Lipase - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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

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

R EFERENCES

IPASE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Lipase: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00665-0 1. Lipase-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on lipase. 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 LIPASE ....................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Lipase ............................................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 60 The National Library of Medicine: PubMed ................................................................................ 77 CHAPTER 2. NUTRITION AND LIPASE ........................................................................................... 125 Overview.................................................................................................................................... 125 Finding Nutrition Studies on Lipase ......................................................................................... 125 Federal Resources on Nutrition ................................................................................................. 130 Additional Web Resources ......................................................................................................... 130 CHAPTER 3. ALTERNATIVE MEDICINE AND LIPASE ..................................................................... 133 Overview.................................................................................................................................... 133 National Center for Complementary and Alternative Medicine................................................ 133 Additional Web Resources ......................................................................................................... 158 General References ..................................................................................................................... 161 CHAPTER 4. DISSERTATIONS ON LIPASE ....................................................................................... 163 Overview.................................................................................................................................... 163 Dissertations on Lipase .............................................................................................................. 163 Keeping Current ........................................................................................................................ 165 CHAPTER 5. PATENTS ON LIPASE .................................................................................................. 167 Overview.................................................................................................................................... 167 Patents on Lipase ....................................................................................................................... 167 Patent Applications on Lipase.................................................................................................... 189 Keeping Current ........................................................................................................................ 215 CHAPTER 6. BOOKS ON LIPASE ..................................................................................................... 217 Overview.................................................................................................................................... 217 Chapters on Lipase ..................................................................................................................... 217 CHAPTER 7. MULTIMEDIA ON LIPASE........................................................................................... 221 Overview.................................................................................................................................... 221 Video Recordings ....................................................................................................................... 221 CHAPTER 8. PERIODICALS AND NEWS ON LIPASE........................................................................ 223 Overview.................................................................................................................................... 223 News Services and Press Releases.............................................................................................. 223 Academic Periodicals covering Lipase........................................................................................ 225 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 227 Overview.................................................................................................................................... 227 U.S. Pharmacopeia..................................................................................................................... 227 Commercial Databases ............................................................................................................... 228 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 231 Overview.................................................................................................................................... 231 NIH Guidelines.......................................................................................................................... 231 NIH Databases........................................................................................................................... 233 Other Commercial Databases..................................................................................................... 235 APPENDIX B. PATIENT RESOURCES ............................................................................................... 237 Overview.................................................................................................................................... 237 Patient Guideline Sources.......................................................................................................... 237 Finding Associations.................................................................................................................. 239 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 241 Overview.................................................................................................................................... 241

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Preparation................................................................................................................................. 241 Finding a Local Medical Library................................................................................................ 241 Medical Libraries in the U.S. and Canada ................................................................................. 241 ONLINE GLOSSARIES................................................................................................................ 247 Online Dictionary Directories ................................................................................................... 248 LIPASE DICTIONARY ................................................................................................................. 249 INDEX .............................................................................................................................................. 329

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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 lipase is indexed in search engines, such as www.google.com or others, a nonsystematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about lipase, 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 lipase, 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 lipase. 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 lipase, 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 lipase. 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 LIPASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on lipase.

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

Exercise Training, Without Weight Loss, Increases Insulin Sensitivity and Postheparin Plasma Lipase Activity in Previously Sedentary Adults Source: Diabetes Care. 26(3): 557-562. March 2003. 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 determine the effects of exercise, without weight loss, on insulin sensitivity (S1) postheparin plasma lipase activity (PHPL), intravenous fat clearance rate (K2), and fasting lipids in sedentary adults. Exercise increased S1 and both lipoprotein lipase and hepatic (liver) lipase activities without altering BMI (body mass index), waist circumference, K2, or fasting lipids. Correlations between changes in LPL and the total-to- HDL cholesterol ratio and

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changes in the LPL-to-HL ratio and waist circumference were significant. The authors conclude that exercise, without weight loss, increases S1 and PHPL activity in previously sedentary adults, without changing K2 or fasting lipid levels. Therefore, even modest amounts of exercise in the absence of weight loss positively affect markers of glucose and fat metabolism in previously sedentary, middle-aged adults. 1 figure. 1 table. 26 references.

Federally Funded Research on Lipase The U.S. Government supports a variety of research studies relating to lipase. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to lipase. 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 lipase. The following is typical of the type of information found when searching the CRISP database for lipase: •

Project Title: ALCOHOL AND CHRONIC DISEASE AMONG VULNERABLE POPULATIONS Principal Investigator & Institution: Rimm, Eric B.; Associate Professor; Nutrition; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 01-SEP-1997; Project End 31-MAR-2009 Summary: (provided by applicant): Among healthy populations, the benefits of moderate alcohol consumption are well documented. However, more than 7.5 million Americans are survivors of myocardial infarction (MI) and the epidemic of obesity has given rise to an even larger unhealthy population with dyslipidemia,hypertension, low HDL-C, and hyperglycemia (i.e. metabolic syndrome). The influence that alcohol has on prognosis among these "at risk" groups is crucial for informed decision-making by patients, physicians, and policy-makers. We propose to examine alcohol and chronic disease in vulnerable populations among 121,700 women (32,826 with stored blood samples) in the Nurses' Health Study (1976-2006) and 51,529 men (18,100 with stored blood samples) in the Health Professionals Follow-up Study (1986-2006). First, we will study alcohol intake and risk of mortality among an estimated 3,345 women and 2,835 men with confirmed incident non-fatal MI. Secondly, using blood markers of dyslipidemia and abnormal glucose homeostasis, we will examine alcohol and coronary heart disease (CHD) among participants with metabolic syndrome in a nested case control (1:2) study among the projected 680 women and 534 men who provided blood samples and subsequently developed CHD. Finally, because the purported benefit of

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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alcohol consumption is attributed principally to increased HDL-C, we will examine CHD risk associated with gene-alcohol interactions in genes that modulate HDL-C levels. Specifically, alcohol dehydrogenase-3, hepatic lipase, lipoprotein lipase, cholesteryl ester transport protein, and endothelial lipase. The well characterized large cohorts of women and men with stored blood samples provide an unparalleled opportunity to elucidate the health effects of alcohol among high risk patients. Furthermore, knowledge of populations that may benefit from alcohol (or be at greatest risk) will help in the understanding of the pathophysiology of CHD and aid in the development of more complete clinical guidelines for the growing population of individuals at risk for coronary disease and mortality. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANIMAL ATHEROSCLEROSIS

MODELS

FOR

LIPID

METABOLISM

AND

Principal Investigator & Institution: Chan, Lawrence; Professor of Medicine; Molecular and Cellular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 15-DEC-1993; Project End 30-NOV-2005 Summary: (provided by applicant): The primary objective is to advance our knowledge of lipid metabolism and atherosclerosis using animal models. A major area is the role of 12/15-lipoxygenase (LO) in atherosclerosis. 12/l5LOs are lipid-peroxidizing enzymes that oxygenate polyenoic fatty acids to their corresponding hydroperoxy derivatives. 12/15LOs have proatherogenic properties via their capacity to oxidize LDL, as well as antiatherogenic activities via their predominantly anti-inflammatory action. We previously showed that macrophage-specific 15LO overexpression in rabbits protects against atherosclerosis. In pilot experiments we found that, compared to 12/15LO+/+ apoE-/- mice, 12/15LO-/- apoE-/- mice are protected against atherosclerosis, a finding that is at variance with that of. A major goal of this application is to examine the biochemical milieu associated with 12/15LO expression that may underlie the divergent effects of the enzyme on atherosclerosis. Another major area is the role of intracellular lipolysis in lipid homeostasis. We produced perilipin (plin) knockout mice that displayed constitutional activated lipolysis. Perilipin is a major adipose lipid droplet protein that regulates the activity of hormone-sensitive lipase. Plin-/- mice were lean and resistant to diet-induced obesity. Breeding the plin-/- alleles into ob/ob and db/db mice reversed their obesity phenotype. Interestingly, ruptured atherosclerotic plaques in humans and advanced plaques of apoE-/- mice expressed perilipin. We will investigate the role of 12/15LO and perilipin with 5 specific aims. In the first 2 aims, we will study atherosclerosis development in 12/15LO-/- apoE-/- and 12/15LO+/+ apoE-/- mice, and, identify and quantify the eicosanoids and other metabolites in the atherosclerotic aortas from the 2 genotypes. In aims 3 and 4, to obtain mechanistic insight into the obesity-resistant phenotype of plin-/- mice, we will perform biochemical and molecular characterization as well as in vivo stable isotope and energy expenditure experiments on plin+/+ and plin-/- mice with and without ob/ob or db/db background. The creation of non-obese ob/ob and db/db mice (i.e., those that also inherited the plin-/- alleles) provides a unique opportunity to study the role of leptin in lipid and carbohydrate homeostasis in the presence and absence of obesity. Since perilipin, a lipid dropletassociated protein, is expressed in atherosclerotic lesions, in the last aim and in collaboration with we will compare the atherosclerosis susceptibility and plaque morphology of plin-/- and plin+/+ mice bred into apoE-/- and LDLR-/- background. We believe that the mechanistic experiments proposed will advance our understanding of lipid and carbohydrate metabolism, energy homeostasis, and atherosclerosis.

