balloon to describe how an erection happens, the anatomy of the corpera cavernosa, and the role of nitrous oxide as a neurochemical transmitter. Age is noted as a factor in ED, and men with diabetes tend to develop ED 10 to 15 years earlier than
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men who do not have diabetes. The program notes that psychological factors (stress, depression, guilt, and performance anxiety) can cause 10 to 15 percent of ED; a series of self test questions are included for viewers to determine if psychological factors may play a role in their own ED. For men with diabetes, nerve damage (peripheral neuropathy) is the most likely culprit for causing ED; damage to the blood vessels (atherosclerosis) is another cause. Poor blood glucose control is the most important factor in both of these problems. The program includes a section noting the impact of drugs (including alcohol and nicotine) on ED. The program outlines the steps in diagnosing erectile problems, including first admitting that there is a problem, talking with a doctor, undergoing diagnostic tests, and participating in treatment. The final section reviews treatment options, reiterating the importance of good blood glucose control and describing the use of drug therapy (Viagra), vacuum erectile systems, self injection, and surgery (blood vessel repair and penile implants). The program includes drawings, graphics, and footage of patients and their physicians through the diagnosis and treatment processes. •
Diabetes: From Detection to Treatment Source: Calhoun, KY: NIMCO. 1994. (videocassette). Contact: Available from NIMCO. P.O. Box 9, 117 Highway 815, Calhoun, KY 423270009. (800) 962-6662 or (502) 273-5050. Fax (502) 273-5844. PRICE: $89.95. Order number: NIM-SM-CD1-V. Summary: This video takes the viewer through the medical detection of diabetes. The model it presents of the cause of diabetes hypothesizes that an environmental trigger in a genetically susceptible person causes inflammation that eventually destroys the cells of the pancreas and leads to a reduction in insulin. The video highlights diabetes symptoms, including polyuria, polydipsia, polyphagia, weight loss, and blurred vision. It explains why people with diabetes consume so much fluid and why they have increased urination. Among the other topics covered are diabetes education, medications and their side effects, diabetic retinopathy, cardiovascular disease, atherosclerosis, foot problems and neuropathy, and renal failure. The video includes numerous comments from physicians and patients.
•
Diabetes and Heart Disease Source: Dallas, TX: American Heart Association. 1996. (videorecording). Contact: Available from Channing L. Bete Company/American Heart Association. Fulfillment Center, 200 State Road, South Deerfield, MA 01373-0200. (800) 611-6083. Fax (800) 499-6464. E-mail:
[email protected]. PRICE: $39.00 plus shipping and handling. Summary: This video, which was developed by the American Heart Association, is intended to help people with diabetes become better informed about heart disease. The video points out that people who have diabetes have a increased risk of developing problems that involve the cardiovascular system. These problems include atherosclerosis (the build up of fatty acids in arteries) and hypertension (high blood pressure). High levels of glucose can damage arteries and increase the likelihood of hypertension and atherosclerosis. In some cases, hypertension may be controlled with changes in lifestyle, such as losing weight, reducing salt intake, and exercising. When lifestyle changes are insufficient to control hypertension, medication is used. The video notes that people must not treat hypertension with over the counter medicines or prescriptions from a friend because they may worsen diabetes or its related conditions.
Multimedia 255
Many of the things that help to manage diabetes can also be effective in reducing the risk of heart disease. Self monitoring of blood glucose, eating healthfully, exercising, taking medication as needed, and educating oneself are each important. The video concludes that people with diabetes can successfully control blood glucose levels and significantly lower the risk of heart disease by making appropriate lifestyle changes and working with health care professionals. An accompanying brochure focuses on topics addressed in the video. The video is available in English or Spanish. (AA-M).
Bibliography: Multimedia on Atherosclerosis The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in atherosclerosis (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on atherosclerosis: •
Atherosclerosis [electronic resource]: risk factors and treatment Source: volume editor, W. Virgil Brown; Year: 1996; Format: Electronic resource; [Philadelphia]: Current Medicine, c1996
•
Atherosclerosis [slide] Source: William B. Strong, Max Miller; Year: 1978; Format: Slide; [Washington: National Audiovisual Center], 1978
•
Atherosclerosis [slide] Source: William B. Strong, Max D. Miller; Year: 1977; Format: Slide; Chapel Hill, N. C.: Health Sciences Consortium, c1977
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Atherosclerosis [slide] Source: Miles Pharmaceuticals; Year: 1986; Format: Slide; [S.l.]: Gardner-Caldwell Synermed, c1986
•
Atherosclerosis and coronary artery disease [slide] Source: Educational Resources Group, University of Missouri-Columbia, Medical Center; Year: 1970; Format: Slide; Columbia, Mo.: The Group, 1970
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Atherosclerosis and coronary heart disease [slide] Source: Association of Pathology Chairmen and National Medical Audiovisual Center; Year: 1975; Format: Slide; Atlanta: The Center, 1975
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Atherosclerosis beyond cholesterol [electronic resource] Source: Sandoz Pharmaceuticals; Year: 1992; Format: Electronic resource; East Hanover, N.J.: Sandoz: Ehrlich Associates, c1992
•
Atherosclerosis-- new frontiers in understanding [videorecording] Source: sponsored as an educational service by Allen & Hanburys; a Health Science Media production; Year: 1991; Format: Videorecording; Research Triangle Park, NC: Glaxo, c1991
•
Basic pathology of atherosclerosis [slide] Source: Bruce A. Warren; Year: 1983; Format: Slide; [Garden Grove, Calif.]: Medcom, c1983
•
Clinical recognition of coronary atherosclerosis [videorecording] Source: Emory University School of Medicine; Year: 1977; Format: Videorecording; Atlanta: Georgia Regional Medical Television Network: [for loan or sale by A. W. Calhoun Medical Library, 1977]
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Co-morbidity and peripheral atherosclerosis [videorecording] Source: Department of Medicine, Emory University, School of Medicine; Year: 1979; Format: Videorecording;
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Atlanta: Emory Medical Television Network: [for loan or sale by A. W. Calhoun Medical Library], 1979 •
Diet and the prevention of atherosclerosis and hypertension [sound recording] Source: American Academy of Pediatrics; Year: 1989; Format: Sound recording; Chicago, IL: Teach'em, [1989]
•
High density lipoprotein [videorecording]: its physiology, pathology, and relationship to artherosclerosis [i.e. atherosclerosis] Source: Dallas Area Hospital Television System; Year: 1979; Format: Videorecording; [Dallas, Tex.]: The System, c1979
•
Lipid transport and atherosclerosis [videorecording] Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1980; Format: Videorecording; Atlanta: Emory Medical Television Network, 1980
•
Panoramic view of problems associated with coronary atherosclerosis [videorecording] Source: Georgia Regional Medical Television Network; Year: 1972; Format: Videorecording; [Atlanta: The Network: [for loan and sale by A. W. Calhoun Medical Library, 1972]
•
Potential for regression of atherosclerosis in animals [videorecording] Source: Marshfield Medical Foundation in cooperation with Marshfield Clinic & St. Joseph's Hospital; Year: 1983; Format: Videorecording; Marshfield, WI: Marshfield Regional Video Network, 1983
•
Primary prevention of atherosclerosis in childhood [videorecording]: the role of lipids. Year: 1985; Format: Videorecording; [United States: s.n., 1985]
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Progression and regression of coronary atherosclerosis [videorecording]: lessons from the UW fats trial Source: produced in the facilities of Instructional Media Services, University of Washington; Year: 1990; Format: Videorecording; [Seattle, Wash.]: The University, c1990
•
Redox state and the pathogenesis of atherosclerosis [videorecording]: relationship to the coronary ischemic syndromes Source: [presented by] the Emory Medical Television Network, Emory University School of Medicine of the Robert W. Woodruff Health Sciences Cen; Year: 1994; Format: Videorecording; Atlanta, GA: The University, c1994
•
Regression of atherosclerosis [videorecording] Source: Marshfield Clinic, Saint Joseph's Hospital; a presentation of the Marshfield Video Network; Year: 1994; Format: Videorecording; Marshfield, WI: The Clinic, [1994]
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Surgical treatment of coronary atherosclerosis [motion picture] Source: produced in collaboration with Medical Department, Ives Laboratories Inc; Year: 1971; Format: Motion picture; [United States: Ives Laboratories, 1971]
•
The Etiology of atherosclerosis [videorecording] Source: Emory University School of Medicine; Year: 1977; Format: Videorecording; Atlanta: Georgia Regional Medical Television Network: [for loan or sale by A. W. Calhoun Medical Library, 1977]
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CHAPTER 9. PERIODICALS ATHEROSCLEROSIS
AND
NEWS
ON
Overview In this chapter, we suggest a number of news sources and present various periodicals that cover atherosclerosis.
News Services and Press Releases One of the simplest ways of tracking press releases on atherosclerosis 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 “atherosclerosis” (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 atherosclerosis. 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 “atherosclerosis” (or synonyms). The following was recently listed in this archive for atherosclerosis: •
Endogenous ozone may underlie progression of atherosclerosis Source: Reuters Medical News Date: November 06, 2003
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•
Apolipoprotein variant cuts atherosclerosis in heart disease patients Source: Reuters Industry Breifing Date: November 04, 2003
•
Subclinical atherosclerosis precedes clinical onset of diabetes Source: Reuters Medical News Date: October 20, 2003
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C. pneumoniae's platelet activation could be link to atherosclerosis Source: Reuters Medical News Date: September 22, 2003
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Nuclear receptor could represent new target for anti-atherosclerosis drugs Source: Reuters Industry Breifing Date: September 12, 2003
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Aggressive lipid lowering does not slow atherosclerosis Source: Reuters Health eLine Date: August 04, 2003
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Physical activity may slow atherosclerosis Source: Reuters Health eLine Date: August 01, 2003
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Degree of leisure time physical activity inversely correlates with atherosclerosis Source: Reuters Medical News Date: August 01, 2003
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Tooth loss associated with subclinical atherosclerosis Source: Reuters Medical News Date: July 31, 2003
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Adolescent blood pressure predicts atherosclerosis in adulthood Source: Reuters Medical News Date: July 29, 2003
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Subclinical atherosclerosis associated with parental coronary heart disease Source: Reuters Medical News Date: July 21, 2003
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Age-related stem cell loss prevents artery repair and contributes to atherosclerosis Source: Reuters Medical News Date: July 16, 2003
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Serum testosterone inversely associated with atherosclerosis in diabetic men Source: Reuters Medical News Date: July 02, 2003
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HDL mimetic reduces atherosclerosis in phase II study Source: Reuters Medical News Date: June 26, 2003
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Esperion atherosclerosis drug appears effective in phase II study Source: Reuters Industry Breifing Date: June 26, 2003
•
Polycystic ovary syndrome increases risk of coronary atherosclerosis Source: Reuters Medical News Date: June 06, 2003
Periodicals and News
•
Chlamydia pneumoniae recruits monocytes to atherosclerosis-susceptible vessel walls Source: Reuters Medical News Date: May 26, 2003
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Soluble Fas levels predict atherosclerosis in dialysis patients Source: Reuters Medical News Date: May 16, 2003
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Pneumococcal vaccine modulates atherosclerosis in mice Source: Reuters Medical News Date: May 16, 2003
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Alpha-1-antitrypsin gene variants associated with atherosclerosis progression Source: Reuters Medical News Date: April 24, 2003
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LRP1 "pivotal" in preventing atherosclerosis in mice Source: Reuters Medical News Date: April 10, 2003
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Atherosclerosis associated with venous thrombosis Source: Reuters Medical News Date: April 09, 2003
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Serum levels of soluble CD40 ligand may indicate high-risk atherosclerosis Source: Reuters Medical News Date: March 19, 2003
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Fat location more important than amount in predicting atherosclerosis risk Source: Reuters Medical News Date: March 17, 2003
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Hepatitis C associated with atherosclerosis in patients with diabetes Source: Reuters Medical News Date: March 12, 2003
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Serum levels of metalloproteinase PAPP-A tied to atherosclerosis risk in men Source: Reuters Medical News Date: February 19, 2003
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Factor VII synthesized by cells involved in atherosclerosis Source: Reuters Medical News Date: February 14, 2003
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HIV protease inhibitors promote atherosclerosis independent of dyslipidemia Source: Reuters Medical News Date: January 22, 2003
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Sildenafil can stimulate platelet aggregation if atherosclerosis is present Source: Reuters Industry Breifing Date: January 16, 2003
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Endogenous hormones may be protective against atherosclerosis in elderly men Source: Reuters Medical News Date: January 14, 2003
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AtheroGenics set to begin phase III trial of lead atherosclerosis drug Source: Reuters Industry Breifing Date: January 14, 2003
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•
Serum albumin not linked to carotid atherosclerosis Source: Reuters Medical News Date: January 10, 2003
•
Activated platelets promote atherosclerosis Source: Reuters Medical News Date: December 26, 2002
•
Atherosclerosis risk factors do not predict progressive kidney disease Source: Reuters Medical News Date: December 25, 2002
•
C pneumoniae may be linked to carotid artery atherosclerosis Source: Reuters Medical News Date: December 24, 2002
•
C-reactive protein predicts subclinical carotid atherosclerosis in women Source: Reuters Medical News Date: November 01, 2002 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 “atherosclerosis” (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
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you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “atherosclerosis” (or synonyms). If you know the name of a company that is relevant to atherosclerosis, 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 “atherosclerosis” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “atherosclerosis” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on atherosclerosis: •
Atherosclerosis and Coronary Artery Disease in SLE Source: Lupus News. 20(2): 6-7. Spring 2000. Contact: Available from Lupus Foundation of America. 1300 Piccard Drive, Suite 200, Rockville, MD 20850-4303. (800) 558-0121 or (301) 670-9292. Fax (301) 670-9486. Website: www.lupus.org/lupus. Summary: This newsletter article provides health professionals and people who have systemic lupus erythematosus (SLE) with information on atherosclerosis and coronary artery disease in SLE. Accelerated atherosclerosis has become recognized as one of the causes of illness and death in people with SLE. The prevalence of coronary artery disease in lupus varies, and deaths from atherosclerosis tend to occur in older people who have had lupus for longer periods of time. Although mortality rates from atherosclerosis appear low, people who have lupus and atherosclerosis are usually younger than the typical person with atherosclerosis. Routine tests such as stress testing and electrocardiograms used to detect early coronary artery disease may be unreliable in people who have lupus, and some people may not be able to undergo the exercise necessary to complete the tests properly. Known risk factors for coronary disease in the general population, including hypertension, diabetes, and lipid disorders, may be magnified in people who have lupus. These factors, and older age and postmenopausal status, are linked with coronary artery disease in people who have lupus. SLE itself also appears to be a risk factor for coronary disease. Awareness of the issue of lupus related coronary artery disease by both the physician and patient is important.
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Academic Periodicals covering Atherosclerosis Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to atherosclerosis. In addition to these sources, you can search for articles covering atherosclerosis that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for atherosclerosis. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with atherosclerosis. 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 atherosclerosis: Ascorbic Acid (Vitamin C) •
Systemic - U.S. Brands: Ascorbicap; Cecon; Cee-500; Cemill; Cenolate; Cetane; Cevi-Bid; Flavorcee; Ortho/CS; Sunkist http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202071.html
Cholestyramine •
Oral - U.S. Brands: Questran http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202137.html
Clopidogrel •
Systemic - U.S. Brands: Plavix http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203403.html
Colestipol •
Oral - U.S. Brands: Colestid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202161.html
Estrogens •
Systemic - U.S. Brands: Alora; Aquest; Climara; Clinagen LA 40; Delestrogen; depGynogen; Depo-Estradiol; Depogen; Dioval 40; Dioval XX; Dura-Estrin; Duragen-20; E-Cypionate; Estinyl; Estrace; Estraderm; Estragyn 5; Estragyn LA 5; Estra-L 40; Estratab; Estro-A; Estro-Cyp; Estro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202226.html
Gemfibrozil •
Systemic - U.S. Brands: Lopid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202256.html
Probucol •
Systemic - U.S. Brands: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202256.html
Ticlopidine •
Systemic - U.S. Brands: Ticlid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202637.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.