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

Project Title: ANTHRACYCLINE CARDIOTOXICITY--OXIDATIVE STRESS Principal Investigator & Institution: Sarvazyan, Narine; Associate Professor; Physiology; Texas Tech University Health Scis Center Health Sciences Center Lubbock, Tx 79430 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Doxorubicin and its derivatives are among the most potent anticancer drugs known. Unfortunately their therapeutic efficacy is severely restricted by a doseaccumulated cardiotoxicity. Our preliminary results using adult rat cardiomyocytes as a working model, have shown evidence for the mechanism which could explain how reactive oxygen species generated by doxorubicin provoke myofibrillar degeneration while not causing severe oxidative damage. Specifically, 1) we visualized directly doxorubicin accumulation in cardiac mitochondria and subsequent increase in intracellular oxidation in living cardiomyocytes, 2) observed that doxorubicin administration is associated with redistribution of the protein kinase C epsilon isoform from cytosol to myofibrils, and 3) detected disruption of the periodicity of actin staining after repetitive exposure of myocytes to clinically relevant drug concentrations. Based on these data we propose the following sequence of events: doxorubicin rapidly accumulates in cardiac mitochondria; it then initiates lipid peroxidation via formation of superoxide and drug complexes with transition metals; and although the degree of lipid peroxidation is small and no significant membrane damage occurs, it leads to the activation of phospholipases; lipase thereupon release several second messengers, including arachidonic acid, activating a specific protein kinase C isoform; the kinase then initiates myofibrillar degeneration. To support the above hypothesis we aim to 1) establish a causal relationship between observed doxorubicin-induced kinase translocation and increased free radical formation; 2) to determine whether doxorubicininduced free radicals and/or protein kinase C translocation are prerequisites for changes in myocyte myofibrillar organization and cell contractility; 3) to uncover role of phospholipase A2 in doxorubicin-induced activation of kinase and ensuing changes in myofibrillar organization and contractility. The proposed experiments aim to reveal explicit pathways through which reactive oxygen species are involved in anthracyclineinduced cardiomyopathy. The studies will also provide new information about kinases involvement in myofilament degeneration and interaction between reactive oxygen species and signal transduction pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANTIBODIES TO LIPOPROTEIN LIPASE AND ATHEROSCLEROSIS Principal Investigator & Institution: Reichlin, Morris; Vice President of Research; Oklahoma Medical Research Foundation Oklahoma City, Ok 731045005 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Premature atherosclerosis in patients with Systemic Lupus Erythematosus (SLE) has been recognized for the past 25 years. As much as a 50fold increase in risk for coronary artery disease has been found in SLE patients compared to controls and an increased risk for thrombotic cerebrovascular disease has also been recognized. In the past decade lipid abnormalities have been recognized in SLE patients that are "proatherogenic". These include elevated LDL cholesterol, low HDL cholesterol and elevated triglyceride levels that are not due to nephrotic syndrome. Careful clinical studies suggest that conventional risk factors such as age, sex, smoking, hypertension, etc., do not completely account for the prevalence of premature

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atherosclerosis. Indeed, there appears to be an element of risk conferred by the lupus process itself We postulate that this mechanism of the SLE associated risk lies in autoimmune events that perturb lipid homeostasis in the direction of elevated triglycerides and cholesterol. We further suggest that part of this effect is due to an immune response to lipoprotein lipase which occurs in 50% of SLE patients and promotes hypertriglyceridemia. In addition, autoantibodies to apolipoprotein A-1, Apo B and Apo E may perturb lipid transport and promote decreased HDL cholesterol and increased LDL cholesterol. Our plan is to combine our expertise in autoantibody research with epidemiologic methods. We will conduct a prospective study of SLE patients and their matched controls to evaluate these immune responses on lipid levels, in the presence of conventional risk factors and confounders, and their association with premature atherosclerosis. Recognition of autoimmune mechanisms that promote elevated triglycerides could lead to specific interventions as therapy or even possibly prevention of premature atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIGEN SPECIFIC RESPONSES TO BORRELIA Principal Investigator & Institution: Benach, Jorge L.; Professor, Molecular Genetics and Microb; Molecular Genetics & Microbiol; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 01-DEC-1993; Project End 31-MAY-2003 Summary: (Adapted from the applicant's abstract): The main and long term goal of this application is to understand the mechanism of action of bactericidal antibodies in Borrelia infections. A number of monoclonal antibodies have been discovered that can kill Borrelia burgdorferi without the assistance of complement, and the Fab fragments of the antibodies have the same bactericidal activity. Earlier studies showed that these antibodies function by lysis of the outer membrane in a Ca++ dependent medium process. This application is based on the hypothesis that complement independent bactericidal antibodies represent a novel and fundamental mechanism of host resistance in infections with Borrelia, and possibly in infections with other bacteria. The Research Plan is based on three underlying hypotheses that support the main goal of this application to characterize the mechanisms by which bactericidal antibodies can destroy Borrelia spp. The first approach will be to examine the antibodies themselves for possible catalytic properties which could result in a breakdown of the antigen leading to changes in the physical association of the antigen with other outer membrane molecules. The possibility that the antibodies could induce unique conformational changes in their antigens, which in turn could affect the topology and integrity of the outer membrane will also be evaluated. The second approach will be to test the hypothesis that the antibody-antigen complex induces the activation of lytic enzymes through an outer membrane signal transduction mechanism. Specifically, the identification and role of lipases and phospholipases in Borrelia will be evaluated. Such enzymes exist in these organisms and should be involved in the lysis of the outer membrane. If this mechanism of killing Borrelia is found to occur, it will represent a novel, and overlooked form of host defense. The third approach will be to test the possibility that bactericidal antibodies are a major form of host defense in Borrelia infections. Passive immunization studies will be conducted with the bactericidal antibodies in complement deficient (transgenic) mice to determine their role in preventing infection in a complement independent manner. Other studies will be involved in raising targeted bactericidal antibodies to antigens expressed in vivo. The possibility that the bactericidal antibodies may select more invasive phenotypes will also be evaluated.