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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. 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 Institute12: •
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
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
12
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 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:14 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
13
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). 14 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway15 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.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “atherosclerosis” (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 80950 1303 769 83 10 83115
HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 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.19 Simply search by “atherosclerosis” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
15
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
16
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). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19
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 Biologists20 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.21 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.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Atherosclerosis In the following section, we will discuss databases and references which relate to the Genome Project and atherosclerosis. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).23 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information.
20 Adapted 21
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. 22 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. 23 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “atherosclerosis” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for atherosclerosis: •
Atherosclerosis Susceptibility Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?108725
•
Atherosclerosis, Premature, with Deafness, Nephropathy, Diabetes Mellitus, Photomyoclonus, and Degenerative Neurologic Disease Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?209010 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
•
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
•
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
•
Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
•
Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease,
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Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html •
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
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To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “atherosclerosis” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database24 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database25 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “atherosclerosis” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
24 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 25 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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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 atherosclerosis 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 atherosclerosis. 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 atherosclerosis. 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 “atherosclerosis”:
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Other guides Circulatory Disorders http://www.nlm.nih.gov/medlineplus/circulatorydisorders.html Coronary Disease http://www.nlm.nih.gov/medlineplus/coronarydisease.html Heart Attack http://www.nlm.nih.gov/medlineplus/heartattack.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.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 atherosclerosis. 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: •
Cholesterol: Thinking About Lowering Your Cholesterol Source: Midland, MI: Health Enhancement Systems. 1999. [2 p.]. Contact: Available from Health Enhancement Systems. P.O. Box 1035, Midland, MI 48641-1035. (800) 326-2317 or (517) 839-0852. Fax (517) 839-0025. E-mail:
[email protected]. Website: www.hesonline.com. PRICE: $.68 each; discounts available in bulk orders; Item number: HESHC-1. Summary: Cholesterol is a fat-like substance in the blood that the body needs for many essential functions. High blood cholesterol levels increase the risk of atherosclerosis, a buildup of fatty deposits in the arteries, which makes it difficult for blood to travel through the body. This simple brochure asks readers to consider their current cholesterol levels and to think about making cholesterol control part of an overall plan for better health. The brochure outlines the importance of better cholesterol management. The brochure also has blank space for readers to record their thoughts about lowering their cholesterol and how to overcome the typical obstacles to making changes in one's habits. The brochure concludes with a brief list of resources for readers wanting additional information.
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Thinking About Lowering Your Cholesterol Source: Midland, MI: Health Enhancement Systems. 1999. 2 p. Contact: Available from Health Enhancement Systems. P.O. Box 1035, Midland, MI 48641-1035. (800) 326-2317. Fax (517) 839-0025. PRICE: $0.68 each for a pack of 10 to 50 brochures; bulk quantities available; plus shipping and handling. Item number HESHC1. Summary: This brochure guides readers through the process of thinking about lowering their cholesterol. Cholesterol is a fat like substance that the body needs for many functions, and the liver produces all the cholesterol the body requires. Cholesterol and blood do not mix, so cholesterol needs to be carried in the blood, by fat and protein, in packages called lipoproteins. High density lipoprotein takes cholesterol out of the bloodstream and back to the liver, but low density lipoprotein leaves cholesterol deposits in the walls of the arteries. The brochure begins by explaining the importance of reducing high cholesterol levels. High blood cholesterol levels increase the risk of atherosclerosis, a buildup of fatty deposits in the arteries. This can result in chest pain, heart attacks, and strokes. In addition, the brochure asks a series of questions that helps readers think about lowering cholesterol. The brochure includes a list of helpful organizations.
•
Men: Protect Your Heart Source: Santa Cruz, CA: EAR Associates. 2000. [4 p.]. Contact: Available from EAR Associates. P.O. Box 1830, Santa Cruz, CA 95061-1830. (800) 321-4407. Fax (800) 435-8433. Website: www.etr.org. PRICE: $1.00 plus shipping and handling; bulk orders available. Summary: This brochure provides men with guidelines on preventing heart problems. In heart disease, atherosclerosis causes a blockage in the coronary arteries. Over time, the blockage causes various problems, including stiffening and narrowing of the arteries. The brochure lists risk factors for heart disease that men can and cannot change and lists the warning signs of heart problems. In addition, the brochure presents steps men can take to protect their heart; advises them to get checked for diabetes, high blood pressure, and high cholesterol levels; and offers some tips for making changes to improve heart health.
•
Women: Protect Your Heart Source: Santa Cruz, CA: EAR Associates. 1999. [7 p.]. Contact: Available from EAR Associates. P.O. Box 1830, Santa Cruz, CA 95061-1830. (800) 321-4407. Fax (800) 435-8433. Website: www.etr.org. PRICE: $1.00 plus shipping and handling; bulk orders available. Summary: This brochure provides women with guidelines on preventing heart problems. In heart disease, atherosclerosis causes a blockage in the coronary arteries. Over time, the blockage causes various problems, including stiffening and narrowing of the arteries. The brochure lists risk factors for heart disease that women can and cannot change and lists the warning signs of heart problems. In addition, the brochure presents steps women can take to keep their heart healthy, including quitting smoking and getting checked for diabetes, high blood pressure, and high cholesterol levels. Other topics include ways of making changes to improve heart health.
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Lupus Guide Patient Information Handouts: Serious Conditions Associated With Lupus Source: Bethesda, MD: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1998. 2 p. Contact: Available from National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Information Clearinghouse. 1 AMS Circle, Bethesda, MD 20892-3675. (877) 226-4267 or (301) 495-4484. Fax (301) 718-6366. TTY (301) 565-2966. E-mail:
[email protected]. Website: www.niams.nih.gov. PRICE: Available only as part of a package of patient information sheets; single copy of package free. Order Number: AR-205. Summary: This fact sheet provides people who have systemic lupus erythematosus and the patient care team with information about the serious conditions associated with lupus. Serious conditions caused by or associated with lupus include kidney disease, pericarditis, myocarditis, atherosclerosis, pleuritis, central nervous system disease, depression, osteonecrosis, pancreatitis, acute abdomen, and vision problems. The fact sheet describes these conditions and outlines their warning signs. In addition, the fact sheet provides space for making additional notes.
•
Garlic: Effects on Cardiovascular Risks and Disease, Protective Effects Against Cancer, and Clinical Adverse Effects Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine Clearinghouse. 2000. 7 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL:
[email protected]. PRICE: Free. Publication Number: D153. Summary: This fact sheet summarizes the evidence report on garlic developed by the Agency for Healthcare Research and Quality. It contains a systematic review of clinical studies of garlic in humans. Three major areas are addressed: (1) Effects on cardiovascular-related disease and factors such as lipids, blood pressure, glucose, atherosclerosis, and thrombosis; (2) Any protective associations with cancer; and (3) Clinical adverse effects. The fact sheet includes sections on the search strategy, selection criteria, data collection and analysis, cardiovascular-related outcomes, associations with cancer, adverse effects, conclusions, limitations, and future research.
•
Skin Care and Common Skin Problems Source: Alexandria, VA: American Diabetes Association. 199x. 4 p. Contact: Available from American Diabetes Association, Inc. Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. PRICE: $9.95 (members), $11.95 (nonmembers) for 50 copies; single copy free. Order number CDBD32. Summary: This fact sheet, which is one in a series of 42 fact sheets about daily living and coping with diabetes, provides information on skin care and common skin problems. The fact sheet notes that as many as a third of people with diabetes will have a skin disorder caused or affected by diabetes at some point. Most skin conditions can be prevented or easily treated if caught early. The fact sheet suggests keeping diabetes well controlled; keeping skin clean and dry; avoiding hot baths and showers; preventing dry
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skin; treating cuts immediately; maintaining a more humid atmosphere during colder, drier months; using mild shampoos and unscented soaps; consulting a dermatologist if necessary; and maintaining good foot care. Topics include bacterial infections, fungal infections, itching, diabetic dermopathy, necrobiosis lipoidica diabeticorum, atherosclerosis, allergic reactions, diabetic blisters (bullosis diabeticorum), eruptive xanthomatosis, digital sclerosis, disseminated granuloma annulare, acanthosis nigricans, and good skin care. (AA-M). •
Erectile Dysfunction Source: American Family Physician. 60(4): 1169. September 15, 1999. Contact: Available from American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 274-2237. Website: www.aafp.org. Summary: With the introduction of effective drug treatment for erectile dysfunction (ED, previously called impotence), more men are seeking treatment. This patient education fact sheet accompanies an article that reviews the newer pharmacologic alternatives for ED. Written in question and answer format, the fact sheet discusses ED and its causes, the role of drug treatments, and other non-drug therapies for ED, including vacuum pump devices or surgery. Readers are reminded that ED does not have to be a part of aging, even though there are changes in erectile function that accompany aging. Medical problems that can cause ED include diabetes, high blood pressure (hypertension), and atherosclerosis (hardening of the arteries). Drinking too much, smoking too much, and abusing drugs can also cause ED. 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 atherosclerosis. 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/
282 Atherosclerosis
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: 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 atherosclerosis. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with atherosclerosis. 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 atherosclerosis. 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 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 “atherosclerosis” (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 “atherosclerosis”. 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 “atherosclerosis” (or synonyms) into the “For
Patient Resources
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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 “atherosclerosis” (or a synonym) into the search box, and click “Submit Query.”
285
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.26
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
26
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
286 Atherosclerosis
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)27: •
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/
27
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/
288 Atherosclerosis
•
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/
Finding Medical Libraries
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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/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
290 Atherosclerosis
•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
291
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on atherosclerosis: •
Basic Guidelines for Atherosclerosis Atherosclerosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000171.htm Cerebrovascular disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000726.htm
•
Signs & Symptoms for Atherosclerosis Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm High blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003082.htm Obesity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003101.htm
292 Atherosclerosis
Overweight Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003101.htm •
Diagnostics and Tests for Atherosclerosis Angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm Arteriography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Dialysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003421.htm HDL Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003496.htm LDL Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003495.htm Pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm
•
Nutrition for Atherosclerosis Cholesterol Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002472.htm Fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002468.htm Fats Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002468.htm Low-fat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002468.htm Nicotinic acid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002409.htm
Online Glossaries 293
•
Surgery and Procedures for Atherosclerosis Angioplasty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002953.htm Balloon angioplasty Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002953.htm
•
Background Topics for Atherosclerosis Clot Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001124.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Heart disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000147.htm Kidney disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000457.htm Smoking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002032.htm Stenting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002303.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
295
ATHEROSCLEROSIS 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 fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acanthosis Nigricans: A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]
ACE Inhibitor: A type of drug used to lower blood pressure. Studies indicate that it may also help prevent or slow the progression of kidney disease in people with diabetes. [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] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Actin: Essential component of the cell skeleton. [NIH] 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] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [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
296 Atherosclerosis
and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Kinase: An enzyme that catalyzes the phosphorylation of AMP to ADP in the presence of ATP or inorganic triphosphate. EC 2.7.4.3. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescent Nutrition: Nutrition of children aged 13-18 years. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Aetiology: Study of the causes of disease. [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]
Dictionary 297
Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age Distribution: The frequency of different ages or age groups in a given population. The distribution may refer to either how many or what proportion of the group. The population is usually patients with a specific disease but the concept is not restricted to humans and is not restricted to medicine. [NIH] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agonistic Behavior: Any behavior associated with conflict between two individuals. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [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] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergens: Antigen-type substances (hypersensitivity, immediate). [NIH]
that
produce
immediate
hypersensitivity
Allograft: An organ or tissue transplant between two humans. [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]
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Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alprenolol: 1-((1-Methylethyl)amino)-3-(2-(2-propenyl)phenoxy)-2-propanol. Adrenergic beta-blocker used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. [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] Alveolar Bone Loss: The resorption of bone in the supporting structures of the maxilla or mandible as a result of periodontal disease. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amputation: Surgery to remove part or all of a limb or appendage. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [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] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses.
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[NIH]
Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgenic: Producing masculine characteristics. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] 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] Angiogram: An x-ray of blood vessels; the person receives an injection of dye to outline the vessels on the x-ray. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [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]
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Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anode: Electrode held at a positive potential with respect to a cathode. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]
Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]
Antiandrogens: Drugs used to block the production or interfere with the action of male sex hormones. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibodies, Anticardiolipin: Antiphospholipid antibodies found in association with systemic lupus erythematosus (lupus erythematosus, systemic), antiphospholipid syndrome, and in a variety of other diseases as well as in healthy individuals. The antibodies are detected by solid-phase immunoassay employing the purified phospholipid antigen cardiolipin. [NIH] Antibodies, Antiphospholipid: Autoantibodies directed against phospholipids. These antibodies are characteristically found in patients with systemic lupus erythematosus, antiphospholipid syndrome, related autoimmune diseases, some non-autoimmune diseases, and also in healthy individuals. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antidiabetic Agent: A substance that helps a person with diabetes control the level of glucose (sugar) in the blood so that the body works as it should. [NIH]
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Antidote: A remedy for counteracting a poison. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiphospholipid Syndrome: The presence of antibodies directed against phospholipids (antibodies, antiphospholipid). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (antibodies, anticardiolipin). Present also are high levels of lupus anticoagulant (lupus coagulation inhibitor). [NIH] Antipruritic: Relieving or preventing itching. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle. [NIH] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [NIH]
Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apolipoproteins A: Lipoproteins found in human blood serum in the high-density and very-high-density lipoprotein fraction (HDL, VHDL). They consist of several different
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polypeptides, the most important of which are apolipoprotein A-I and A-II. They maintain the structural integrity of the HDL particles and are activators of lecithin:cholesterol acyltransferase (LCAT). Atherosclerotic patients show low apolipoprotein A levels and these apolipoproteins are either absent or present in extremely low plasma concentration in Tangier disease. [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] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginase: A ureahydrolase that catalyzes the hydrolysis of arginine or canavanine to yield L-ORNITHINE and urea. Deficiency of this enzyme causes hyperargininemia. EC 3.5.3.1. [NIH]
Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogenproducing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriography: A procedure to x-ray arteries. The arteries can be seen because of an injection of a dye that outlines the vessels on an x-ray. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU]
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Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] 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]
Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspartate: A synthetic amino acid. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH] Atherectomy: Endovascular procedure in which atheromatous plaque is excised by a cutting or rotating catheter. It differs from balloon and laser angioplasty procedures which enlarge vessels by dilation but frequently do not remove much plaque. If the plaque is removed by surgical excision under general anesthesia rather than by an endovascular procedure through a catheter, it is called endarterectomy. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition,
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or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [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] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [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] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [NIH] Autopsy: Postmortem examination of the body. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]
Axillary Artery: The continuation of the subclavian artery; it distributes over the upper limb, axilla, chest and shoulder. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH]
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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] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]
Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Baths: The immersion or washing of the body or any of its parts in water or other medium for cleansing or medical treatment. It includes bathing for personal hygiene as well as for medical purposes with the addition of therapeutic agents, such as alkalines, antiseptics, oil, etc. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Betablocker: A drug that induces adrenergic blockade at either ß1- or ß2-adrenergic receptors or at both. [EU] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bezafibrate: Antilipemic agent that lowers cholesterol and triglycerides. It decreases low density lipoproteins and increases high density lipoproteins. [NIH] Bicalutamide: An anticancer drug that belongs to the family of drugs called antiandrogens. [NIH]
Bilateral: Affecting both the right and left side of body. [NIH]
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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 Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [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] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [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] Biomechanics: The study of the application of mechanical laws and the action of forces to living structures. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [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] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in
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an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [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]
Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Artery: The continuation of the axillary artery; it branches into the radial and ulnar arteries. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Diseases: Pathologic conditions affecting the brain, which is composed of the intracranial components of the central nervous system. This includes (but is not limited to) the cerebral cortex; intracranial white matter; basal ganglia; thalamus; hypothalamus; brain
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stem; and cerebellum. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Brain Stem Infarctions: Infarctions that occur in the brain stem which is comprised of the midbrain, pons, and medulla. There are several named syndromes characterized by their distinctive clinical manifestations and specific sites of ischemic injury. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning. [NIH]
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Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [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] Carboxy: Cannabinoid. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] 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] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH]
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Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [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] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] 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] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [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] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Cavernous Sinus: An irregularly shaped venous space in the dura mater at either side of the sphenoid bone. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH]
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Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell 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 Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [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] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Angiography: Radiography of the vascular system of the brain after injection of a contrast medium. [NIH] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU]
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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] 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] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Choleretic: A choleretic agent. [EU] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [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] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [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 Obstructive Pulmonary Disease: Collective term for chronic bronchitis and
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emphysema. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] 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] 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] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Claudication: Limping or lameness. [EU] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] 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] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colestipol: Highly crosslinked and insoluble basic anion exchange resin used as anticholesteremic. It may also may reduce triglyceride levels. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all
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consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] 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)
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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] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Connective Tissue Diseases: A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH]
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Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraception: Use of agents, devices, methods, or procedures which diminish the likelihood of or prevent conception. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [NIH]
Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [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] Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] 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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU]
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Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]
Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried 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] Coronary Vessels: The veins and arteries of the heart. [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] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Criterion: A standard by which something may be judged. [EU] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] 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] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with cyclins to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events. [NIH]
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Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytopenia: A reduction in the number of blood cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH]
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Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decubitus: An act of lying down; also the position assumed in lying down. [EU] Decubitus Ulcer: An ulceration caused by prolonged pressure in patients permitted to lie too still for a long period of time. The bony prominences of the body are the most frequently affected sites. The ulcer is caused by ischemia of the underlying structures of the skin, fat, and muscles as a result of the sustained and constant pressure. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
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Dental Hygienists: Persons trained in an accredited school or dental college and licensed by the state in which they reside to provide dental prophylaxis under the direction of a licensed dentist. [NIH] Dental Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Deoxycholic Acid: A bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH]
DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [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] DHEA: Dehydroepiandrosterone. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Foot: Ulcers of the foot as a complication of diabetes. Diabetic foot, often with infection, is a common serious complication of diabetes and may require hospitalization and disfiguring surgery. The foot ulcers are probably secondary to neuropathies and vascular problems. [NIH] Diabetic Ketoacidosis: Complication of diabetes resulting from severe insulin deficiency coupled with an absolute or relative increase in glucagon concentration. The metabolic acidosis is caused by the breakdown of adipose stores and resulting increased levels of free fatty acids. Glucagon accelerates the oxidation of the free fatty acids producing excess ketone bodies (ketosis). [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH]
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Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diastolic blood pressure: The minimum pressure that remains within the artery when the heart is at rest. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [NIH]
Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or 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 system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] 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] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] 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
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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] 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] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] 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] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart
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and surrounding tissues. The standard approach is transthoracic. [NIH] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [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] 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] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] 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] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory
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laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]
Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [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 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] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endoderm: The inner of the three germ layers of the embryo. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic 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] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components
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from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enterohepatic: Of or involving the intestine and liver. [EU] Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines into portal circulation, passage back into liver, and re-excretion in bile. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]
for
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most
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species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]
Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [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] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU]
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Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Failure to Thrive: A condition in which an infant or child's weight gain and growth are far below usual levels for age. [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] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which are hip fractures. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetal Development: Morphologic and physiologic growth and development of the