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

Project Title: APO E GENOTYPE AND HDL CHANGES WITH EXERCISE TRAINING Principal Investigator & Institution: Hagberg, James M.; Professor; Kinesiology; University of Maryland College Pk Campus College Park, Md 20742 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAY-2004 Summary: (Adapted from the Applicant's Abstract): Abnormal plasma lipids are a major modifiable risk factor for cardiovascular (CV) disease in older persons. Polymorphic variation at numerous gene loci independently and via interactions with environmental factors affect plasma lipid levels. A cross-sectional study and preliminary data suggest that apolipoprotein E (APO E) genotype affects the HDL-C and HDL2-C increases that occur with exercise training. Thus, in healthy, sedentary, middle-aged and older subjects, the investigators will test their primary hypothesis: HDL-C and HDL2-C levels increase more with exercise training in APO E2/3 than in APO E3/4 genotype individuals. Preliminary data also indicate that lipoprotein lipase (LPL) Pvull genotype affects HDL-C and HDL2-C increases resulting from exercise training. Thus, they will test their secondary hypothesis: HDL-C and HDL2-C levels increase more with exercise training in LPL Pvull -/- than in LPL Pvull +/+ or +/- genotype individuals. Exploratory analyses will determine if variations at another LPL and 3 hepatic lipase (HL) gene loci affect the exercise training-induced HDL-C and HDL2-C increases and if, as with preliminary data, LPL and HL activities change differently with exercise training among genotype groups. After screening subjects for APO E genotype, they will be stabilized on an AHA Step I diet. Subjects then complete Baseline Testing, 6 months of exercise training and Final Testing. If VO2max, body composition, or intra-abdominal fat change differently among genotype groups with exercise training, they will be included in linear regression models to assess the independent effects of genetic and non-genetic variables on lipid changes with exercise training. Results consistent with the hypotheses will identify persons who obtain the greatest CV disease risk reductions, resulting in the optimal stratifying of exercise training to those benefiting the most. Conversely, identifying persons who will improve their lipoprotein lipids the least with exercise training would allow them to focus on interventions that might be more efficacious for them. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: BEHAVIOR MODIFICATION AND PHARMACOTHERAPY FOR OBESITY Principal Investigator & Institution: Wadden, Thomas A.; Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: Obesity is one of our nation's most serious health problems. The treatment of this disorder experienced a serious setback last year when two popular weight loss medications -- fenfluramine and dexfenfluramine -- were withdrawn from the market because of concerns that they were associated with valvular heart disease. Despite this unfortunate occurrence, it appears that pharmacotherapy will play an increasingly important role in the management of obesity in the next decade. In November 1997, the Food and Drug Administration approved sibutramine, a serotonin and norepinepherine re-uptake inhibitor, for "weight loss and maintenance of weight loss". Orlistat, a gastric and pancreatic lipase inhibitor, is now being considered for similar approval, with

Studies

9

several other medications likely to follow. Previous studies indicate that optimal weight losses and improvements in health are likely to be obtained when behavioral and pharmacologic interventions are combined. Behavior therapy facilitates adherence to exercise and medication recommendations, whereas pharmacotherapy, by reducing hunger and increasing satiety, aids efforts to consume a reduced calorie diet. Long-term pharmacotherapy also holds promise of improving the maintenance of weight loss, a shortcoming of behavioral treatment. The proposed study will examine, in an 18-month trial, the separate and combined effects of behavior therapy and pharmacotherapy for obesity. A total of 296 obese men and women (BMI greater than 32 kg/m2) will be randomly assigned to one of four conditions: 1) Medication (i.e., sibutramine) Plus Standard Care; 2) Medication Plus Individual Behavior Modification (provided by a physician in brief visits); 3) Medication Plus Group Behavior Modification; or 4) Group Behavior Modification Alone. We predict that subjects treated by medication, combined with either individual or group behavior modification, will achieve significantly greater weight losses and improvements in health than those treated by Medication Plus Standard Care. This will result from the latter subjects' significantly better adherence to diet, exercise, and medication recommendations. We also predict that subjects treated by medication plus behavior modification (in individual or group sessions) will achieve significantly greater weight losses (particularly during the last 9 months) than persons who receive Group Behavior Modification Alone. If confirmed, the above findings will have important implications for treating obesity in primary care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL SIGNALING: MACROVASCULAR COMPLICATIONS OF DIABETES Principal Investigator & Institution: Bornfeldt, Karin E.; Pathology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 30-NOV-2005 Summary: (provided by applicant): A majority of people with diabetes die of cardiovascular disease caused by atherosclerosis that is accelerated by diabetes. The factors that drive diabetes-accelerated atherosclerosis are still poorly understood. Our recent studies on a new porcine model show that diabetes in combination with elevated lipid intake causes increased accumulation and proliferation of arterial smooth muscle cells (SMCs) in lesions of atherosclerosis. The increased SMC proliferation occurs concomitant with hyperglycemia and elevated levels of plasma triglycerides. High glucose levels are not sufficient to induce SMC proliferation, but certain fatty acids common in triglycerides (oleate and linoleate) stimulate SMC proliferation in the presence of insulin-like growth factor I (IGF-I). We propose that diabetes leads to an increased amount of IGF-I and of lipoprotein lipase in lesion macrophages, and that lipoprotein lipase degrades triglycerides into free fatty acids that act in synergy with IGF-I to stimulate SMC proliferation. Our goal for the next five years is to address the following questions: 1. Do oleate and linoleate enhance the growth-promoting effects of IGF-I on SMCs? 2. How do oleate and linoleate synergize with the growth-promoting action of IGF-I in SMCs? 3. Does lipoprotein lipase produced by lipid loaded macrophages increase SMC proliferation by generating oleate and linoleate? 4. Does glucose or lipids associated with diabetes stimulate SMC proliferation, lipoprotein lipase and IGF-I in lesions of atherosclerosis and does lack of macrophage-derived lipoprotein lipase result in reduced SMC proliferation? We will use several animal models of diabetes-associated atherosclerosis, isolated arterial SMCs for signal transduction studies as well as a co-culture model of monocyte derived macrophages

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and SMCs. Increased understanding of the regulation of SMC proliferation and accumulation in diabetic lesions of atherosclerosis may provide the basis information necessary for development of highly specific drugs that can prevent lesion progression and formation of vulnerable lesions that are likely to cause the clinical symptoms of cardiovascular complications in diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELL SURFACE ACTIVITIES IN LIPOPROTEIN CATABOLISM Principal Investigator & Institution: Orlando, Robert A.; Assistant Professor; Biochem and Molecular Biology; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 18-SEP-2000; Project End 30-NOV-2003 Summary: adapted from applicant's abstract): Studies in this application propose to investigate this apparent synergistic relationship between HSPG and LRP or megalin, that is necessary for lipoprotein/lipase clearance by cells. Using quantitative biochemical procedures we will determine if ligands are 1) transferred to the endocytic receptors for internalization following their initial binding to HSPG, or 2) if the HSPG and endocytic receptors are cointernalized with bound ligand. These studies will aid in determining if LRP and megalin can regulate ligand sequestration or lipolytic enzyme activities by controlling the amount of HSPG that is present on the cell surface through endocytosis. We also plan to identify the proteoglycan-like molecule that coprecipitates with megalin and LRP, and determine if disrupting its interactions with LRP and megalin prevents the uptake of lipoproteins by cells. As a second goal, studies are proposed to quantitatively evaluate the changes in LRP and megalin expression during adipocyte differentiation, and assess the functional role of these receptors in intracellular lipid accumulation. Supporting data have found that expression of LRP and megalin in differentiating adipocytes is responsive to glucocorticoid- and cAMPdependent signaling pathways. Based on this observation the applicant plans to identify and characterize the cis- and trans-activating elements in the promoters of LRP and megalin that are responsible for regulating their expression levels during adipocyte development. Together, these studies will help 1) better define the functional roles of LRP and megalin in lipoprotein clearance, 2) begin to understand the molecular basis of their tissue-specific expression, and 3) advance our knowledge of cardiovascular health and disease such as atherosclerosis and obesity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CENTRAL OOBESITY SYNDROME IN A SUBSET OF TYPE 1 DIABETES Principal Investigator & Institution: Brunzell, John D.; Prpfessor of Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-SEP-1976; Project End 31-MAR-2007 Summary: (provided by applicant): Project 2 started as an ancillary study of lipoprotein metabolism to the NIH sponsored clinical trial of intensive diabetes therapy in type 1 diabetics to prevent microvascular disease called the Diabetes Control and Complication Trial (DCCT). The Epidemiology of Diabetes Intervention and Complications (EDIC) is a ten year non-interventional follow-up of DCCT to evaluate the natural history of macrovascular and nephropathy complications in type 1 diabetes. In DCCT, we found that atherogenic small dense LDL were increased with hyperglycemia, microalbuminuria and were increased in that subset of subjects who gained excess