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mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolysis: The natural enzymatic dissolution of fibrin. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filipin: A complex of polyene antibiotics obtained from Streptomyces filipinensis. Filipin III alters membrane function by interfering with membrane sterols, inhibits mitochondrial respiration, and is proposed as an antifungal agent. Filipins I, II, and IV are less important. [NIH]
Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Flatus: Gas passed through the rectum. [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] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Foot Care: Taking special steps to avoid foot problems such as sores, cuts, bunions, and calluses. Good care includes daily examination of the feet, toes, and toenails and choosing shoes and socks or stockings that fit well. People with diabetes have to take special care of
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their feet because nerve damage and reduced blood flow sometimes mean they will have less feeling in their feet than normal. They may not notice cuts and other problems as soon as they should. [NIH] Foot Ulcer: Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [NIH] Gamma-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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [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 preparations, and in the manufacturing of capsules and suppositories. [NIH] Gemfibrozil: A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [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]
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Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [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] 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] Genetic transcription: The process by which the genetic information encoded in the gene, represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less
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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] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
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] Glycodeoxycholic Acid: A bile salt formed in the liver by conjugation of deoxycholate with glycine, usually as the sodium salt. It acts as a detergent to solubilize fats for absorption and is itself absorbed. It is used as a cholagogue and choleretic. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [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] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU]
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Gonadorelin: A decapeptide hormone released by the hypothalamus. It stimulates the synthesis and secretion of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. [NIH] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] 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] Grading: A system for classifying cancer cells in terms of how abnormal they appear when examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [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] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] 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] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] 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] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU]
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Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [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]
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Hemorheology: The study of the flow of blood in relation to the pressures, flow, volumes, and resistances in blood vessels in macroscopic, microscopic, and submicroscopic dimensions. [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 and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocyte: A liver cell. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [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] 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]
High blood cholesterol: Cholesterol is the most abundant steroid in animal tissues, especially in bile and gallstones. The relationship between the intake of cholesterol and its manufacture by the body to its utilization, sequestration, or excretion from the body is called the cholesterol balance. When cholesterol accumulates, the balance is positive; when it declines, the balance is negative. In 1993, the NHLBI National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults issued an updated set of recommendations for monitoring and treatment of blood cholesterol levels. The NCEP guidelines recommended that total cholesterol levels and subfractions of high-density lipoprotein (HDL) cholesterol be measured beginning at age 20 in all adults, with subsequent periodic screenings as needed. Even in the group of patients at lowest risk for coronary heart disease (total cholesterol 200 mg/dL and HDL 35 mg/dL), the NCEP recommended that rescreening take place at least once every 5 years or upon physical examination. [NIH] High-density lipoproteins: Lipoproteins that contain a small amount of cholesterol and carry cholesterol away from body cells and tissues to the liver for excretion from the body. Low-level HDL increases the risk of heart disease, so the higher the HDL level, the better. The HDL component normally contains 20 to 30 percent of total cholesterol, and HDL levels are inversely correlated with coronary heart disease risk. [NIH]
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Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair. [NIH]
Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeopathic remedies: Small doses of medicines, herbs, or both that are believed to stimulate the immune system. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homicide: The killing of one person by another. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic 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]
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Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] 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] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperandrogenism: A state characterized or caused by an excessive secretion of androgens by the adrenal cortex, ovaries, or testes. The clinical significance in males is negligible, so the term is used most commonly with reference to the female. The common manifestations in women are hirsutism and virilism. It is often caused by ovarian disease (particularly the polycystic ovary syndrome) and by adrenal diseases (particularly adrenal gland hyperfunction). [NIH] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycaemia: Abnormally increased content of sugar in the blood. [EU] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of
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exposure to challenging antigen due to the release of histamine which follows the antigenantibody reaction and causes smooth muscle contraction and increased vascular permeability. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Hypobetalipoproteinemia: A disease in which the low density lipoprotein (betalipoprotein) concentrations are far below normal. [NIH] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypolipidemic: A drug that lowers abnormally high plasma concentrations of cholesterol or triglycerides or both. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] 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] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterectomy: Excision of the uterus. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH]
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Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immersion: The placing of a body or a part thereof into a liquid. [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] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [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] Immunosuppressive: Describes the ability to lower immune system responses. [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] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a
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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]
Inferior vena cava: A large vein that empties into the heart. It carries blood from the legs and feet, and from organs in the abdomen and pelvis. [NIH] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or
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silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [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] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-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-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intravenous: IV. Into a vein. [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]
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Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] Islet: Cell producing insulin in pancreas. [NIH] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [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] Keratolytic: An agent that promotes keratolysis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the
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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] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
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] 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] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH]
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Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Leuprolide: A potent and long acting analog of naturally occurring gonadotropin-releasing hormone (gonadorelin). Its action is similar to gonadorelin, which regulates the synthesis and release of pituitary gonadotropins. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a
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correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH] 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] Lipoxygenase Inhibitors: Compounds or agents that combine with lipoxygenase and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of the eicosanoid products hydroxyeicosatetraenoic acid and various leukotrienes. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [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] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [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] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lycopene: A red pigment found in tomatoes and some fruits. [NIH]
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Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [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] 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] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysophospholipids: Derivatives of phosphatidic acids that lack one of its fatty acyl chains due to its hydrolytic removal. [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] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Angiography: Non-invasive method of vascular imaging and determination of internal anatomy without injection of contrast media or radiation exposure. The technique is used especially in cerebral angiography as well as for studies of other vascular structures. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] 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] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
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Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] 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] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medroxyprogesterone: (6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [NIH] Medroxyprogesterone Acetate: An injectable contraceptive, generally marketed under the name Depo-Provera. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Melanin: The substance that gives the skin its color. [NIH] Melanosis: Disorders of increased melanin pigmentation that develop without preceding inflammatory disease. [NIH] Membrane: A very thin layer of tissue that covers a surface. [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] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal
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tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltestosterone: A synthetic hormone used for androgen replacement therapy and as an hormonal antineoplastic agent. [NIH] Metoprolol: Adrenergic beta-1-blocking agent with no stimulatory action. It is less bound to plasma albumin than alprenolol and may be useful in angina pectoris, hypertension, or cardiac arrhythmias. [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] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH]
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Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Midaxillary line: An imaginary vertical line that passes midway between the anterior and posterior axillary (armpit) folds. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] 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] Mitotic: Cell resulting from mitosis. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which
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the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [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] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Monounsaturated fat: An unsaturated fat that is found primarily in plant foods, including olive and canola oils. [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] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
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Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [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] Myalgia: Pain in a muscle or muscles. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myelosuppression: A condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets. Myelosuppression is a side effect of some cancer treatments. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]
Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU]
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Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] 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] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrobiosis Lipoidica: A degenerative disease of the dermal connective tissue characterized by the development of erythematous papules or nodules in the pretibial area. The papules form plaques covered with telangiectatic vessels. More than half of the affected patients have diabetes. [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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis,
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as the neutral arch. [EU] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] 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] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] 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] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood
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cell. [NIH] Neutrophil: A type of white blood cell. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nisoldipine: 1,4-Dihydro-2,6-dimethyl-4 (2-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-methylpropyl ester. Nisoldipine is a dihydropyridine calcium channel antagonist that acts as a potent arterial vasodilator and antihypertensive agent. It is also effective in patients with cardiac failure and angina. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nitroglycerin: A highly volatile organic nitrate that acts as a dilator of arterial and venous smooth muscle and is used in the treatment of angina. It provides relief through improvement of the balance between myocardial oxygen supply and demand. Although total coronary blood flow is not increased, there is redistribution of blood flow in the heart when partial occlusion of coronary circulation is effected. [NIH] Nitrous Oxide: Nitrogen oxide (N2O). A colorless, odorless gas that is used as an anesthetic and analgesic. High concentrations cause a narcotic effect and may replace oxygen, causing death by asphyxia. It is also used as a food aerosol in the preparation of whipping cream. [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] Norethindrone: A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with
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nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] 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] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [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]