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weight as a complication of intensive diabetes therapy during DCCT. Those who gained weight with intensive diabetes therapy were centrally obese, insulin resistant, hypertensive, dyslipidemic and had type 2 diabetic parents. This suggests they had inherited the metabolic-central obesity syndrome in addition to type 1 diabetes. This new proposal will use the phenotypes of 1) excessive weight gain with intensive diabetes therapy and 2) the presence of small dense LDL particles as markers of the central obesity-insulin resistance metabolic syndrome that occurred in this subset of type 1 subjects during intensive diabetes therapy. These markers of the central obesity syndrome will be used to predict the occurrence of cardiovascular events and the development or progression of microalbuminuria during the course of EDIC. Candidate genes for development of the central obesity syndrome and for the interaction of excess weight gain with the development of hypertension will be examined. Intraabdominal fat by CT scan and postheparin plasma hepatic lipase will be measured to further develop the phenotype associated with the excessive weight gain with intensive therapy and with development of nephropathy in the Seattle cohort and three Minnesota cohorts of EDIC. The development of the central obesity syndrome with intensive diabetes therapy in type 1 diabetic patients may predispose them to increased risk of cardiovascular disease and nephropathy. If so, modifications of clinical therapy will need to be made in this subset of individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZATION OF A NOVEL LYSOPHOSPHOLIPASE Principal Investigator & Institution: Huang, Ying; Pharmacology; Upstate Medical University Research Administration Syracuse, Ny 13210 Timing: Fiscal Year 2002; Project Start 02-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Numerous studies have demonstrated that phospholipids and lysophospholipids act as lipid mitogens that affect cell proliferation and survival by altering various cell signaling pathways. Intracellular levels of phospholipids and lysophospholips are tightly regulated by their respective lipases and thus, the expression and activity of these enzymes is critical for cellular homeostasis. We have cloned a cDNA that encodes a novel putative lysophospohlipase. In view of its predicted molecular mass of 34 kDa, we have named it LPL34 (lysophospholipase 34). Our preliminary results indicate that the LPL34 mRNA is highly expressed in normal colon mucosa but absent or reduced in established colon cancer cell lines. Analysis of primary colon tumors and their matching normal tissues also revealed that the expression of LPL34 is absent or reduced in 4/4 tumor tissues. Consistent with these results, expression of exogenous LPL34 in cancer cells lacking endogenous LPL34 results in growth inhibition. We have proposed studies to further examine the role of LPL34 in digestive diseases such as colon cancer. We will analyze a larger pool of fresh-frozen and paraffin-embedded tissue specimens for the expression of LPL34 at both mRNA and protein levels. We will also investigate a correlation between LPL34 status and clinicopathological features. To investigate the molecular basis of LFL34-mediated growth suppression, we will study the effect of LPL34 on PI3-K/Akt and ERKdependent mitogenic and survival signaling pathways. To determine whether lipase activity is critical LPL34-mediated growth suppressive effect, site-directed mutagenesis approach will be used to mutate the conserved lipase motif 'GHSMG' and effects of mutated LPL34 on cell growth and mitogenic signaling pathways will be investigated. These are exploratory /developmental studies that, upon conclusion, will provide us with sufficient new data and reagents that will form the basis of future in-depth studies

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Lipase

investigating the molecular mechanism(s) of action of this novel lysophospholipase in general and its role in the digestive diseases in particular. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMMON VARIANTS IN CANDIDATE GENES AND PREMATURE MI RISK Principal Investigator & Institution: Schwartz, Stephen Marc.; Assistant Professor; Epidemiology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-AUG-2004 Summary: (Adapted from Investigator's Abstract) Inherited factors play a role in the pathogenesis of myocardial infarction (MI), and there is growing interest in identifying common genetic susceptibility markers that interact with common environmental exposures to contribute to the occurrence of MI in the population. The preliminary data address the contribution of common genetic and environmental factors to the risk of MI among women under 45 years of age. Those data show that common polymorphisms in genes coding for two clotting factors, coagulation Factor V and coagulation Factor II, are risk factors for MI only among cigarette smokers in this sample. These relationships, and others observed, provide strong evidence of gene-environment interactions between thrombotic and atherosclerotic factors in early-onset MI. The plan is to extend this work to investigate the relationship of common putative susceptibility genotypes to the occurrence of early-onset MI in both men and women. One intent is to determine whether the risk of early-onset MI is related to interactions between environmental factors (e.g., cigarette smoking, exercise, alcohol consumption) and common polymorphisms in genes coding for thrombotic factors (coagulation Factor V, coagulation Factor II, plasminogen activator inhibitor-1, and beta-fibrinogen) and atherosclerotic factors (the adhesion molecule E-selectin and metalloproteinase stromelysin-1; the lipid metabolism enzymes paraoxinase, lipoprotein lipase, cholesterol ester transfer protein; and the apolipoproteins apolipoprotein E and apolipoprotein B). Additionally, there are plans to determine whether the risk of early-onset MI is related to interactions between plasma lipoprotein(a) levels (which are largely genetically determined) and environmental risk factors and/or polymorphisms in the candidate genes. Interactions among candidate polymorphisms will also be assessed. Cases will be all 18-49 year old male (n=386) and 18-59 female (n=386) residents of King, Pierce and Snohomish counties, Washington State, newly diagnosed with a first, non-fatal MI during a 3.25 year period. Demographically similar controls (n=772) will be ascertained and recruited through random digit telephone dialing. Cases and controls will be interviewed in person to assess medical and behavioral characteristics related to MI risk. A venous blood sample will be obtained and processed into aliquots of plasma and white cells. DNA extracted from the white cells will be tested using the polymerase chain reaction (PCR), PCR/restriction fragment length polymorphisms (RFLP), and oligonucleotide ligation assays to determine the genotypes of interest. Plasma will be tested for lipid, lipoprotein, and homocysteine concentrations. Analyses will address both the overall association between the genotypes and MI risk, along with posited gene-environment and gene-gene interactions. In addition to providing powerful tests of the Specific Aims, this large study will provide a unique resource for testing future hypotheses regarding the role of common genetic susceptibility factors in the pathogenesis of early-onset MI among both men and women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORTISOL, CENTRAL OBESITY, AND INSULIN RESISTANCE Principal Investigator & Institution: Purnell, Jonathan Q.; Associate Professor; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: (adapted from the application) Central (visceral) obesity contributes to an excess risk of diabetes, dyslipidemia, hypertension, and premature death from coronary heart disease. A feed-back loop model of weight regulation has emerged from recent studies of animals and humans: afferent hormones signal amount of fat mass to the central nervous system; weight regulation centers in the hypothalamus interpret these signals and control efferent systems including appetite, energy expenditure, and enzymes in the fat cell, such as lipoprotein lipase, that facilitate partitioning of energy into lipid storage. It is proposed in this grant that the hypothalamic-pituitary-adrenal axis is an effector system of hypothalamic weight regulatory centers and that increased cortisol production rates in the obese state directly regulate enzyme transcription in the fat cell to promote lipid uptake and central fat distribution. Cross sectional data from lean and obese humans using stable isotope enrichment determined by mass spectroscopy demonstrate that increases in cortisol production rates across the physiological range are associated with increased adipocyte lipoprotein lipase activity, accumulation of fat mass independent of non-fat mass, increased visceral fat, and increased insulin resistance. These findings, however, do not establish whether increased cortisol production causes, or is simply associated with these variables. To directly test whether cortisol enhances lipid uptake, fat mass accumulation, increased visceral fat mass, and insulin resistance, it is proposed to study the effect of administration of increasing doses of hydrocortisone (including doses within the physiological replacement range) in subjects with complete adrenal failure on these parameters. Finally, leading cellular candidates for the regulation of adipocyte lipoprotein lipase gene expression and fat cell differentiation, including PPAR-gamma and C/EBP, will be measured in adipose samples from the subjects in these studies to provide a mechanistic link between peripheral signaling systems such as cortisol and the adipocyte enzymes involved with fat partitioning. These studies will not only provide insight into the mechanisms of central obesity and its metabolic consequences, they also have great importance to clinicians who care for subjects with adrenal insufficiency as to the consequences of recommended replacement doses of cortisol on risk factors for heart disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ENDOCANNABINOID SITES AS THERAPEUTIC TARGETS Principal Investigator & Institution: Makriyannis, Alexandros; Board of Trustees' Distinguished Profess; None; University of Connecticut Storrs Unit 1133 StorrsMansfield, Ct 06269 Timing: Fiscal Year 2003; Project Start 30-SEP-1994; Project End 31-MAR-2006 Summary: (provided by applicant): Marijuana is the most widespread illegal drug of abuse in Western societies. Its main active ingredient, delta-9-tetrahydrocannabinol, acts by binding to specific membrane receptors called cannabinoid receptors. Activation of these receptors exerts intense effects in humans, suggesting that endogenous cannabinoid (endocannabinoid) substances may contribute in important ways to brain functions such as cognition, mood and pain sensation. Several endocannabinoid substances have been identified, including anandamide and 2-arachidonylglycerol (2AG). Anandamide and 2-AG are released from neuronal and non-neuronal cells and