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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] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteonecrosis: Death of a bone or part of a bone, either atraumatic or posttraumatic. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Ovariectomy: The surgical removal of one or both ovaries. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [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
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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] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] 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] Pancreas Transplant: A surgical procedure that involves replacing the pancreas of a person who has diabetes with a healthy pancreas that can make insulin. The healthy pancreas comes from a donor who has just died or from a living relative. A person can donate half a pancreas and still live normally. [NIH] Pancreas Transplantation: The transference of a pancreas from one human or animal to another. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
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Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Care Team: Care of patients by a multidisciplinary team usually organized under the leadership of a physician; each member of the team has specific responsibilities and the whole team contributes to the care of the patient. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perennial: Lasting through the year of for several years. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH]
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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] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [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] 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 mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Peroxisome Proliferators: A class of nongenotoxic carcinogens that induce the production of hepatic peroxisomes and induce hepatic neoplasms after long-term administration. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] 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] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [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] Phenyl: Ingredient used in cold and flu remedies. [NIH]
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Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phlebotomy: The letting of blood from a vein. Although it is one of the techniques used in drawing blood to be used in diagnostic procedures, in modern medicine, it is used commonly in the treatment of erythrocytosis, hemochromocytosis, polycythemia vera, and porphyria cutanea tarda. Its historical counterpart is bloodletting. (From Cecil Textbook of Medicine, 19th ed & Wintrobe's Clinical Hematology, 9th ed) Venipuncture is not only for the letting of blood from a vein but also for the injecting of a drug into the vein for diagnostic analysis. [NIH] Phosphatidic Acids: Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [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] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected
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to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activator Inhibitor 1: A member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists
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in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]
Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Podiatrist: A doctor who treats and takes care of people's feet. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] Polydipsia: Chronic excessive thirst, as in diabetes mellitus or diabetes insipidus. [EU] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] 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]
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Polyphagia: Great hunger; a sign of diabetes. People with this great hunger often lose weight. [NIH] Polyphosphates: Linear polymers in which orthophosphate residues are linked with energy-rich phosphoanhydride bonds. They are found in plants, animals, and microorganisms. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyuria: Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]
Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] 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] Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase
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(hydroxymethylglutaryl CoA reductases). [NIH] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Premenopausal: Refers to the time before menopause. Menopause is the time of life when a women's menstrual periods stop permanently; also called "change of life." [NIH] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary endpoint: The main result that is measured at the end of a study to see if a given treatment worked (e.g., the number of deaths or the difference in survival between the treatment group and the control group). What the primary endpoint will be is decided before the study begins. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] 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] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [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] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU]
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Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [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] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH]
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Protein 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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]
Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychoneuroimmunology: The field concerned with the interrelationship between the brain, behavior and the immune system. Neuropsychologic, neuroanatomic and psychosocial studies have demonstrated their role in accentuating or diminishing immune/allergic responses. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among
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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 hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyrogenic: Inducing fever. [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation 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] Radioactive: Giving off radiation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays,
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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] Raloxifene: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue. [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] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] 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] 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] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [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] 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] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and
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relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] 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,
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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] Retinal Vein: Central retinal vein and its tributaries. It runs a short course within the optic nerve and then leaves and empties into the superior ophthalmic vein or cavernous sinus. [NIH]
Retinal Vein Occlusion: Occlusion of the retinal vein. Those at high risk for this condition include patients with hypertension, diabetes mellitus, arteriosclerosis, and other cardiovascular diseases. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [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] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Rosiglitazone: A drug taken to help reduce the amount of sugar in the blood. Rosiglitazone helps make insulin more effective and improves regulation of blood sugar. It belongs to the family of drugs called thiazolidinediones. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH]
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Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Saturate: Means fatty acids without double bond. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schematic: Representative or schematic eye computed from the average of a large number of human eye measurements by Allvar Gullstrand. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [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] Scrotum: In males, the external sac that contains the testicles. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [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] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [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
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as epilepsy or "seizure disorder." [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the
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circulation, which can upset all body functions: sometimes referred to as circulatory shock. [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] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. [NIH] Skin Care: Maintenance of the hygienic state of the skin under optimal conditions of cleanliness and comfort. Effective in skin care are proper washing, bathing, cleansing, and the use of soaps, detergents, oils, etc. In various disease states, therapeutic and protective solutions and ointments are useful. The care of the skin is particularly important in various occupations, in exposure to sunlight, in neonates, and in decubitus ulcer. [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]
Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH] Social Behavior: Any behavior caused by or affecting another individual, usually of the
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same species. [NIH] Social Conditions: The state of society as it exists or in flux. While it usually refers to society as a whole in a specified geographical or political region, it is applicable also to restricted strata of a society. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [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] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [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
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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] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] 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] 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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Stanozolol: Anabolic agent. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] 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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or
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tension. Stress may be either physical or psychologic, or both. [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] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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] Subtrochanteric: Below a trochanter. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] 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] Supplementation: Adding nutrients to the diet. [NIH] Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. [NIH] Surgery, Plastic: The branch of surgery concerned with restoration, reconstruction, or improvement of defective, damaged, or missing structures. [NIH]
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Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] 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] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Systolic pressure: The highest pressure to which blood pressure rises with the contraction of the ventricles. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [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] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH]
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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] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombopenia: Reduction in the number of platelets in the blood. [NIH] Thromboses: The formation or presence of a blood clot within a blood vessel during life. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU]
378 Atherosclerosis
Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [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 Transplantation: Transference of tissue within an individual, between individuals of the same species, or between individuals of different species. [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] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxaemia: 1. The condition resulting from the spread of bacterial products (toxins) by the bloodstream. 2. A condition resulting from metabolic disturbances, e.g. toxaemia of pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] 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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the
Dictionary 379
initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [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] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Triad: Trivalent. [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] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Troglitazone: A drug used in diabetes treatment that is being studied for its effect on reducing the risk of cancer cell growth in fat tissue. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [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] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH]
380 Atherosclerosis
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. 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 Intima: The innermost coat of blood vessels, consisting of a thin lining of endothelial cells longitudinally oriented and continuous with the endothelium of capillaries on the one hand and the endocardium of the heart on the other. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Ultrasound test: A test that bounces sound waves off tissues and internal organs and changes the echoes into pictures (sonograms). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Univalent: Pertaining to an unpaired chromosome during the zygotene stage of prophase to first metaphase in meiosis. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the
Dictionary 381
deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [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] 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] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]
Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] 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] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH]
382 Atherosclerosis
Vegetarianism: Dietary practice of consuming only vegetables, grains, and nuts. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Vena: A vessel conducting blood from the capillary bed to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [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] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [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] Virilism: Development of masculine traits in the female. [NIH] Virilization: The induction or development of male secondary sec characters, especially the induction of such changes in the female, including enlargement of the clitoris, growth of facial and body hair, development of a hairline typical of the male forehead, stimulation of secretion and proliferation of the sebaceous glands (often with acne), and deepening of the voice. Called also masculinization) [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] 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] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Void: To urinate, empty the bladder. [NIH]
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Waist circumference: To define the level at which the waist circumference is measured, a bony landmark is first located and marked. The subject stands, and the technician, positioned to the right of the subject, palpates the upper hip bone to locate the right ileum. Just above the uppermost lateral border of the right ileum, a horizontal mark is drawn and then crossed with a vertical mark on the midaxillary line. The measuring tape is then placed around the trunk, at the level of the mark on the right side, making sure that it is on a level horizontal plane on all sides. The tape is then tightened slightly without compressing the skin and underlying subcutaneous tissues. The measure is recorded in centimeters to the nearest millimeter. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] War: Hostile conflict between organized groups of people. [NIH] Weight Gain: Increase in body weight over existing weight. [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]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthomatosis: A condition of morphologic change in which there is accumulation of lipids in the large foam cells of tissues. It is the cutaneous manifestation of lipidosis in which plasma fatty acids and lipoproteins are quantitatively changed. The xanthomatous eruptions have several different distinct morphologies dependent upon the specific form taken by the disease. [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] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
385
INDEX A Abdomen, 280, 295, 306, 307, 325, 339, 340, 344, 356, 358, 374, 377 Abdominal, 97, 101, 149, 160, 295, 296, 337, 347, 356, 358 Abdominal fat, 160, 295 Aberrant, 41, 192, 231, 295 Ablation, 65, 295 Acanthosis Nigricans, 281, 295 Acatalasia, 295, 310 Acceptor, 295, 343, 355, 379 ACE, 5, 109, 116, 169, 190, 295 ACE Inhibitor, 190, 295 Acetylcholine, 295, 312, 353 Acidosis, 241, 295, 320 Acne, 176, 295, 318, 382 Actin, 62, 295, 351, 352, 379 Acyl, 295, 345 Adaptability, 295, 311 Adduct, 52, 295 Adenine, 295, 296, 366 Adenosine, 86, 195, 196, 295, 296, 308, 359 Adenosine Triphosphate, 86, 196, 296, 359 Adenovirus, 65, 95, 296 Adenylate Kinase, 222, 296 Adipocytes, 230, 296, 315, 342 Adipose Tissue, 160, 179, 295, 296 Adjunctive Therapy, 28, 296 Adjustment, 4, 6, 7, 8, 13, 296 Adjuvant, 23, 68, 213, 296, 329 Adolescent Nutrition, 240, 296 Adrenal Cortex, 296, 317, 326, 336, 363, 368 Adrenal Glands, 296, 298 Adrenergic, 32, 62, 198, 199, 296, 298, 303, 305, 326, 347, 364, 376, 380 Adverse Effect, 7, 213, 280, 296, 372 Aerobic, 296, 348 Aerosol, 296, 353 Aetiology, 250, 296 Afferent, 27, 296, 342 Affinity, 29, 56, 296, 297, 373 Agar, 297, 360 Age Distribution, 33, 297 Age Groups, 297 Age of Onset, 297, 380 Agonist, 297, 353, 367 Agonistic Behavior, 31, 297
Alanine, 51, 297 Albumin, 190, 260, 297, 347, 360 Aldehydes, 39, 297 Alertness, 297, 308 Algorithms, 26, 297, 306 Alkaline, 295, 297, 298, 308, 356, 377 Alkaloid, 297, 353 Alleles, 297, 343 Allergens, 216, 297 Allograft, 89, 297 Alpha Particles, 297, 366 Alpha-1, 259, 298, 359 Alprenolol, 298, 347 Alternative medicine, 260, 298 Alveolar Bone Loss, 54, 298 Ameliorated, 176, 298 Ameliorating, 210, 211, 298 Amenorrhea, 298, 300, 353, 361 Amino Acid Sequence, 212, 298, 300, 330 Amino Acids, 224, 234, 298, 299, 330, 352, 357, 361, 365, 369, 371, 375, 379, 380, 381 Ammonia, 213, 298, 380 Amputation, 5, 239, 298 Amyloid, 17, 191, 223, 298 Amyloidosis, 223, 298 Anaesthesia, 298, 339 Anal, 194, 298, 344 Analgesic, 298, 353 Analog, 298, 343 Analytes, 298, 375 Anaphylatoxins, 299, 314 Anatomical, 299, 303, 312, 321, 324, 338, 352, 370 Androgenic, 177, 299, 353 Androgens, 14, 80, 154, 176, 296, 299, 302, 336 Anemia, 138, 219, 299, 328 Anesthesia, 299, 303, 324 Aneurysm, 72, 101, 299, 301, 381 Angina, 28, 33, 135, 151, 174, 178, 210, 216, 219, 224, 232, 233, 299, 347, 353, 364 Angina Pectoris, 28, 216, 219, 232, 233, 299, 347, 364 Angiogenesis, 47, 54, 62, 64, 178, 196, 201, 203, 207, 208, 224, 241, 299, 346 Angiogram, 163, 299 Angiography, 90, 104, 153, 162, 163, 292, 299
386 Atherosclerosis
Angioplasty, 4, 79, 167, 169, 174, 216, 234, 293, 299, 303, 350 Angiotensin-Converting Enzyme Inhibitors, 84, 299 Angiotensinogen, 16, 299, 368 Animal model, 16, 23, 30, 31, 35, 37, 41, 50, 54, 57, 63, 67, 86, 175, 189, 211, 299 Anions, 64, 297, 300, 341, 371, 375 Ankle, 10, 300 Annealing, 300, 361 Anode, 300 Anorexia, 219, 241, 300, 380 Anorexia Nervosa, 241, 300 Anovulation, 300, 361 Antagonism, 58, 59, 231, 300, 308 Antecedent, 200, 300 Antiandrogens, 300, 305 Antibacterial, 300, 374 Antibiotic, 23, 73, 86, 300, 357, 374 Antibodies, Anticardiolipin, 300, 301 Antibodies, Antiphospholipid, 300, 301 Anticoagulant, 300, 301, 364 Anticonvulsant, 300, 309 Antidiabetic, 199, 201, 202, 300 Antidiabetic Agent, 199, 202, 300 Antidote, 301, 308 Antifungal, 301, 328 Antigen-Antibody Complex, 301, 314 Antigen-presenting cell, 301, 319 Antihypertensive, 298, 301, 353 Anti-infective, 301, 336, 372 Anti-inflammatory, 7, 11, 14, 203, 235, 301, 330 Anti-Inflammatory Agents, 203, 301 Antimicrobial, 212, 228, 229, 301, 320 Antineoplastic, 301, 329, 347, 361 Antiphospholipid Syndrome, 83, 234, 300, 301 Antipruritic, 301, 312 Anxiety, 219, 239, 254, 301, 364 Aortic Aneurysm, 51, 94, 301 Aortic Valve, 70, 301 Aplastic anemia, 176, 301 Apolipoproteins, 40, 46, 153, 192, 246, 301, 329, 343 Apolipoproteins A, 192, 301 Apoptosis, 22, 49, 52, 59, 112, 113, 119, 120, 133, 195, 199, 201, 213, 220, 302 Aqueous, 302, 305, 318, 324, 336, 342 Arachidonate 12-Lipoxygenase, 302, 344 Arachidonate 15-Lipoxygenase, 302, 344 Arachidonate Lipoxygenases, 302, 344
Arachidonic Acid, 54, 243, 302, 323, 343, 344, 364 Arginase, 16, 302 Arginine, 16, 42, 44, 128, 139, 299, 302, 353, 355 Aromatase, 77, 302 Arrhythmia, 178, 224, 233, 302 Arteriography, 167, 292, 302 Arteriolar, 302, 303, 307, 368 Arterioles, 31, 45, 302, 303, 307, 309, 347, 350, 381 Arteriolosclerosis, 303 Arteriosclerosis, 128, 130, 132, 134, 135, 156, 160, 162, 193, 225, 226, 243, 303, 337, 369 Arteriosus, 303, 366 Arteriovenous, 303, 347 Articular, 303, 355 Ascorbic Acid, 15, 264, 303, 336 Aspartate, 51, 303 Asphyxia, 303, 353 Assay, 48, 57, 60, 108, 114, 115, 121, 131, 186, 187, 225, 303, 380 Asymptomatic, 15, 55, 101, 108, 115, 158, 162, 295, 303, 356 Atenolol, 213, 303 Atherectomy, 243, 303, 324 Atmospheric Pressure, 303, 336 Atrial, 31, 233, 303, 316, 379 Atrioventricular, 303, 316 Atrium, 303, 316, 379, 382 Atrophy, 303, 352 Attenuated, 4, 42, 72, 304 Atypical, 199, 304 Autoantibodies, 108, 115, 300, 304 Autoantigens, 304 Autodigestion, 304, 356 Autoimmune disease, 223, 234, 300, 304, 350 Autoimmunity, 7, 20, 83, 92, 219, 243, 304 Autologous, 68, 187, 304 Autonomic, 84, 99, 238, 240, 295, 304, 353, 357, 373, 376 Autonomic Nervous System, 99, 240, 304, 357, 373, 376 Autonomic Neuropathy, 84, 238, 304 Autopsy, 8, 13, 76, 97, 98, 304 Autoradiography, 57, 304 Axillary, 304, 307, 348 Axillary Artery, 304, 307 B Bacteremia, 53, 229, 304
Index 387
Bacterial Infections, 281, 304 Bacterial toxin, 229, 304 Bactericidal, 212, 304, 326 Bacteriophage, 305, 360, 379 Baroreflex, 27, 305 Basal Ganglia, 305, 307, 308 Basal Ganglia Diseases, 305 Base, 53, 66, 295, 305, 319, 329, 330, 341, 376, 380 Basement Membrane, 305, 327, 342 Basophils, 174, 305, 332, 342 Baths, 280, 305 Benign, 22, 219, 238, 303, 305, 332, 333, 351, 366 Benzene, 305, 341 Betablocker, 213, 305 Beta-pleated, 298, 305 Bezafibrate, 213, 305 Bicalutamide, 177, 305 Bilateral, 305, 361 Bile, 70, 181, 182, 187, 194, 207, 218, 245, 250, 306, 312, 320, 325, 329, 331, 334, 335, 344, 374, 376 Bile Acids, 182, 187, 194, 245, 250, 306, 374, 376 Bile Acids and Salts, 194, 306 Bile Ducts, 306, 329 Biliary, 65, 187, 306, 312, 356 Biliary Tract, 306, 356 Bilirubin, 94, 297, 306, 329 Bioavailability, 306, 338 Biochemical, 14, 34, 55, 129, 250, 297, 306, 331, 355, 371 Biogenesis, 38, 306 Biological therapy, 306, 332 Biomarkers, 56, 306 Biomechanics, 239, 306 Biomolecular, 306, 375 Biopsy, 306, 357 Biosynthesis, 36, 64, 67, 197, 302, 306, 318, 344, 364, 371, 372 Biotechnology, 72, 77, 250, 260, 271, 306 Bladder, 304, 306, 350, 352, 364, 381, 382 Bloating, 306, 338 Blood Coagulation, 306, 307, 308, 328, 377 Blood Glucose, 5, 7, 192, 205, 228, 240, 254, 255, 307, 333, 337, 340 Blood Platelets, 307, 360, 371 Blot, 23, 307 Body Fluids, 306, 307, 308, 373, 380 Body Mass Index, 7, 8, 160, 307, 355 Bone Density, 111, 117, 307
Bone Marrow, 41, 51, 56, 59, 65, 95, 301, 305, 307, 338, 345, 350, 373, 375 Bone Marrow Transplantation, 51, 65, 307 Bone scan, 307, 370 Bowel, 195, 212, 219, 298, 307, 321, 339, 340, 342, 358 Bowel Movement, 307, 321 Brachial, 10, 69, 94, 307 Brachial Artery, 69, 94, 307 Brachytherapy, 307, 340, 341, 366, 383 Bradykinin, 169, 307, 341, 353, 360 Brain Diseases, 180, 307 Brain Infarction, 86, 223, 308 Brain Stem, 308, 311, 352 Brain Stem Infarctions, 308 Branch, 94, 169, 209, 289, 308, 323, 357, 365, 373, 375, 377 Breakdown, 52, 192, 308, 311, 320, 321, 329, 354, 372 Bronchitis, 308, 312 Buccal, 308, 344 Buffers, 305, 308 Bulimia, 219, 308 Bypass, 31, 162, 166, 216, 249, 251, 308, 350 C Cachexia, 195, 219, 308 Caffeine, 240, 308, 366 Calcification, 15, 21, 32, 34, 45, 70, 212, 303, 308 Calcium Chloride, 184, 308 Capillary, 62, 203, 307, 309, 369, 382 Capillary Fragility, 309, 369 Capillary Permeability, 307, 309 Capsules, 7, 309, 322, 329 Captopril, 190, 309 Carbamazepine, 90, 309 Carbohydrate, 148, 241, 309, 331, 362 Carboxy, 233, 309 Carcinogen, 295, 309 Carcinogenesis, 196, 309 Carcinogenic, 305, 309, 339, 363, 374 Carcinoma, 198, 309, 318 Cardiac Output, 305, 309 Cardiology, 5, 14, 78, 79, 80, 86, 87, 89, 92, 93, 94, 104, 105, 109, 116, 128, 130, 169, 309 Cardiomyopathy, 84, 136, 206, 227, 309 Cardioselective, 303, 309, 364 Cardiovascular System, 252, 254, 304, 309 Carnitine, 124, 202, 222, 310 Carotene, 139, 156, 310, 368 Carotenoids, 156, 310
388 Atherosclerosis
Carotid Arteries, 18, 130, 162, 164, 310 Carrier Proteins, 310, 360 Catabolism, 29, 128, 310 Catalase, 27, 295, 310 Catalytic Domain, 233, 310 Cataracts, 136, 202, 205, 206, 310 Catecholamine, 310, 358 Catheterization, 299, 310, 350 Catheters, 153, 310, 338, 340 Causal, 3, 35, 40, 93, 182, 183, 310, 340 Cause of Death, 28, 29, 42, 46, 47, 49, 50, 54, 60, 64, 174, 175, 183, 209, 215, 228, 310 Caustic, 310, 372 Cavernous Sinus, 310, 369 Cell Adhesion, 28, 46, 54, 77, 174, 310 Cell Adhesion Molecules, 28, 310 Cell Count, 7, 310 Cell Cycle, 91, 199, 311, 317, 326, 333 Cell Death, 52, 102, 186, 302, 311, 326, 351 Cell Differentiation, 79, 196, 219, 311, 372 Cell Division, 199, 304, 311, 326, 332, 348, 360 Cell membrane, 186, 226, 310, 311, 320, 341, 359 Cell proliferation, 16, 64, 174, 196, 200, 204, 212, 219, 233, 234, 303, 311, 372 Cell Respiration, 311, 348, 368 Cell Survival, 311, 332 Cellular metabolism, 29, 311 Ceramide, 69, 311 Cerebellum, 308, 311 Cerebral Angiography, 311, 345 Cerebral Arteries, 183, 228, 311 Cerebral hemispheres, 305, 308, 311, 312 Cerebral Infarction, 308, 311 Cerebrospinal, 212, 311 Cerebrospinal fluid, 212, 311 Cerebrovascular, 21, 86, 110, 117, 156, 157, 158, 160, 161, 162, 168, 183, 291, 305, 309, 311 Cerebrum, 311, 312 Character, 226, 299, 312, 319 Chemokines, 22, 37, 215, 216, 312 Chemotactic Factors, 312, 314 Chest Pain, 216, 279, 312 Chimeras, 56, 312 Chin, 73, 111, 118, 312 Choleretic, 312, 320, 331 Cholesterol Esters, 312, 343 Cholestyramine, 218, 264, 312 Cholinergic, 312, 353
Choroid, 312, 316, 368 Chromatin, 186, 302, 312, 325, 374 Chromium, 128, 312 Chromosomal, 24, 43, 44, 312 Chromosome, 44, 45, 312, 315, 343, 380 Chronic Disease, 23, 50, 215, 219, 308, 312 Chronic Obstructive Pulmonary Disease, 136, 174, 223, 312 Chronic renal, 313, 361, 380 Chylomicrons, 131, 184, 187, 313, 343 Circulatory system, 209, 313, 324 CIS, 313, 368 Citrus, 303, 313 Claudication, 137, 155, 241, 313 Clear cell carcinoma, 313, 320 Clinical Medicine, 63, 114, 121, 245, 313, 363 Clinical trial, 13, 40, 151, 161, 167, 170, 209, 250, 271, 313, 316, 349, 365, 367 Clone, 24, 313 Cloning, 24, 72, 306, 313 Coagulation, 40, 49, 252, 301, 306, 313, 334, 360, 377 Coenzyme, 69, 184, 200, 206, 303, 313, 344, 372 Cofactor, 64, 313, 365, 377 Colestipol, 162, 218, 264, 313 Colitis, 195, 196, 201, 212, 313, 339 Collagen, 181, 212, 223, 228, 305, 313, 315, 327, 328, 329, 332, 346, 360, 363 Collapse, 308, 314 Colloidal, 140, 297, 314, 371 Combination Therapy, 167, 181, 194, 314, 326 Complement, 24, 45, 224, 299, 314, 330, 345, 360 Complementary and alternative medicine, 127, 145, 314 Complementary medicine, 127, 314 Computational Biology, 271, 314 Computed tomography, 32, 43, 44, 69, 70, 307, 314, 315, 370 Computerized axial tomography, 314, 315, 370 Computerized tomography, 314, 315 Concomitant, 238, 315 Cone, 315, 359 Confounding, 34, 315 Congestive heart failure, 208, 216, 242, 315 Conjugated, 34, 67, 109, 116, 140, 177, 306, 315, 318, 320, 354 Conjugation, 315, 331
Index 389
Conjunctiva, 315, 339 Conjunctivitis, 174, 315 Connective Tissue, 148, 181, 301, 303, 307, 313, 315, 328, 329, 347, 351, 365, 369, 375, 376 Connective Tissue Cells, 315 Connective Tissue Diseases, 301, 315 Consciousness, 298, 315, 319, 322, 368 Constitutional, 315, 350 Constriction, 315, 341 Consumption, 3, 82, 316, 368 Contamination, 316, 334 Contraception, 316, 353 Contraceptive, 316, 346 Contractility, 299, 316 Contraindications, ii, 316 Contrast Media, 316, 345 Control group, 316, 363 Controlled study, 83, 316 Conus, 316, 366 Conventional therapy, 167, 316 Conventional treatment, 316 Convulsions, 300, 316, 323, 337, 363 Coordination, 311, 316, 350 Cor, 31, 316, 317 Cornea, 316, 331 Coronary Arteriosclerosis, 154, 156, 157, 158, 159, 160, 161, 162, 165, 166, 218, 317, 350 Coronary Artery Bypass, 4, 76, 96, 164, 317 Coronary Circulation, 299, 317, 353 Coronary Disease, 11, 34, 155, 156, 158, 159, 160, 161, 162, 163, 166, 167, 169, 261, 278, 317 Coronary Thrombosis, 317, 347, 350 Coronary Vessels, 317 Corpus, 317, 363 Corpus Luteum, 317, 363 Cortex, 307, 311, 317, 326, 335, 351 Corticosteroids, 10, 13, 317, 330, 348 Corticotropin-Releasing Hormone, 31, 317 Cortisol, 65, 297, 317 Cranial, 311, 317, 333, 352, 354, 357 Creatinine, 28, 54, 317, 380 Criterion, 177, 317 Cultured cells, 45, 317 Curative, 317, 353, 377 Cutaneous, 238, 239, 317, 344, 383 Cyclic, 232, 308, 317, 332, 353, 364 Cyclin, 199, 317 Cyclin-Dependent Kinases, 199, 317
Cyproterone, 318, 328 Cystathionine beta-Synthase, 318, 336 Cysteine, 203, 204, 312, 318, 324, 375 Cystine, 180, 318 Cytochrome, 302, 318 Cytokine, 7, 20, 23, 42, 51, 60, 98, 216, 224, 318 Cytomegalovirus, 32, 165, 169, 318 Cytopenia, 219, 318 Cytoplasm, 302, 305, 311, 318, 325, 332, 352, 369 Cytoskeleton, 188, 318, 348 Cytotoxic, 55, 318, 367, 372 D Dairy Products, 318, 370 Data Collection, 280, 318 Databases, Bibliographic, 271, 318 Deamination, 319, 349, 381 Decubitus, 319, 372 Decubitus Ulcer, 319, 372 Defense Mechanisms, 39, 319 Degenerative, 195, 235, 316, 319, 334, 345, 349, 351, 355, 369 Deletion, 22, 193, 302, 319 Delirium, 219, 319 Delivery of Health Care, 319, 333 Dementia, 10, 180, 219, 319, 352 Denaturation, 319, 361 Dendrites, 319, 352 Dendritic, 20, 26, 319 Dendritic cell, 20, 26, 319 Dental Care, 12, 319 Dental Caries, 229, 319, 320 Dental Hygienists, 12, 320 Dental Plaque, 229, 320 Deoxycholic Acid, 195, 320 Depolarization, 320, 372 Dermal, 320, 351 Dermatitis, 174, 219, 320, 323 Dermatologist, 281, 320 DES, 108, 115, 199, 299, 320 Detergents, 320, 372 DHEA, 88, 141, 320 Diabetes Insipidus, 320, 361 Diabetic Foot, 238, 239, 241, 242, 320 Diabetic Ketoacidosis, 238, 320 Diabetic Retinopathy, 159, 174, 196, 202, 205, 206, 208, 238, 254, 320, 359 Diagnostic procedure, 173, 260, 320, 359 Dialyzer, 320, 333 Diarrhea, 192, 312, 321 Diastole, 26, 321
390 Atherosclerosis
Diastolic, 9, 321, 337 Diastolic blood pressure, 9, 321 Diencephalon, 321, 337, 352, 377 Dietary Fats, 321, 343 Diffusion, 309, 321, 339, 341 Digestion, 306, 307, 321, 322, 338, 340, 343, 344, 374, 381 Digestive system, 171, 321 Digestive tract, 187, 304, 321, 372 Dihydrotestosterone, 198, 321, 367 Dihydroxy, 321, 369 Dilatation, 94, 299, 321, 363, 381 Dilatation, Pathologic, 321, 381 Dilation, 31, 69, 94, 303, 307, 321, 381 Dilator, 321, 353 Dimethyl, 321, 353 Direct, iii, 23, 25, 27, 28, 30, 34, 35, 40, 46, 52, 53, 191, 211, 212, 263, 313, 321, 367 Disease Progression, 16, 32, 167, 321 Disinfectant, 321, 326 Disorientation, 319, 321 Disparity, 99, 321 Dissection, 51, 68, 321 Dissociation, 296, 321 Distal, 51, 317, 322, 358, 365 Diuresis, 308, 322 Diuretic, 6, 308, 322, 373 Diverticulum, 193, 322 Domesticated, 67, 322 Dosage Forms, 197, 322 Drive, ii, vi, 107, 110, 117, 203, 237, 239, 241, 261, 322, 341, 343 Drug Interactions, 265, 322 Drug Tolerance, 322, 378 Duodenum, 306, 322, 374 Dyes, 298, 305, 322 Dyskinesia, 322 Dyslipidemia, 12, 40, 79, 89, 128, 175, 179, 200, 230, 239, 242, 259, 322 Dyspareunia, 322, 326 Dyspepsia, 322, 338 Dystrophy, 195, 196, 322 E Echocardiography, 51, 88, 322 Eclampsia, 323, 363 Eczema, 216, 323 Edema, 137, 190, 320, 323, 342, 350, 351, 363, 380 Effector, 58, 295, 314, 323, 352 Efficacy, 19, 71, 151, 178, 190, 209, 225, 239, 323 Eicosanoids, 54, 246, 323
Elasticity, 25, 303, 317, 323, 372 Elastin, 25, 104, 228, 314, 315, 323, 327 Electrocardiogram, 164, 323 Electrocoagulation, 313, 323 Electrolysis, 300, 323 Electrolyte, 319, 323, 348, 362, 373, 380 Electrons, 301, 305, 323, 341, 355, 366, 367, 375 Embolism, 241, 323 Embolus, 323, 339 Embryo, 311, 323, 324, 328, 330, 339, 347, 361 Emergency Medicine, 238, 323 Emergency Treatment, 323 Emphysema, 313, 323 Empirical, 191, 323 Emulsion, 304, 324 Enalapril, 89, 324 Enamel, 319, 324 Endarterectomy, 250, 299, 303, 324 Endemic, 216, 247, 324, 374 Endocrine System, 324, 352 Endocrinology, 79, 89, 92, 93, 96, 104, 114, 120, 241, 247, 324 Endocytosis, 46, 65, 66, 324 Endoderm, 193, 324 Endometrial, 324 Endometriosis, 188, 324, 353 Endometrium, 324, 346 Endopeptidases, 324, 364 Endothelium, Lymphatic, 324 Endothelium, Vascular, 324 Endothelium-derived, 325, 353 Endotoxic, 195, 196, 325, 343 Endotoxin, 325, 380 End-stage renal, 82, 128, 313, 325, 361 Energy balance, 325, 342 Enhancer, 325, 368 Enterohepatic, 182, 325 Enterohepatic Circulation, 182, 325 Environmental Health, 270, 272, 325 Environmental Pollutants, 61, 325 Enzymatic, 55, 57, 64, 181, 223, 308, 310, 314, 317, 319, 325, 328, 335, 361, 368 Enzyme Inhibitors, 325, 360 Eosinophils, 174, 251, 325, 332, 342 Epidemic, 82, 242, 252, 325, 374 Epidemiological, 17, 40, 113, 120, 157, 182, 184, 325 Epidermal, 188, 325 Epidermal Growth Factor, 188, 325 Epidermis, 325