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Lipase

activate cannabinoid receptors with high affinity. After release, anandamide and 2-AG undergo a rapid inactivation process, which may play an important role in terminating their biological actions. They may be taken up by cells via high-affinity transport system(s) and then broken down by distinct enzymatic activities: anandamide by fatty acid amide hydrolase (FAAH) and 2-AG by monoacylglycerol lipase (MGL). In initial studies, we have molecularly cloned a cDNA encoding for rat brain MGL and provided evidence that this enzyme may serve an important function in 2-AG inactivation. Based on these results, we propose to develop novel chemical probes that act as substrates or inhibitors for brain MGL. The first aim of the proposed research is to define the structural requirements involved in the recognition and hydrolysis of 2-AG by MGL, and develop a pharmacophore profile for MGL inhibition. In initial experiments we have molecularly cloned a cDNA encoding for rat brain MGL and developed an adenovirus-mediated MGL over-expression system in mammalian HeLa cells. Using this system, we will explore the structure-activity relationships of 2-AG hydrolysis by rat brain MGL. Specifically, we will design and synthesize novel 2-AG analogs and test them for their ability to serve as substrates or inhibitors for MGL and enhance 2-AG signaling in intact cells. The second aim of the proposed research is to develop chemically reactive 2-AG analogs, which may serve as covalent MGL ligands. Covalent, radioactively labeled ligands for MGL may be useful tools in molecular studies of this enzyme. We will design and synthesize potential covalent ligands for MGL based on the structure of 2-AG, and test them for their ability to interact irreversibly with MGL. These studies will set the stage for the elaboration of potent and selective inhibitors that target either 2-AG or anandamide deactivation and may open novel therapeutic avenues for the treatment of neuropsychiatric and substance abuse disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENZYMATIC TOOLS FOR DEGRADING TISSUE AND PRESERVING RNA Principal Investigator & Institution: Latham, Gary J.; Senior Scientist; Ambion, Inc. Austin, Tx 787441832 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-AUG-2003 Summary: (provided by applicant): Intact RNA is an obligate starting material for expression profiling technologies that can link specific molecular events with disease phenotypes. RNA isolations from tissue currently require invasive mechanical force to disrupt the cellular architecture. Such mechanical approaches are tedious and potentially inefficient. They also expose the operator to possible biohazards. As a result, the development of a "closed system" for RNA isolation is needed to enable the highthroughput recovery of RNA from tissues such as biopsies using a safeguarded platform that can process dozens or hundreds of tissues at once. We proposed to achieve this goal through the use of "MELT" (Multi-Enzymatic Liquefaction of Tissue) technology. This technology will harness the degrading power of enzymes that have evolved together as a biological tool set for the decomposition of complex food sources. We refer to this tool set as an "enzyme community." Since some enzyme communities (e.g., the secreted enzymes of bacterial pathogens) mimic the spectrum of activities needed to digest tissue, these collections are an ideal repository for tissue-degrading enzymes. We propose to characterize and blend enzyme activities to create a MELT reagent that can rapidly degrade tissues, "freeze" mRNA expression profiles, and stabilize the RNA for downstream analyses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ETIOLOGY OF NEPHROPATHY AND HYPERTENSION IN AASK PATIENT Principal Investigator & Institution: Lipkowitz, Michael S.; Medicine; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2005 Summary: (adapted from the application) We will study the etiology of hypertension and nephropathy in the majority of the 1094 African-American patients in the AfricanAmerican Study of Kidney Disease in Hypertension (AASK). The AASK study is an NIH sponsored clinical multicenter trial comparing the effect of two levels of blood pressure control and three antihypertensive regimens on progression of hypertensive nephropathy in African Americans. There is a disproportionate number of African Americans with hypertensive target organ damage, suggesting a genetic susceptibility in this population; paradoxically, few studies have been performed to evaluate such genetic predisposition to disease in this high risk population. The patients of the AASK study offer a unique opportunity to prospectively determine the genetic factors involved in hypertension and hypertensive target organ damage within a high risk and understudied population. The proposed studies will immortalize white blood cells from patients to provide a renewable source of tissue and DNA from this unique study group, and follow two approaches in assessing the etiology of hypertension, nephropathy, and their sequelae: 1. Studies are proposed to determine whether polymorphisms in candidate genes for hypertension, renal failure, and cardiac disease, including renin-angiotensin system genes, insulin resistance (beta3-adrenergic receptor and lipoprotein lipase) genes, Liddle's syndrome (beta and gammaENaC) genes, and others are related to hypertension or renal failure, severity/rate of progression of renal disease, severity/refractoriness of hypertension, electrocardiographic left ventricular hypertrophy, cardiovascular morbidity and mortality, and overall morbidity and mortality. 2. Additional studies will employ a new technique, mapping by admixture linkage disequilibrium (MALD), which uses the linkage disequilibrium caused by recent admixture of founder populations to localize genes linked to a particular phenotype within a 5-20 centiMorgan region in a genome-wide screen. By utilizing microsatellite markers from the carefully phenotyped patients of the AASK Study it should be possible to identify regions of interest containing genes associated with hypertension, renal failure, and the outcomes described above for candidate genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EVASION OF NADPH OXIDASE BY SALMONELLA LIPASES Principal Investigator & Institution: Mccollister, Bruce D.; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 31-MAR-2009 Summary: (provided by applicant): The ability of Salmonella to survive within professional phagocytes is paramount to its pathogenicity, as strains incapable of survival in mononuclear phagocytes are severely attenuated in mice. Survival of Salmonella within phagocytes is tightly associated with its ability to halt maturation of the phagosome along the endocytic pathway. We have recently discovered that Salmonella pathogenicity island 2 (SPI2)-encoded effector proteins remodel the phagosome by interfering with the TNFalpha/TNFRp55 signaling cascade that directs delivery ofNADPH oxidase-containing vesicles to the vicinity of the Salmonella phagosome. I plan to test the hypothesis that, by cleaving glucosylceramide, glucosylceramidase interferes with TNFRp55 signaling and blocks migration of NADPH

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oxidase-harboring vesicles to the vicinity of the Salmonella phagosome. The specific aims are: 1) To determine the role of glucosylceramidase in the pathogenesis of Salmonella infections. Glucosylceramidase mutants will be constructed to examine the effect on both survival of Salmonella in macrophages and inhibition NADPH oxidase trafficking. 2) To examine the effect of Salmonella-encoded glucosylceramidase on macrophage lipid metabolism. Wildtype and glucosylceramidase-deficient Salmonella will be used to infect macrophages to assess global changes in the sphingomyelin pathway. Purified glucosylceramidase will be tested for lipid metabolizing activity, and immunocytochemistry will be used to visualize the effect of glycosylceramidase on trafficking of NADPH oxidase-containing vesicles. 3) To determine the role of glucosylceramidase on avoiding IFN( activated trafficking of NADPH oxidase. In this section, I will elucidate the mechanisms by which IFN\gamma stimulates antiSalmonella activity dependent upon the NADPH oxidase. The ability of IFNgamma to stimulate glucosylceramide synthesis will be examined as well. These studies will not only enhance our understanding of Salmonella pathogenesis but will also identify potential targets for the development of new therapeutic strategies against intracellular pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENOPAUSE

EXCERCISE

AND

REGIONAL

FAT

METABOLISM

AFTER

Principal Investigator & Institution: Nicklas, Barbara J.; Associate Professor; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant) Aerobic exercise (AEX) intensity may be an important factor affecting the selective loss of abdominal fat when combined with a hypocaloric diet (DIET). The goal of this study is to determine the cellular mechanisms by which AEX intensity affects the loss of abdominal (both subcutaneous and visceral) adipose tissue under conditions of equal energy deficit in postmenopausal women with abdominal obesity. The hypothesis is that, compared to DIET alone or DIET with lowintensity AEX, DIET with high-intensity AEX will augment the loss of abdominal fat and improvements in metabolic cardiovascular disease (CVD) risk factors due to greater reductions in lipoprotein lipase (LPL) activity, and to greater increases in lipolysis, in abdominal, relative to gluteal, adipose tissue. The specific aims are: 1) to determine the cellular mechanisms by which DIET alone, or DIET combined with low- or highintensity AEX, affects region-specific fat loss by measuring changes in abdominal and gluteal adipose tissue LPL activity and lipolysis in postmenopausal women with abdominal obesity; and 2) to determine the effects of DIET alone, or DIET combined with low- or high-intensity AEX on lipoprotein lipids, glucose tolerance, and insulin levels in these women. We also will measure messenger ribonucleic acid (mRNA) levels of genes that may be involved in the regulation of regional fat storage to begin to determine how DIET with and without AEX of different intensities affects gene expression to alter body fat distribution. Body composition and fat distribution (DXA and computed tomography), LPL activity, lipolysis, mRNA expression of genes from gluteal and abdominal adipose tissue, and lipoprotein lipids and glucose tolerance will be measured before and after six months of DIET with high-intensity AEX, DIET with low-intensity AEX, or DIET alone in 120 (40 per treatment group) overweight (BMI=2535 kg/m2), postmenopausal women with abdominal obesity (waist circumference greater than 88 cm). The degree of caloric restriction during DIET will be adjusted so that total caloric deficit (about 2800 kcals/wk) will be similar between treatments. Both

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AEX groups will expend 400 kcal/wk in exercise energy expenditure and will reduce dietary intake by about 2400 kcal/wk (about 340 kcal/day). Identification of the mechanisms by which DIET with and without AEX of different intensities affects regional uptake and mobilization of triglyceride to alter body fat distribution will have important clinical implications for the development of the most effective treatment to promote the preferential loss of abdominal fat and improve CVD metabolic risk factors in older women with abdominal obesity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXTRACELLULAR REGULATION OF LIPOPROTEIN LIPASE ACTIVITY Principal Investigator & Institution: Goldberg, Ira J.; Professor of Medicine; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-APR-1991; Project End 31-MAR-2005 Summary: Lipoprotein lipase (LpL) is the principal enzyme responsible for hydrolysis of triglyceride in circulating lipoproteins. Changes in LpL activity are a basic mechanism used to modulate uptake of free fatty acids and perhaps fat-soluble vitamins by tissues. Regulation of LpL involves a number of post-secretory processes. By investigating these processes basic biological insights into the interaction of proteins with heparan sulfate proteoglycans (HSPGs) have been obtained. In this renewal, a series of experiments are proposed to understand how LpL is transferred from its sites of synthesis, principally adipocytes and myocytes, to the luminal surface of endothelial cells. Aim 1 is to determine the pathways required for LPL transport across endothelial cell monolayers. We have observed that LpL transcytosis across endothelial monolayers is reduced by RAP, the 39 kDa inhibitor of the LDL receptor related protein and other receptors in this family. In this Aim we will assess the role of these receptors and HSPGs in the transcytosis of normal and mutant LpL. The importance of this pathway and the association of LpL with proteoglycans will also be studied in vivo. Aim 2 proposes to study how LPL interaction with HSPGs regulates HSPG binding. Using these mice and new mice expressing a tethered dimer of mutated LpL, the importance of LpL-HSPG interactions will be studied. Aim 3 will study how the VLDL receptor and other RAPsensitive receptor, and LpL monomizerization participate in the physiological regulation of LPL actions. We will assess the importance of LpL transcytosis pathways in wildtype and heterozygous LpL transcytosis pathways in wild type and heterozygous LpL knockout mice, the role of RAP-sensitive receptors in regulation of LpL activity with feeding/fasting, and modulation of tissue LpL in mice that cannot covert dimeric LpL to inactive monomers. These experiments will provide information about how a secreted protein transfers from the subendothelial space into the bloodstream and the importance of protein dimerization and HSPG binding in this process. Moreover by understanding the regulation of LpL activity, these investigations will may means to change human caloric and vitamin disposal; processes that are often abnormal in humans with lipoprotein disorders and diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EYE IN GRAVES DISEASE--ROLE OF ORBITAL FIBROBLASTS Principal Investigator & Institution: Bahn, Rebecca S.; Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-AUG-1991; Project End 31-JUL-2004

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Summary: Graves' ophthalmopathy (GO) is an autoimmune eye disorder closed associated with Graves' hyperthyroidsim. There is convincing experimental evidence that the orbital fibroblast (including the preadipocyte fibroblast subpopulation) is the target cell in GO. However, the autoantigen against which the immune response is directed is unknown. The thyrotropin receptor (TSHr) is a prime candidate to be the orbital autoantigen because its involvement would help to explain the close clinical and laboratory associations between GO and hyperthyroidism. In recent studies, the PI has demonstrated the present of TSHr mRNA and protein in orbital adipose/connective tissues from patients with GO, wile TSHr expression was not apparent in normal orbital tissues. In addition, she showed that orbital preadipocyte fibroblasts, cells lacking fucntional TSHr, can be differentiated in vitro into mature TSHr-bearing adipocytes. These and other findings led to hypothesize that: 1)expression of TSHr in the orbit in GO is linked to the induction of adipogenesis in orbital preadipocyte fibroblasts, and that; 2) the adipocyte TSHr is the orbital autoantigen recognized by orbital-infiltrating lymphocytes in GO. The PI plans to examine these hypotheses using our system of cultured orbital preadipocyte fibroblasts derived from pateints with GO. In specific aim I, she will define the fibroblast-like cells present in the orbit in GO and identify factors that modulate adipogenesis in these cells. Experiments in Aim II are designed to characterize the obital TSHr and to clarify the link between TSHr expression and adipogenesis in the orbi. In Aim III, she will determine whether cloned orbitalinfiltrating lymphocytes from patients with GO recognize TSHr, or other antigens that are processed "naturally" by autologous antigen-presenting cells. The main goal of the research program is to increase understanding of the orbital immune response in GO in order that novel and more specific therapeutic and preventive strategies for this condition might be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FATTY PRODUCTION

ACID

REGULATION

OF

LIVER

LIPOPROTEIN

Principal Investigator & Institution: Ginsberg, Henry N.; Professor; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Lipotoxicity involves the excess delivery of fatty acids (FA) to sites other than adipose tissue. In vivo, fatty acids (FA) can arrive at the liver bound to albumin or as components of TG (TG)-enriched remnant lipoproteins (chylomicron and VLDL). In the latter instances, FA can be liberated from remnants by the action of hepatic lipase bound to capillaries in the hepatic vascular bed or released from lysosomes after receptor-mediated internalization of remnant lipoproteins. In addition to exogenously derived FA, increased availability of FA may result form their synthesis in the liver from acetylCoA via lipogenesis. The latter pathway has been linked recently to insulin resistance and hyperinsulinemia. The liver is unique in that it is able to "unload" excess FA in bulk form by assembling and secreting apoBlipoproteins. There are few data, however, concerning the effects of FA from each of the sources described above on the two-step process of apoB-lipoprotein assembly: the first step involves the targeting of nascent apoB across the ER membrane and assembly of a lipid-poor primordial lipoprotein, while the second step involves the bulk addition of core lipid to the primordial particle and the formation of the mature TG-rich apoBlipoprotein. Importantly, it is not known if each of the pathways involved in providing increased FA within the hepatocyte impacts equally on FA synthesis and oxidation, genes involved in TG synthesis, or genes involved in the assembly and secretion of