Index 391
Epigastric, 325, 356 Epinephrine, 296, 325, 353, 380 Epithelial, 192, 325, 326, 342 Epithelial Cells, 325, 326, 342 Epithelium, 305, 324, 326 Epitopes, 63, 326 Erectile, 136, 191, 253, 281, 326 Erection, 253, 326 Erythrocytes, 61, 299, 307, 326, 367 Esophagus, 321, 326, 333, 358, 374 Estradiol, 77, 164, 264, 326 Estrogen, 10, 34, 67, 83, 92, 100, 110, 117, 131, 148, 164, 165, 166, 176, 302, 318, 326, 367, 371 Estrogen receptor, 326 Estrogen Replacement Therapy, 68, 100, 166, 177, 326 Ethanol, 187, 326 Etoposide, 22, 326 Eukaryotic Cells, 326, 380 Evoke, 326, 374 Excitability, 27, 326 Exhaustion, 300, 326 Exocrine, 326, 356 Exogenous, 26, 65, 309, 323, 327, 330, 380 Extensor, 327, 365 External-beam radiation, 327, 341, 366, 383 Extracellular Matrix, 15, 38, 56, 57, 103, 175, 203, 315, 327, 328, 346, 355 Extracellular Matrix Proteins, 57, 327, 346 Extracellular Space, 327, 348 Eye Infections, 296, 327 F Facial, 177, 327, 373, 382 Failure to Thrive, 192, 327 Family Planning, 271, 327 Fatigue, 327, 333 Feces, 194, 327 Femoral, 162, 164, 327, 335 Femoral Artery, 162, 327 Femoral Neck Fractures, 327, 335 Femur, 327, 335 Ferritin, 155, 327 Fetal Development, 34, 327 Fetus, 328, 360, 381 Fibrin, 40, 49, 61, 251, 307, 328, 360, 377 Fibrinogen, 7, 33, 40, 51, 66, 74, 328, 360, 377 Fibrinolysis, 4, 252, 328 Fibrinolytic, 40, 328
Fibroblasts, 178, 213, 225, 234, 315, 328, 340, 349 Fibronectins, 327, 328 Fibrosis, 174, 251, 328, 370 Filipin, 57, 328 Filtration, 184, 328 Flatus, 328, 329 Fluorescence, 57, 194, 328 Flutamide, 177, 328 Foam Cells, 23, 59, 60, 189, 197, 215, 328, 383 Folate, 103, 123, 124, 328 Fold, 6, 13, 49, 66, 69, 176, 328, 347 Folic Acid, 122, 123, 157, 328 Foot Care, 239, 281, 328 Foot Ulcer, 206, 239, 320, 329 Foramen, 312, 329 Forearm, 307, 329 Frameshift, 329, 380 Frameshift Mutation, 329, 380 G Gadolinium, 163, 164, 168, 329 Gallbladder, 295, 306, 321, 329 Gallstones, 221, 306, 329, 334 Gamma-interferon, 329, 340 Ganglia, 295, 305, 329, 351, 357, 376 Gangrene, 209, 295, 329 Gas, 57, 166, 185, 298, 321, 328, 329, 336, 338, 353, 375, 382 Gastric, 194, 304, 310, 322, 325, 329, 333, 335 Gastrin, 329, 335 Gastrointestinal, 174, 192, 194, 198, 199, 238, 307, 326, 329, 343, 371, 373, 374, 375, 380 Gastrointestinal tract, 192, 194, 326, 329, 343, 371, 374, 380 Gelatin, 329, 331, 377 Gemfibrozil, 218, 264, 329 Gene Expression, 19, 20, 35, 41, 48, 56, 58, 70, 75, 195, 196, 201, 330 Gene Targeting, 48, 59, 74, 330 Genetic Code, 330, 354 Genetic Engineering, 74, 306, 313, 330 Genetic testing, 330, 361 Genetic transcription, 330, 363, 379 Genetics, 36, 37, 44, 45, 110, 111, 117, 156, 169, 193, 237, 247, 248, 315, 330 Genital, 304, 313, 330 Genomics, 38, 111, 112, 118, 119, 157, 330 Genotype, 99, 103, 330, 358 Germ Cells, 330, 355, 374, 377
392 Atherosclerosis
Germ Layers, 324, 330 Gestation, 330, 357, 360 Gland, 242, 296, 330, 336, 356, 359, 364, 367, 370, 374, 375, 378 Glomerular, 330, 368 Glomeruli, 330 Glomerulonephritis, 174, 178, 225, 330 Glomerulus, 330, 351 Glucocorticoid, 32, 330 Glucose Intolerance, 58, 198, 199, 320, 330 Glucose tolerance, 4, 5, 43, 44, 111, 118, 179, 331 Glucose Tolerance Test, 5, 43, 44, 179, 331 Glutamic Acid, 328, 331, 363 Glutathione Peroxidase, 331, 371 Glycerol, 331, 359 Glycerophospholipids, 331, 359 Glycine, 212, 306, 320, 331, 371 Glycodeoxycholic Acid, 195, 331 Glycogen, 205, 227, 331, 359 Glycols, 331, 336 Glycoprotein, 46, 108, 115, 224, 328, 331, 342, 377, 380 Glycosaminoglycan, 36, 56, 331 Glycosidic, 331, 359 Glycosylation, 192, 223, 331 Gonad, 331 Gonadal, 31, 331, 374 Gonadorelin, 332, 343 Gonadotropin, 198, 332, 343 Governing Board, 332, 362 Grade, 9, 74, 96, 332 Grading, 17, 332 Graft, 6, 162, 166, 187, 332, 335, 350 Grafting, 4, 76, 96, 187, 317, 332 Gram-negative, 325, 332 Gram-Negative Bacteria, 325, 332 Granule, 212, 332, 369 Granulocytes, 332, 350, 372, 383 Granuloma, 281, 332 Granuloma Annulare, 281, 332 Grasses, 328, 332 Gravis, 234, 332 Growth factors, 54, 62, 175, 203, 219, 238, 332 Guanylate Cyclase, 232, 233, 332, 353 H Habitual, 8, 312, 332 Half-Life, 185, 333 Haplotypes, 14, 333 Haptens, 296, 333 Headache, 308, 333, 337, 339
Health Care Costs, 19, 333 Health Expenditures, 333 Health Promotion, 12, 333 Heart attack, 5, 7, 12, 152, 164, 183, 189, 193, 197, 209, 210, 216, 217, 220, 279, 309, 333 Heart failure, 52, 103, 178, 208, 219, 224, 233, 299, 333 Heartbeat, 333, 375 Heartburn, 241, 333, 338 Helix-loop-helix, 37, 333 Heme, 48, 233, 306, 318, 333, 356, 362 Hemodialysis, 82, 84, 102, 113, 119, 320, 333, 342 Hemodynamics, 241, 333 Hemoglobin, 33, 299, 326, 333 Hemorheology, 239, 334 Hemorrhage, 323, 333, 334, 350, 375, 382 Hemostasis, 58, 82, 178, 224, 334, 371 Heparin, 334, 360 Hepatic, 34, 36, 41, 65, 66, 74, 111, 118, 238, 297, 319, 331, 334, 349, 358, 362, 372 Hepatitis, 186, 223, 224, 259, 334 Hepatitis A, 224, 334 Hepatocyte, 66, 334 Hepatovirus, 334 Hereditary, 187, 226, 315, 334, 349, 352 Heredity, 329, 330, 334 Heterodimer, 18, 233, 334 Heterogeneity, 41, 296, 334 High blood cholesterol, 187, 226, 278, 279, 334 High-density lipoproteins, 86, 334 Hip Fractures, 177, 327, 335 Hippocampus, 335, 352 Hirsutism, 14, 177, 318, 335, 336, 337 Histamine, 299, 335, 337 Histidine, 212, 233, 335 Histology, 71, 335, 352 Homeopathic remedies, 238, 335 Homeostasis, 65, 96, 179, 186, 201, 230, 246, 335, 373 Homicide, 159, 335 Homogeneous, 35, 195, 303, 335, 358 Homologous, 216, 233, 297, 330, 335, 376 Hormonal, 11, 198, 304, 326, 335, 347 Hormone Replacement Therapy, 89, 99, 108, 115, 130, 164, 165, 166, 177, 335 Hormone therapy, 92, 134, 164, 335 Host, 17, 53, 58, 208, 229, 305, 335, 338, 343, 349, 381, 382 Humoral, 63, 68, 252, 335
Index 393
Humour, 335 Hybrid, 313, 335 Hybridomas, 335, 340 Hydrogen, 295, 305, 308, 309, 310, 319, 327, 331, 336, 343, 349, 352, 355, 358, 365, 375 Hydrogen Peroxide, 310, 331, 336, 343, 375 Hydrolysis, 38, 69, 302, 336, 341, 359, 361, 365 Hydrophobic, 320, 331, 336, 343 Hydroxides, 336 Hydroxyl Radical, 233, 336 Hydroxylysine, 314, 336 Hydroxyproline, 314, 336 Hygienic, 336, 372 Hyperaemia, 315, 336 Hyperandrogenism, 14, 336 Hyperbaric, 239, 336 Hyperbaric oxygen, 239, 336 Hyperglycaemia, 113, 120, 336 Hyperglycemia, 37, 74, 179, 198, 199, 200, 202, 205, 221, 222, 227, 240, 242, 336 Hyperhomocysteinemia, 102, 130, 157, 318, 336 Hyperlipoproteinemia, 336, 337 Hypersensitivity, 73, 229, 297, 336, 343, 369 Hypersensitivity, Immediate, 297, 336 Hypertrichosis, 335, 337 Hypertriglyceridemia, 12, 179, 222, 225, 322, 337 Hypertrophy, 13, 201, 208, 219, 316, 337, 379 Hyperuricemia, 200, 337 Hypobetalipoproteinemia, 192, 337 Hypoglycaemia, 319, 337 Hypoglycemia, 205, 228, 238, 240, 241, 337 Hypoglycemic, 202, 205, 228, 337 Hypoglycemic Agents, 202, 205, 228, 337 Hypogonadism, 176, 337 Hypolipidemic, 63, 337 Hypotension, 219, 316, 337 Hypothalamic, 31, 337 Hypothalamus, 304, 307, 317, 321, 332, 337, 360 Hypoxia, 319, 337 Hysterectomy, 164, 337 I Id, 122, 135, 193, 281, 288, 290, 337 Ileal, 181, 182, 207, 251, 337 Ileum, 337, 383
Iliac Artery, 327, 337 Imaging procedures, 337, 378 Imidazole, 221, 335, 338 Immersion, 305, 338 Immune Sera, 338 Immunity, 42, 76, 77, 93, 103, 234, 252, 297, 338, 345, 354, 379 Immunization, 68, 338 Immunodeficiency, 219, 338 Immunogenic, 338, 343 Immunoglobulin, 300, 338, 349 Immunohistochemistry, 30, 338 Immunologic, 51, 312, 338, 345, 367 Immunology, 23, 79, 221, 241, 296, 338 Immunosuppressive, 330, 338 Impairment, 16, 44, 64, 69, 319, 322, 327, 338, 347 Implant radiation, 338, 340, 341, 366, 383 Impotence, 137, 241, 253, 281, 326, 338 In situ, 223, 338 In vitro, 15, 21, 22, 26, 29, 36, 41, 46, 47, 52, 59, 60, 62, 65, 190, 338, 361, 378 Incision, 338, 340 Incubation, 131, 192, 338 Indicative, 190, 242, 338, 357, 381 Indigestion, 241, 338 Indinavir, 41, 338 Induction, 16, 39, 49, 54, 73, 175, 186, 215, 220, 224, 299, 338, 372, 382 Infancy, 240, 339 Inferior vena cava, 71, 339 Infertility, 14, 241, 339 Infiltration, 59, 211, 330, 339 Inflammatory bowel disease, 174, 180, 201, 212, 339 Influenza, 45, 240, 339 Infusion, 211, 339, 350 Ingestion, 331, 339, 361, 377 Initiation, 13, 26, 30, 37, 38, 39, 50, 51, 54, 59, 64, 70, 82, 339, 363, 379 Inorganic, 296, 336, 339 Inotropic, 303, 339 Inpatients, 47, 339 Insecticides, 339, 358 Insight, 5, 15, 29, 46, 58, 61, 71, 230, 339 Insulator, 339, 350 Insulin-dependent diabetes mellitus, 179, 340 Insulin-like, 176, 340 Intercellular Adhesion Molecule-1, 174, 340 Interleukin-1, 28, 340
394 Atherosclerosis
Interleukin-2, 340 Interleukin-6, 34, 67, 81, 340 Intermediate Filaments, 340, 352 Intermittent, 137, 155, 221, 241, 340 Internal Medicine, 6, 19, 30, 34, 36, 58, 85, 100, 113, 120, 134, 324, 340 Internal radiation, 340, 341, 366, 383 Interstitial, 307, 327, 340, 341, 351, 368, 383 Intervention Studies, 158, 340 Intestinal, 65, 182, 184, 192, 310, 320, 331, 340 Intestine, 193, 306, 307, 325, 340, 342 Intoxication, 319, 340, 383 Intracellular, 47, 188, 196, 219, 226, 232, 308, 339, 340, 353, 362, 364, 371, 372 Intravenous, 5, 43, 44, 339, 340 Intrinsic, 296, 305, 340 Invasive, 4, 70, 112, 119, 153, 186, 249, 338, 340, 345 Involuntary, 305, 341, 351, 367, 373 Ion Channels, 233, 341, 352, 376 Ion Transport, 341, 348 Ions, 305, 308, 312, 321, 323, 336, 341, 349, 365 Irradiation, 240, 341, 383 Ischemic stroke, 82, 341 Islet, 238, 341 Isoflavones, 67, 110, 117, 130, 132, 341 Isopropyl, 183, 184, 341 Isozymes, 47, 341 J Joint, 23, 36, 176, 303, 341, 355, 376 K Kallidin, 307, 341 Kb, 270, 341 Keratolytic, 319, 341, 361 Ketone Bodies, 320, 341, 342 Ketosis, 320, 342 Kidney Disease, 171, 238, 240, 241, 242, 260, 270, 280, 295, 342 Kidney Failure, 325, 342 Kidney Transplantation, 5, 342 Kinetics, 29, 42, 71, 342 L Labile, 185, 314, 342 Lactation, 342, 356 Lag, 28, 342 Laminin, 305, 327, 342 Large Intestine, 321, 340, 342, 367, 372 Latent, 248, 342, 363 Laxative, 297, 342, 373 Lens, 310, 342, 382
Leprosy, 329, 342 Leptin, 104, 342 Lethal, 304, 342 Leukocytes, 52, 58, 174, 180, 211, 212, 216, 217, 223, 224, 305, 307, 312, 325, 332, 342, 349, 380 Leukotrienes, 302, 323, 343, 344 Leuprolide, 198, 343 Libido, 176, 299, 343 Library Services, 288, 343 Ligament, 343, 364 Ligands, 46, 191, 219, 230, 310, 343, 375 Linkage, 43, 44, 160, 343, 359 Linkage Disequilibrium, 43, 44, 343 Lipase, 36, 65, 69, 74, 77, 111, 118, 343 Lipid A, 20, 59, 66, 71, 162, 175, 192, 212, 214, 228, 343 Lipid Peroxidation, 28, 39, 52, 54, 69, 193, 343, 356 Lipid Peroxides, 193, 343 Lipopolysaccharide, 28, 53, 212, 215, 332, 343 Lipoprotein(a), 134, 343 Lipoxygenase, 20, 37, 45, 48, 52, 63, 113, 120, 302, 343, 344 Lipoxygenase Inhibitors, 20, 344 Liver scan, 344, 370 Liver Transplantation, 152, 344 Localization, 25, 31, 38, 42, 54, 55, 76, 108, 115, 338, 344 Localized, 17, 38, 57, 298, 319, 332, 335, 337, 339, 342, 344, 349, 360, 380 Longitudinal Studies, 184, 344 Longitudinal study, 90, 176, 344 Loop, 143, 188, 344 Lovastatin, 206, 218, 344, 372 Lumbar, 177, 344 Lumen, 11, 26, 163, 182, 197, 211, 216, 235, 325, 344 Lupus, 10, 24, 138, 151, 152, 153, 154, 174, 224, 234, 261, 280, 300, 301, 344, 376 Lycopene, 112, 118, 143, 156, 344 Lymph, 304, 313, 324, 335, 345, 375 Lymphatic, 324, 339, 345, 347, 373, 374, 378 Lymphocyte, 20, 42, 61, 301, 345, 346, 349 Lymphoid, 26, 300, 317, 345 Lymphokines, 345 Lysine, 28, 181, 192, 336, 345 Lysophospholipids, 54, 345 Lytic, 345, 371
Index 395
M Macrophage Activation, 252, 345 Macula, 345 Macula Lutea, 345 Macular Degeneration, 137, 159, 195, 196, 203, 345 Magnetic Resonance Angiography, 153, 163, 345 Magnetic Resonance Imaging, 160, 163, 167, 345, 370 Major Histocompatibility Complex, 333, 345 Malignancy, 295, 345 Malignant, 22, 234, 301, 303, 345, 351, 355, 366 Malnutrition, 91, 241, 297, 303, 308, 345 Mammary, 68, 317, 346, 367 Mammogram, 308, 346, 347 Mandible, 298, 312, 346, 368 Mania, 346 Manic, 219, 346 Manifest, 33, 101, 210, 212, 346 Matrix metalloproteinase, 54, 91, 94, 346 Meat, 321, 346, 370 Medial, 4, 9, 15, 18, 25, 28, 32, 41, 156, 210, 303, 346 Mediate, 26, 41, 46, 56, 65, 193, 219, 222, 230, 310, 346 Mediator, 13, 64, 69, 219, 340, 346, 360, 371 MEDLINE, 271, 346 Medroxyprogesterone, 34, 177, 346 Medroxyprogesterone Acetate, 34, 177, 346 Megaloblastic, 328, 346 Melanin, 346, 359, 380 Melanosis, 295, 346 Memory, 300, 319, 346 Meninges, 311, 346 Menopause, 67, 137, 159, 165, 176, 241, 346, 357, 362, 363, 364 Menstrual Cycle, 346, 363 Menstruation, 298, 346, 354 Mental Disorders, 171, 347 Mental Health, iv, 13, 171, 270, 272, 347, 365 Mental Retardation, 219, 347 Mesenchymal, 325, 347 Mesenteric, 201, 347 Mesentery, 347, 358 Mesoderm, 193, 347 Meta-Analysis, 94, 347 Metabolic disorder, 198, 199, 320, 347
Metabolite, 321, 344, 347, 362, 363 Metastasis, 180, 191, 203, 310, 346, 347 Methionine, 129, 143, 321, 347, 375 Methyltestosterone, 177, 347 Metoprolol, 213, 347 MI, 96, 160, 184, 188, 199, 227, 278, 279, 293, 347 Microbe, 347, 378 Microbiology, 79, 90, 111, 117, 304, 347 Microcalcifications, 308, 347 Microcirculation, 31, 45, 86, 242, 347, 360 Microdialysis, 32, 348 Micronutrients, 28, 348 Microorganism, 313, 348, 356, 382 Micro-organism, 319, 348 Microscopy, 57, 305, 348 Microtubule-Associated Proteins, 348, 352 Microtubules, 340, 348, 352 Midaxillary line, 348, 383 Migration, 26, 37, 46, 59, 62, 183, 203, 224, 235, 340, 345, 348 Milligram, 7, 240, 348 Milliliter, 307, 348 Millimeter, 348, 383 Mineralization, 21, 348 Mineralocorticoids, 242, 296, 348 Minority Groups, 9, 348 Mitochondria, 27, 213, 222, 348, 350 Mitochondrial Swelling, 348, 351 Mitosis, 302, 348 Mitotic, 326, 348 Modeling, 71, 222, 348 Modification, 11, 12, 18, 23, 33, 61, 63, 76, 87, 90, 96, 114, 120, 175, 222, 330, 349, 366 Modulator, 220, 349 Molecular Structure, 349, 379 Monitor, 24, 240, 317, 349, 353 Monoamine, 349, 380 Monoamine Oxidase, 349, 380 Monoclonal, 175, 335, 341, 349, 366, 383 Monocyte, 16, 23, 26, 28, 37, 41, 45, 49, 55, 58, 59, 70, 109, 116, 132, 212, 213, 349 Monocyte Chemoattractant Protein-1, 109, 116, 349 Mononuclear, 23, 57, 175, 332, 349, 380 Monophosphate, 232, 349 Monounsaturated fat, 73, 129, 349 Morphological, 46, 63, 323, 349 Morphology, 23, 57, 250, 345, 349 Movement Disorders, 349 Mucins, 320, 349
396 Atherosclerosis
Mucosa, 344, 349, 375 Multicenter study, 7, 157, 349 Multiple sclerosis, 174, 180, 234, 350 Muscular Dystrophies, 322, 350 Mutagenesis, 46, 70, 350 Mutagens, 329, 350 Myalgia, 339, 350 Myasthenia, 234, 350 Mydriatic, 321, 350 Myelin, 350 Myeloid Cells, 47, 350 Myelosuppression, 219, 350 Myocardial infarction, 5, 13, 28, 33, 40, 51, 52, 69, 76, 90, 94, 98, 99, 161, 174, 178, 197, 208, 216, 219, 225, 317, 347, 350, 364 Myocardial Ischemia, 162, 166, 167, 168, 180, 202, 205, 227, 299, 317, 350 Myocardial Reperfusion, 350, 368 Myocardial Reperfusion Injury, 350, 368 Myocarditis, 280, 350 Myocardium, 299, 347, 350, 351 Myosin, 351, 379 N Narcotic, 351, 353 Nasal Mucosa, 339, 351 Natriuresis, 299, 351 Natural selection, 306, 351 Nausea, 322, 338, 342, 351, 380, 381 NCI, 1, 170, 269, 313, 351 Necrobiosis Lipoidica, 281, 351 Necrosis, 186, 195, 212, 302, 308, 311, 339, 347, 350, 351, 368 Neocortex, 351, 352 Neoplasm, 351, 380 Nephritis, 186, 223, 351 Nephropathy, 179, 191, 202, 205, 206, 223, 238, 241, 242, 342, 351 Nephrosis, 351 Nephrotic, 190, 351 Nephrotic Syndrome, 190, 351 Nervous System, 31, 55, 234, 280, 295, 296, 297, 304, 305, 307, 308, 311, 329, 331, 333, 343, 346, 350, 351, 352, 354, 357, 371, 376, 380 Neural, 195, 296, 298, 335, 349, 351 Neuralgia, 241, 352 Neurodegenerative Diseases, 195, 199, 223, 305, 352 Neuroendocrine, 30, 352 Neuroendocrinology, 241, 352 Neurofibrillary Tangles, 223, 352 Neurofilaments, 352
Neurogenic, 352, 381 Neurologic, 229, 352 Neuronal, 27, 178, 195, 212, 225, 352 Neurons, 27, 178, 185, 192, 225, 319, 329, 351, 352, 353, 376 Neuropathy, 7, 179, 202, 205, 206, 239, 241, 242, 254, 304, 352, 358 Neuropeptide, 317, 352 Neurotransmitters, 349, 352, 373 Neutrons, 297, 341, 352, 366 Neutropenia, 219, 352 Neutrophil, 340, 353 Niacin, 128, 162, 353, 379 Nicotine, 254, 353 Nisoldipine, 95, 353 Nitric Oxide, 16, 31, 44, 51, 62, 64, 69, 72, 162, 169, 185, 227, 242, 247, 353 Nitrogen, 30, 176, 233, 297, 299, 327, 353, 379 Nitroglycerin, 185, 353 Nitrous Oxide, 253, 353 Norepinephrine, 296, 353 Norethindrone, 177, 353 Normotensive, 41, 88, 190, 353 Nuclear, 30, 45, 48, 50, 111, 118, 177, 196, 201, 258, 305, 315, 323, 326, 329, 351, 353, 377 Nuclear Proteins, 196, 353 Nuclei, 196, 297, 315, 323, 330, 345, 348, 352, 354, 365 Nucleic acid, 23, 208, 215, 223, 330, 350, 353, 354, 366 Nucleoproteins, 354 Nucleus, 32, 188, 198, 302, 305, 312, 317, 318, 325, 326, 340, 349, 352, 353, 354, 365, 373, 374 O Observational study, 15, 158, 162, 354 Ocular, 57, 203, 354 Odds Ratio, 7, 10, 354, 367 Ointments, 322, 354, 372 Oligomenorrhea, 354, 361 Omega-3 fatty acid, 130, 132, 161, 354 Opacity, 310, 319, 354 Operon, 354, 363 Ophthalmic, 354, 369 Opsin, 354, 368 Optic Disk, 316, 320, 345, 354 Optic Nerve, 354, 368, 369 Organ Culture, 355, 378 Ornithine, 16, 355 Osmotic, 297, 348, 355, 371