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apoB-lipoproteins. The link between insulin resistance/hyperinsulinemia and increased VLDL secretion is also incompletely defined. In particular, the relative importance of hepatic lipogenesis versus plasma FA uptake by the liver in the increased apoBlipoprotein secretion observed in insulin resistant animal models and humans has not been studied. The experiments proposed in this project are directed at unanswered questions related to FA regulation of apoB-lipoprotein assembly and secretion, including: (1) the effects of plasma albumin-delivered FA on each of the steps in apoBlipoprotein assembly and the expression of genes involved in maintaining hepatic lipid homeostasis; (2) the effects TG-rich remnant-like particle-delivered FA on apoBlipoprotein assembly and gene expression; and (3) the relative importance of insulin resistance/hyperinsulinemia versus increased plasma FA availability in the reaulation of apoB-lipoprotein assemblv and secretion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUTATIONS

FUNCTIONAL

CHARACTERIZATION-LIPOPROTEIN

LIPASE

Principal Investigator & Institution: Kamboh, M Ilyas.; Professor; Human Genetics; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 24-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): Lipoprotein lipase (LPL) enzyme plays a pivitol role in lipid metabolism by hydrolyzing triglyceride (TG) rich lipoprotein particles. Many diseases, including coronary heart disease (CHD), atherosclerosis and obesity seem to be directly or indirectly related to abnormalities in LPL function. A Hind lll polymorphism in intron 8 of the LPL gene has been shown to be associated with plasma TG and HDLcholesterol levels and with the risk of CHD. However, the biological mechanism behind this association is unknown. Previous studies have suggested that the intron 8 sequence, which encompasses the Hind lll site as well as intron 9 and non-coding exon 10 of the LPL gene, contain regulatory elements important for LPL transcription and translation. In this proposal we will determine if the nucleotide change in intron 8 by itself is responsible for the effect by disrupting an intronic enhancer element (Aim 1) and what is the role of the 3' region (intron 8, intron 9, exon 10) in regulating LPL transcription (Aim 2). In addition, we have identified a putative insulin response element (IRE) in non-coding exon 10 of the human LPL gene following sequence comparison of LPL genes from various species. The putative IRE sequence was targeted for mutation detection and we identified a 5 bp deletion mutation. We propose to characterize this new mutation further by performing functional and molecular studies (Aim 3). The proposed molecular and functional studies will characterize the functional significance of the LPL Hind lll and exon 10 mutations and may lead to identification and characterization of LPL regulatory elements in intragenic and 3 untranslated region of the gene. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONS OF LIPOPROTEIN RECEPTORS IN ALZHEIMER DISEASE Principal Investigator & Institution: Rebeck, G. William.; Assistant Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 05-AUG-1996; Project End 31-DEC-2002 Summary: (provided by the applicant): This application is a competing renewal of an R29 grant, "ApoE and its receptors in normal and Alzheimer's brain." ApoE

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(apolipoprotein E) remains the best-defined genetic risk factor for late onset Alzheimer disease (AD). ApoE is involved in cholesterol transport and, in AD, is associated with Abeta deposits. A number of in vitro and invivo studies have shown that apoE binds to the Abeta peptide, and affects both its clearance and its aggregation. ApoE is cleared by a family of cell surface receptors, members of the low-density lipoprotein (LDL) receptor family. We found expression of these receptors in subsets of cells in the CNS, focusing our attention primarily on the LDL receptor related protein, LRP. Polymorphisms in LRP may also affect the risk of AD, and in vitro, LRP can promote endocytosis of Abeta complexed to LRP ligands. In this proposal, we will continue to focus on endocytosis of apoE and Abeta via this family of receptors, but we will also expand our studies to look at other members of the LDL receptor family, including the VLDL receptor and apoE receptor 2. In addition, we will address newly identified functions of these receptors as signal transduction molecules. For example, in response to ligand binding, these receptors have been shown to affect calcium influx, protein phosphorylation, and glial activation. We propose that the deposition of apoE and related molecules on Abeta deposits in the AD brain affects the function of surrounding neurons and glia via these receptors. These ligand-receptor interactions could help explain the connection between amyloid deposits and formation of phospho-tau positive neurites in the AD brain. Aim 1. We hypothesize that clearance of apoE and lipoprotein-associated molecules interact with the VLDL receptor and apoEr2. A) We will test whether apoE isoforms, apolipoprotein J (apoJ) and lipoprotein lipase (LPL) are cleared by the VLDL receptor or apoEr2. B) We will test whether these receptors, present on microglia and neurons, act as clearance mechanisms for Abeta. C) We will measure the presence of apoJ and LPL in the AD brain, testing whether either affects the processes of amyloid deposition and dystrophic neurite formation. D) We will determine if polymorphisms in these genes may also affect the risk of AD. Aim 2. We hypothesize that the signaling functions of apoEr2 and the VLDL receptor cause neuronal dysfunction seen in AD. A) We will test whether these receptors interact with several hypothesized signal transduction molecules (including disabled) invivo. B) We will test whether these molecules are important for calcium influx and neurite outgrowth in neurons and activation of glia. C) We will test whether these molecules are involved in the phosphorylation of tau observed in neurofibrillary tangles of AD brains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENERAL CLINICAL RESEARCH CENTER Principal Investigator & Institution: Pak, Charles Yc.; Professor of Internal Medicine; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-DEC-1978; Project End 30-NOV-2003 Summary: The overall goal of the General Clinical Research Center (GCRC) at Dallas is to provide an optimal environment for patient-oriented investigation which leads to an improved understanding of the disease process, allows better methods of diagnosis and treatment, foster interdisciplinary collaboration, and offers training in clinical investigation. Major activities of the GCRC include; to study efficacy and safety of adding a bisphosphonate to sustained-release sodium fluoride (Neosten) and to evaluate a new formulation of sustained-release sodium fluoride combined with calcium citrate (Caflor) for postmenopausal osteoporosis; to utilize newer techniques for assessment of bone quality in osteoporosis such as nuclear magnetic resonance (NMR) microscopy, critical angle reflection ultrasound and strut analysis; determination of the pathophysiology, particularly relate to insulin resistance in gouty diathesis (renal stone formation associated with gout), its molecular genetic basis and the effects of improving

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insulin sensitivity in reversing the biochemical defects; elucidation of the genetic basis of low levels of high density lipoprotein (HDL) as related to the polymorphisms in hepatic lipase gene; characterization of phenotype and metabolic abnormalities, and elucidation of genetic defects in patients with congenital generalized and familial partial lipodystrophies; to study efficacy and safety of adding methotrexate therapy to ursodeoxycholic acid for therapy of primary billiary cirrhosis in a randomized, blinded, placebo-controlled trial; comparison of innovative and conventional treatments for management of or develop surrogate biologic markers predicting predisposition to specific skin diseases and response to therapy; to study neural mechanisms of obesityrelated hypertension in African-Americans utilizing microelectrode recordings of postganglionic sympathetic nerve activity; and development of new and reliable techniques to assess renal functions and to perform safety and dose-ranging studies of alpha- melanocyte stimulating hormone (MSH) for subsequent clinical trials of alphaMSH to treat or prevent acute renal failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENES CAUSING SPONTANEOUS OBESITY Principal Investigator & Institution: Warden, Craig H.; Associate Professor; Pediatrics; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAY-2003 Summary: The long-term goal of this research is to investigate the mechanisms of spontaneous obesity in mice. Previous work has identified 4 chromosomal regions (mouse chr. 6,7,12,and 15) or loci (QTLs) that contribute to obesity in spontaneously obese BSB mice. BSB mice were produced by a backcross of (Mus spretus x C57BL/6J) F1 x B6. Preliminary data on an available congenic mouse strains confirm that the locus on chr. 7 affects adiposity. The objective of this present proposal is to identify the genes underlying these obesity loci. Congenic mouse strains carrying the spretus chromosomal regions as donor DNA on the B6 background will be created. As co-incident QTLs for obesity, plasma cholesterol and hepatic lipase (HL) activity on mouse chr. 7 were found, the already constructed B6 HL knockout will used to test the hypothesis that alterations of HL activity determine these cholesterol and/obesity loci. BSB backcrosses with the HL KO B6 mouse will yield animals both homozygous and heterozygous for the HL knock-out. QTLs at chromosome 7; will be compared and contrasted in these two groups. The mouse chr. 6,7, and 1 loci include within their 90 percent confidence intervals, respectively, the obese, tubby, and uncoupling protein 2-genes. Molecular and biochemical studies of these candidate genes will be performed to test whether differences are likely to explain the observed effect on the trait. If there are differences in the coding portion of the spretus and B6 leptin, then the biological consequence of the differences will be tested. The chromosome 6 locus was linked to just one of the four fat pads measured in BSB mice. Leptin mRNA levels in the four fat pads will be determined to examine their correlations with plasma leptin and fat pad sizes. They have already found that spretus and B6 UCP2 differ for 2 amino acids, so uncoupling activity of UCP2 from these strains will be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC DETERMINANTS OF PLASMA LIPOPROTEINS Principal Investigator & Institution: Cohen, Jonathan C.; Associate Professor of Internal Medicin; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105