Index 397
Osteoarthritis, 195, 196, 212, 219, 239, 355 Osteoblasts, 21, 355 Osteogenic sarcoma, 355 Osteonecrosis, 280, 355 Osteoporosis, 21, 45, 84, 137, 176, 178, 195, 196, 219, 225, 240, 326, 355, 367 Osteosarcoma, 178, 225, 355 Ovariectomy, 68, 355 Ovaries, 14, 302, 336, 355, 361, 371 Ovary, 258, 317, 326, 331, 355, 361, 375 Overexpress, 29, 49, 355 Overweight, 12, 121, 292, 355 Ovulation, 203, 300, 353, 355 Ovum, 317, 330, 355, 363, 383 Oxidants, 108, 112, 115, 119, 158, 355 Oxidation-Reduction, 355 Oxidative Stress, 15, 20, 31, 35, 37, 39, 55, 64, 69, 128, 134, 156, 162, 217, 227, 356 Oxides, 20, 356 Oxygenase, 48, 356 Oxytocin, 31, 356 P Palliative, 318, 356, 377 Pancreas, 5, 193, 238, 254, 295, 306, 321, 340, 341, 343, 356, 380 Pancreas Transplant, 238, 356 Pancreas Transplantation, 238, 356 Pancreatic, 69, 176, 310, 356 Pancreatic cancer, 176, 356 Pancreatitis, 223, 224, 280, 356 Parathyroid, 98, 242, 356, 377 Parathyroid Glands, 356 Parathyroid hormone, 98, 356 Paroxysmal, 299, 356 Particle, 38, 100, 356, 373, 379 Pathogen, 17, 53, 60, 338, 356 Pathologic, 51, 78, 295, 302, 306, 307, 316, 336, 357, 365, 368 Pathologic Processes, 302, 357 Pathologies, 187, 222, 234, 357 Pathophysiology, 4, 57, 59, 242, 252, 357 Patient Care Team, 280, 357 Patient Education, 239, 253, 278, 281, 286, 288, 293, 357 Pelvic, 324, 357, 364 Penicillin, 300, 357, 381 Peptide, 16, 21, 45, 178, 186, 224, 225, 233, 234, 324, 342, 357, 361, 364, 365 Perception, 213, 315, 357 Percutaneous, 4, 216, 357 Perennial, 357, 379 Perfusion, 235, 337, 357
Pericarditis, 137, 280, 357 Pericardium, 357, 376 Perimenopausal, 176, 357 Perinatal, 203, 357 Periodontal disease, 12, 50, 52, 54, 100, 176, 229, 298, 357 Periodontitis, 12, 17, 50, 53, 92, 229, 357 Perioperative, 239, 241, 242, 357 Peripheral blood, 55, 58, 357 Peripheral Nervous System, 352, 357, 375 Peripheral Neuropathy, 254, 358 Peritoneal, 41, 358 Peritoneum, 347, 358 Peroxide, 62, 358 Peroxisome Proliferators, 230, 358 Pesticides, 240, 339, 358 PH, 83, 103, 307, 358 Phagocyte, 23, 57, 355, 358 Pharmaceutical Preparations, 232, 326, 329, 358 Pharmaceutical Solutions, 322, 358 Pharmacologic, 5, 49, 66, 281, 299, 333, 358, 378, 381 Pharmacotherapy, 227, 241, 358 Pharynx, 339, 358 Phenotype, 19, 24, 26, 42, 68, 358 Phenyl, 174, 358 Phenylalanine, 359, 380 Phlebotomy, 162, 359 Phosphatidic Acids, 345, 359 Phospholipases, 359, 372 Phospholipids, 20, 37, 45, 54, 55, 66, 221, 231, 300, 301, 327, 343, 359 Phosphorus, 308, 356, 359 Phosphorylase, 205, 227, 359 Phosphorylate, 222, 359 Phosphorylated, 51, 313, 359 Phosphorylation, 50, 51, 196, 219, 222, 296, 317, 359 Photocoagulation, 313, 359 Photoreceptor, 57, 359 Physical Examination, 163, 167, 334, 359 Physiologic, 5, 31, 35, 51, 58, 63, 297, 306, 327, 333, 346, 348, 359, 364, 367, 368 Physiology, 31, 40, 43, 44, 57, 111, 113, 118, 119, 182, 241, 250, 253, 256, 309, 324, 359 Pigment, 306, 344, 359 Pilot study, 29, 359 Pituitary Gland, 241, 317, 332, 359 Placenta, 302, 326, 360, 363
398 Atherosclerosis
Plants, 297, 313, 330, 349, 353, 360, 361, 362, 369, 370, 378, 379 Plasma cells, 300, 360 Plasma protein, 203, 297, 324, 360, 365, 371 Plasma Volume, 348, 360 Plasmin, 360 Plasminogen, 4, 33, 40, 76, 99, 360 Plasminogen Activator Inhibitor 1, 4, 360 Plasminogen Activators, 360 Platelet Activation, 28, 131, 233, 258, 360, 372 Platelet Aggregation, 64, 178, 202, 225, 259, 299, 353, 360, 377 Platelet Factor 4, 28, 360 Platelets, 28, 53, 56, 85, 190, 211, 234, 249, 251, 260, 302, 350, 353, 360, 361, 377 Platinum, 344, 361 Podiatrist, 239, 361 Podophyllotoxin, 326, 361 Poisoning, 308, 319, 340, 351, 361 Pollen, 361, 366 Polycystic, 14, 154, 221, 258, 336, 361 Polycystic Ovary Syndrome, 154, 221, 336, 361 Polydipsia, 254, 361 Polymerase, 54, 90, 195, 361, 363 Polymerase Chain Reaction, 54, 90, 361 Polymers, 194, 361, 362, 365 Polymorphic, 70, 86, 361 Polymorphism, 20, 69, 70, 82, 89, 160, 361 Polypeptide, 20, 192, 208, 219, 220, 298, 313, 325, 328, 360, 361, 364, 383 Polyphagia, 254, 362 Polyphosphates, 229, 362 Polysaccharide, 301, 331, 362, 365 Polyuria, 254, 362 Porphyria, 359, 362 Porphyria Cutanea Tarda, 359, 362 Posterior, 298, 303, 311, 312, 348, 356, 362 Postnatal, 114, 120, 362, 374 Postoperative, 81, 362 Postprandial, 79, 168, 362 Postsynaptic, 362, 372, 376 Post-translational, 222, 362 Potassium, 348, 362, 372 Potentiates, 340, 362 Potentiation, 362, 372 Practice Guidelines, 272, 362 Pravastatin, 190, 206, 362 Precipitation, 234, 363 Precursor, 16, 44, 225, 226, 299, 302, 323, 325, 353, 359, 360, 363, 365, 379, 380, 381
Predisposition, 187, 209, 226, 234, 363 Preeclampsia, 190, 191, 363 Premenopausal, 24, 83, 88, 133, 363 Pressoreceptors, 305, 363 Prevalence, 9, 10, 13, 35, 55, 71, 91, 98, 159, 160, 161, 242, 261, 354, 363 Primary endpoint, 11, 363 Probe, 45, 58, 109, 116, 164, 348, 363 Prodrug, 184, 205, 206, 363 Progesterone, 143, 164, 166, 353, 363, 374 Progressive disease, 214, 363 Projection, 319, 353, 354, 363 Proline, 70, 314, 336, 363 Promoter, 45, 89, 99, 111, 118, 177, 363 Promotor, 210, 363, 368 Prone, 17, 47, 61, 68, 71, 148, 168, 363 Prophylaxis, 181, 182, 187, 207, 221, 223, 232, 320, 363, 381 Proportional, 363, 375 Propranolol, 303, 364 Prospective study, 344, 364 Prostaglandin, 213, 299, 364, 377 Prostaglandins A, 7, 364 Prostaglandins D, 364 Prostate, 176, 306, 364, 380 Protease, 40, 49, 74, 90, 170, 178, 212, 224, 259, 314, 338, 364, 369 Protease Inhibitors, 40, 74, 90, 170, 259, 364 Protein C, 63, 67, 68, 153, 178, 180, 214, 224, 297, 298, 301, 305, 327, 343, 364, 379, 381 Protein Conformation, 298, 364 Protein Kinases, 199, 231, 233, 365 Protein S, 188, 196, 219, 250, 306, 330, 364, 365, 369 Proteins, 15, 17, 20, 22, 25, 46, 48, 52, 55, 57, 62, 70, 97, 109, 111, 116, 118, 181, 187, 188, 189, 192, 199, 203, 204, 212, 216, 222, 230, 232, 233, 246, 298, 301, 307, 310, 311, 312, 314, 327, 328, 331, 334, 340, 346, 348, 349, 352, 353, 354, 357, 360, 361, 364, 365, 367, 371, 377, 378 Proteinuria, 351, 363, 365 Proteoglycan, 29, 36, 71, 360, 365 Proteolytic, 25, 178, 225, 298, 314, 328, 360, 365 Prothrombin, 365, 377 Protocol, 11, 18, 53, 161, 365 Protons, 297, 336, 365, 366 Proximal, 28, 92, 129, 322, 365 Pruritic, 323, 365
Index 399
Psoriasis, 174, 188, 203, 204, 208, 219, 223, 365 Psychic, 343, 365, 370 Psychogenic, 365, 381 Psychomotor, 309, 319, 365 Psychoneuroimmunology, 29, 365 Puberty, 176, 365 Public Health, 8, 18, 51, 112, 118, 242, 252, 272, 365 Public Policy, 271, 365 Publishing, 4, 72, 239, 366 Pulmonary, 31, 71, 137, 138, 224, 307, 316, 342, 343, 366, 382 Pulmonary Artery, 71, 307, 366, 382 Pulmonary hypertension, 71, 316, 366 Pulse, 93, 292, 349, 366 Pupil, 316, 321, 350, 366 Purines, 366, 371 Putrefaction, 329, 366 Pyrogenic, 216, 366 Q Quality of Life, 83, 366 Quaternary, 49, 364, 366 Quercetin, 124, 202, 366 R Race, 160, 348, 366 Radiation, 153, 299, 304, 327, 328, 336, 340, 341, 345, 366, 370, 372, 383 Radiation therapy, 327, 336, 340, 341, 366, 383 Radioactive, 153, 304, 307, 333, 336, 338, 340, 341, 344, 353, 366, 370, 383 Radioisotope, 366, 378 Radiolabeled, 57, 109, 114, 116, 121, 341, 366, 383 Radiological, 357, 366 Radiotherapy, 307, 341, 366, 383 Raloxifene, 367, 371 Randomized, 28, 84, 93, 100, 130, 157, 323, 367 Reabsorption, 325, 367 Reactive Oxygen Species, 27, 31, 55, 217, 224, 367 Reagent, 186, 225, 367 Recombinant, 29, 184, 186, 219, 225, 367, 381 Recombination, 315, 330, 367 Rectum, 307, 321, 328, 329, 339, 342, 364, 367 Red blood cells, 326, 350, 356, 362, 367, 370
Reductase, 28, 69, 82, 181, 184, 190, 206, 218, 222, 302, 344, 362, 367, 372 Refer, 1, 297, 308, 314, 344, 345, 352, 367 Reflex, 27, 367 Refraction, 367, 374 Regeneration, 189, 367 Regimen, 323, 358, 367 Regurgitation, 333, 367 Relative risk, 160, 367 Renal failure, 5, 57, 195, 196, 254, 319, 368 Renin, 242, 299, 309, 368 Renin-Angiotensin System, 242, 299, 309, 368 Reperfusion, 174, 195, 208, 209, 215, 350, 368 Reperfusion Injury, 174, 195, 215, 368 Resorption, 298, 367, 368 Respiration, 328, 349, 368 Respiratory distress syndrome, 223, 368 Response Elements, 177, 368 Restoration, 350, 368, 375, 383 Resuscitation, 323, 368 Retina, 57, 181, 312, 316, 320, 342, 345, 354, 368, 369, 382 Retinal, 57, 94, 159, 195, 196, 315, 320, 321, 354, 368, 369 Retinal Vein, 94, 369 Retinal Vein Occlusion, 94, 369 Retinoid, 76, 230, 369 Retinol, 368, 369 Retinopathy, 179, 191, 206, 223, 242, 320, 369 Reversion, 369, 380 Rheumatism, 81, 223, 369 Rheumatoid, 10, 22, 55, 81, 154, 155, 180, 181, 208, 212, 219, 230, 234, 238, 355, 369 Rheumatoid arthritis, 10, 22, 55, 81, 155, 180, 181, 208, 212, 219, 230, 234, 238, 369 Rhinitis, 174, 369 Ribose, 30, 195, 295, 369 Ribosome, 369, 379 Ritonavir, 41, 369 Rod, 359, 369 Rodenticides, 358, 369 Rosiglitazone, 4, 202, 205, 369 Rutin, 202, 366, 369 S Salivary, 318, 320, 321, 356, 369, 375 Salivary glands, 318, 320, 321, 369 Saphenous, 71, 317, 370 Saphenous Vein, 71, 317, 370 Saponins, 370, 374
400 Atherosclerosis
Saturate, 43, 44, 370 Saturated fat, 9, 33, 73, 129, 370 Scans, 18, 70, 161, 370 Schematic, 195, 370 Schizophrenia, 219, 370, 383 Sclerosis, 71, 281, 303, 350, 370 Screening, 48, 70, 101, 158, 162, 186, 225, 313, 370 Scrotum, 370, 376 Sebaceous, 370, 382 Sebaceous gland, 370, 382 Secondary tumor, 347, 370 Secretion, 8, 176, 197, 213, 238, 325, 332, 335, 336, 340, 342, 348, 349, 370, 371, 381, 382 Secretory, 38, 48, 370, 376 Sedentary, 10, 32, 370 Seizures, 309, 319, 356, 370 Selective estrogen receptor modulator, 68, 367, 371 Selenium, 113, 120, 124, 133, 156, 371 Sella, 359, 371 Semen, 364, 371 Semisynthetic, 326, 371 Senescence, 195, 371 Senile, 355, 371 Sensor, 164, 167, 371 Sepsis, 223, 371 Septic, 195, 196, 214, 219, 371 Sequencing, 361, 371 Serine, 49, 51, 66, 178, 199, 212, 219, 224, 318, 324, 371 Serologic, 32, 371 Serotonin, 349, 358, 371, 379 Serous, 324, 371 Serum Albumin, 7, 371 Sex Characteristics, 299, 365, 371, 377 Sexually Transmitted Diseases, 240, 371 Shock, 92, 97, 108, 111, 115, 118, 195, 196, 214, 219, 371, 379 Side effect, 177, 205, 228, 239, 254, 263, 296, 306, 337, 350, 372, 378 Signal Transduction, 50, 56, 70, 178, 188, 196, 219, 225, 235, 372 Signs and Symptoms, 158, 372, 380 Simvastatin, 89, 206, 218, 372 Skeletal, 195, 222, 299, 350, 372, 373, 379 Skeleton, 295, 327, 341, 364, 372 Skin Aging, 195, 196, 372 Skin Care, 280, 372 Skull, 372, 376
Small intestine, 306, 313, 322, 335, 337, 340, 372 Soaps, 281, 372 Social Behavior, 31, 372 Social Conditions, 31, 373 Social Environment, 32, 366, 373 Social Support, 29, 373 Sodium, 184, 241, 331, 348, 351, 367, 372, 373 Soft tissue, 58, 307, 372, 373 Solid tumor, 299, 373 Solitary Nucleus, 304, 373 Solvent, 305, 326, 331, 355, 358, 373 Somatic, 335, 348, 357, 358, 373 Sorbitol, 205, 206, 373 Sound wave, 170, 373, 380 Spasm, 228, 373, 377 Specialist, 282, 321, 373 Specificity, 68, 296, 302, 324, 373 Spectrum, 40, 52, 78, 229, 374 Sperm, 299, 312, 361, 374, 376 Spermatogenesis, 176, 374 Spermatozoa, 371, 374 Spinal cord, 307, 308, 311, 312, 346, 351, 352, 357, 367, 374, 376 Spleen, 298, 318, 345, 374 Sporadic, 352, 362, 374 Staging, 239, 370, 374 Stanozolol, 177, 374 Stem Cells, 39, 59, 374 Stent, 4, 374 Sterile, 356, 374 Sterility, 76, 339, 374 Steroid, 65, 187, 224, 226, 230, 302, 306, 317, 334, 370, 372, 374 Stimulant, 233, 308, 335, 341, 374, 381 Stimulus, 24, 58, 180, 316, 322, 341, 342, 367, 374, 377 Stomach, 295, 304, 321, 326, 329, 331, 335, 342, 351, 358, 372, 374 Strand, 196, 361, 374 Stromal, 21, 324, 375 Stromal Cells, 21, 375 Subacute, 339, 375 Subclinical, 14, 15, 33, 81, 91, 100, 104, 148, 149, 154, 157, 158, 159, 258, 260, 339, 370, 375 Subcutaneous, 17, 160, 250, 296, 323, 375, 383 Submaxillary, 325, 375 Subspecies, 373, 375 Substance P, 347, 370, 375
Index 401
Substrate, 196, 215, 222, 310, 325, 344, 375, 380 Subtrochanteric, 335, 375 Suction, 328, 375 Sudden cardiac death, 4, 375 Sulfur, 327, 347, 375 Superoxide, 27, 28, 31, 64, 77, 375 Superoxide Dismutase, 27, 31, 64, 375 Supplementation, 7, 28, 36, 57, 113, 120, 128, 129, 130, 132, 133, 134, 152, 160, 193, 375 Surface Plasmon Resonance, 29, 375 Surgery, Plastic, 239, 375 Sympathetic Nervous System, 30, 31, 299, 304, 376 Sympathomimetic, 325, 353, 376, 380 Symphysis, 312, 364, 376 Symptomatic, 168, 356, 376 Synaptic, 353, 372, 376 Synaptic Transmission, 353, 376 Synergistic, 41, 60, 206, 376 Systemic disease, 234, 376 Systemic lupus erythematosus, 13, 24, 55, 69, 83, 101, 223, 261, 280, 300, 301, 376 Systolic, 10, 32, 337, 376 Systolic blood pressure, 32, 376 Systolic pressure, 10, 376 T Tachycardia, 304, 376 Tachypnea, 304, 376 Taurine, 306, 320, 376 Temporal, 25, 335, 345, 376 Testicles, 197, 370, 376 Testicular, 176, 219, 302, 377 Testis, 326, 377 Testosterone, 77, 89, 177, 197, 258, 367, 377 Tetany, 356, 377 Thalamus, 307, 321, 377 Therapeutics, 48, 108, 111, 115, 118, 184, 265, 349, 377 Thermal, 321, 352, 361, 377 Thigh, 327, 377 Thoracic, 71, 81, 90, 94, 96, 97, 377, 383 Thorax, 295, 344, 377 Threonine, 51, 199, 219, 371, 377 Threshold, 63, 326, 337, 377 Thrombin, 178, 224, 233, 234, 328, 360, 364, 365, 377 Thrombocytes, 361, 377 Thrombolytic, 360, 377 Thrombomodulin, 364, 377 Thrombopenia, 301, 377
Thromboses, 232, 301, 377 Thromboxanes, 302, 323, 377 Thrombus, 215, 252, 317, 339, 341, 350, 360, 377, 382 Thymus, 338, 345, 378 Thyroid, 230, 234, 242, 356, 378, 380 Thyroid Gland, 242, 356, 378 Thyroid Hormones, 378, 380 Thyroxine, 297, 359, 378 Tin, 358, 361, 378 Tissue Culture, 251, 378 Tissue Transplantation, 180, 378 Tolerance, 5, 295, 331, 378 Tomography, 378 Topical, 228, 229, 326, 336, 372, 378 Torsion, 339, 378 Toxaemia, 363, 378 Toxic, iv, 39, 212, 221, 223, 304, 305, 315, 332, 338, 343, 352, 353, 361, 371, 378 Toxicity, 191, 195, 322, 378 Toxicology, 272, 378 Toxins, 194, 229, 301, 339, 378 Trace element, 312, 378 Tracer, 71, 378 Trachea, 358, 378 Transcription Factors, 37, 201, 230, 368, 378 Transduction, 188, 196, 219, 235, 372, 379 Transfection, 306, 379 Transfer Factor, 338, 379 Transferases, 331, 379 Translation, 36, 379 Translational, 47, 379 Transmitter, 253, 295, 341, 346, 353, 379, 380 Transplantation, 5, 59, 88, 102, 134, 174, 195, 238, 313, 338, 345, 379 Trauma, 53, 195, 208, 223, 224, 305, 319, 333, 351, 356, 379 Trees, 25, 379 Triad, 212, 379 Tricuspid Atresia, 316, 379 Tricyclic, 233, 379 Triglyceride, 11, 108, 114, 127, 211, 218, 221, 230, 240, 313, 336, 337, 379 Troglitazone, 202, 205, 379 Tropomyosin, 379 Troponin, 84, 379 Tryptophan, 314, 371, 379 Tuberculosis, 316, 344, 379 Tumor marker, 306, 380 Tumor Necrosis Factor, 213, 224, 380
402 Atherosclerosis
Tumour, 203, 220, 380 Tunica Intima, 324, 380 Type 2 diabetes, 4, 6, 7, 11, 12, 75, 96, 99, 104, 133, 179, 228, 239, 380 Typhimurium, 212, 380 Tyramine, 57, 349, 380 Tyrosine, 47, 188, 196, 231, 232, 380 U Ubiquitin, 22, 352, 380 Ulcer, 239, 319, 380 Ultrasonography, 10, 81, 113, 120, 164, 380 Ultrasound test, 162, 380 Unconscious, 319, 337, 380 Univalent, 336, 355, 380 Uraemia, 356, 380 Urea, 16, 223, 302, 355, 380, 381 Uremia, 342, 368, 381 Urethra, 364, 381 Uric, 337, 366, 381 Urinary, 219, 362, 381 Urinary Retention, 219, 381 Urinate, 381, 382 Urine, 28, 52, 153, 205, 228, 306, 317, 320, 322, 325, 342, 351, 362, 365, 381 Urokinase, 360, 381 Uterine Contraction, 356, 381 Uterus, 164, 176, 317, 324, 337, 347, 355, 363, 381 V Vaccination, 68, 381 Vaccine, 68, 189, 259, 296, 365, 381 Vacuoles, 324, 381 Vagina, 320, 346, 381 Vaginal, 14, 381 Valine, 210, 381 Vascular Resistance, 305, 381 Vasculitis, 241, 356, 381 Vasodilation, 31, 299, 381 Vasodilator, 307, 335, 350, 353, 381 Vasomotor, 68, 176, 326, 381 Vector, 186, 225, 379, 381 Vegetarianism, 240, 382 Vein, 71, 74, 82, 163, 164, 167, 299, 303, 339, 340, 353, 359, 369, 370, 382 Vena, 71, 382 Venous, 80, 184, 259, 301, 303, 308, 310, 311, 353, 365, 379, 382 Venous blood, 308, 311, 382 Venous Thrombosis, 80, 259, 382
Ventral, 193, 337, 382 Ventricle, 301, 303, 316, 335, 337, 366, 376, 377, 379, 382 Ventricular, 13, 31, 51, 70, 73, 88, 113, 119, 316, 350, 379, 382 Ventricular Dysfunction, 51, 382 Venules, 307, 309, 324, 347, 382 Veterinary Medicine, 112, 119, 271, 382 Viral, 174, 186, 212, 215, 216, 219, 328, 339, 379, 382 Virilism, 336, 382 Virilization, 177, 382 Virulence, 17, 304, 378, 382 Virus, 18, 223, 224, 305, 325, 330, 360, 379, 382 Visceral, 43, 158, 200, 304, 358, 382 Visceral Afferents, 304, 382 Vitreous Body, 368, 382 Vitreous Hemorrhage, 320, 382 Vitro, 21, 29, 30, 31, 36, 47, 60, 62, 182, 334, 382 Vivo, 14, 20, 21, 22, 23, 25, 26, 29, 30, 36, 37, 39, 40, 41, 42, 47, 49, 51, 52, 58, 59, 60, 62, 63, 64, 65, 147, 178, 185, 216, 225, 334, 338, 343, 348, 355, 377, 382 Void, 67, 382 W Waist circumference, 96, 383 Wakefulness, 319, 383 War, 9, 383 Weight Gain, 192, 327, 383 White blood cell, 64, 300, 342, 345, 349, 350, 353, 360, 383 Windpipe, 358, 378, 383 Withdrawal, 319, 383 Womb, 381, 383 Wound Healing, 58, 185, 203, 215, 239, 310, 346, 383 X Xanthomatosis, 281, 383 Xenograft, 299, 383 X-ray, 153, 163, 292, 299, 302, 307, 314, 315, 328, 341, 346, 353, 366, 370, 383 X-ray therapy, 341, 383 Y Yeasts, 358, 383 Z Zymogen, 364, 383
Index 403
404 Atherosclerosis