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Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 31-AUG-2004 Summary: Hepatic lipase is a 476 amino acid glycoprotein that catalyzes phospholipid and triglyceride hydrolysis in circulating lipoproteins. Hepatic lipase activity varies widely among individuals, and this variation has been associated with inter-individual differences in the plasma concentrations of high density lipoproteins (HDL), particularly the HDL2 subfraction, the rates of low density lipoprotein (LDL) synthesis and catabolism, and in the size distribution of LDL. Preliminary data from our laboratory suggest that ethnic differences in hepatic lipase activity may also be responsible for the well known differences in plasma HDL concentrations between African American and white American men. Since these studies are based on correlations between phenotypes, however, they are subject to confounding by secondary factors such as obesity and plasma triglyceride concentrations that may have independent effects on hepatic lipase activity and lipoprotein metabolism. Therefore it is difficult to infer from these studies whether or not the relationship between hepatic lipase activity and plasma lipoprotein concentrations is causal. Thus a key question that remains unanswered by these studies is "does primary variation in hepatic lipase activity cause variation in plasma lipoprotein metabolism in humans?" A second question that remains unanswered is what causes the wide variation in hepatic lipase activity observed in otherwise healthy individuals? These two questions provide the focus of this competing continuation. In the first two Specific Aims, we will compare individuals with genetically defined hepatic lipase activities to determine: i) whether genetic variation in hepatic lipase activity accounts for the well known differences in plasma HDL-C concentrations between African American and white men, and ii) whether primary differences in hepatic lipase activity cause differences in plasma lipoproteins. In the third Specific Aim, we will determine whether genetic polymoprhism in hepatic lipase contributes to the very high hepatic lipase activities commonly seen in white Men. These studies will help to determine the role of variation in hepatic lipase activity in determining plasma HDL concentrations, and LDL size distribution, two important risk factors for coronary artery disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS AND REGULATION OF HEPATIC LIPASE Principal Investigator & Institution: Deeb, Samir; Research Professor; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2006 Summary: (provided by applicant): The long-term goals of this proposal are to define mechanisms of regulation of hepatic lipase (HL) levels in humans and to determine how genetic variation at the HL gene locus modulates these levels under a variety of physiological and pathological states. HL plays a key role in lipoprotein metabolism by catalyzing the hydrolysis of triglycerides and phospholipids. A high level of HL is associated with two important metabolic risk factors for atherosclerosis: diminished concentrations of plasma high density lipoprotein cholesterol (HDLC) and an increased prevalence of small, dense low density lipoprotein (LDL) particles. Various studies, including those of our group, have shown that a significant proportion (20-25%) of the variability in HL activity is explained by a common genetic variation in the regulatory sequences of the HL gene, and that ethnic/racial background, gender and intraabdominal fat accumulation are other important modulating factors. The underlying hypotheses of this proposal are: first, that additional variants in the HL gene are responsible for variation in HL activity and the associated lipoprotein profiles in different ethnic/racial groups. Second, that high hepatic lipase activity is a risk for the

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development of cardiovascular disease. Third, that transcription factors whose activity is modulated by ligands would be excellent targets for drug design. Fourth, that HL activity is modulated by the commonly used drugs that modulated lipids. Our preliminary results support these hypotheses. The specific aims are to: 1) Identify a small set of genetic markers that would predict levels of HL activity and the associated lipoprotein phenotypes. 2) Define all hepatic lipase gene variants that are associated with risk for cardiovascular disease. 3) Identify and characterize transcription factors that regulate hepatic lipase gene expression. 4) Determine in human subjects the impact of perturbation of lipid metabolism and insulin resistance on HL activity. The results of these studies will provide insights into the metabolic and molecular bases of interindividual variation in HL activity and the associated plasma lipoprotein profiles. Key transcription factors that regulate HL activity could serve as targets for novel pharmaceutical for inducing a favorable lipoprotein profile. The genetic markers would be valuable in predicting cardiovascular risk as well as response to therapy. 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 2002; 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 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

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Project Title: TREATMENTS

GENHAT-GENETICS

OF

HYPERTENSION

ASSOCIATED

Principal Investigator & Institution: Arnett, Donna K.; Associate Professor; Epidemiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: The Genetics of Hypertension Associated Treatments (GenHAT) is proposed as a prospective study to examine whether the association between selected hypertensive genes and combined fatal coronary heart disease and nonfatal myocardial infarction in high-risk hypertensives is modified by the type of antihypertensive treatment, leading to differential risks of coronary heart disease (CHD). Such genetreatment interactions might shed important light On the variation in patient response to antihypertensive agents, and improve our ability to pick the right antihypertensive for specific patients. GenHAT will be an ancillary study to ALLHAT (the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial). ALLHAT recruited 42,515 hypertensives and randomized them to one of four antihypertensive agents (lisinopril, chlorthalidone, amlodipine, and doxazosin); followup will be completed in March, 2002. GenHAT will characterize hypertension genetic variants and determine their interaction with antihypertensive treatments in relation to CHD. DNA from frozen clots stored at the ALLHAT Central Laboratory will be used to genotype variants of hypertension genes (angiotensinogen -6, angiotensin converting enzyme insertion/deletion, angiotensin type- 1 receptor, alpha-adducin, beta2 adrenergic receptor, lipoprotein lipase, and 10 new hypertension variants expected to be discovered during the course of the study). In addition to the primary aim, a number of secondary aims will be undertaken to evaluate gene- treatment interactions in relation to other endpoints, including all-cause mortality, stroke, heart failure, left ventricular hypertrophy, decreased renal function, peripheral arterial disease, and blood pressure lowering. Because of the ethnic and gender diversity of ALLHAT, we will also assess effects of these variants on outcomes in key subgroups (age >65 years, women, African Americans, Type II diabetics), and whether the gene-treatment interactions in relation to outcomes are consistent across subgroups. This proposal has the advantages of (1) incorporation into an already funded clinical trial, and (2) collaboration with experienced investigators in genetic analysis (Drs. Boerwinkle and Eckfeldt) and clinical trials (Drs. Davis and Ford). It will, therefore, provide an important and cost-efficient contribution to the knowledge and understanding of the treatment of hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HDL GENE DISCOVERY--GENOME WIDE EXPRESSION SCREENS Principal Investigator & Institution: Rubin, Edward M.; Director, Joint Genome Institute; Division of Life Sciences; University of Calif-Lawrenc Berkeley Lab Lawrence Berkeley National Laboratory Berkeley, Ca 94720 Timing: Fiscal Year 2002; Project Start 05-FEB-2000; Project End 31-JAN-2004 Summary: Based on the incompleteness of our understanding of High Density Lipoprotein (HDL) metabolism the focus of this proposal is the identification of new genes involved in the metabolism of this lipoprotein through genome-wide expression screens. Mouse cDNA arrays containing >5000 mouse genes will be used to identify genes whose expression is altered in the liver and adrenals of several transgenic and knockout lines of mice chosen based on their characterized abnormalities in HDL metabolism. This will initially include transgenic and knockout mice for apolipoprotein

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A-I (apo A-I), Scavenger Receptor class b1 (sr- bi), Hepatic lipase (HL), and Lecithin Cholesterol Acyl Transferase (LCAT). A basic assumption in these studies is that alterations in the expression of genes known to be involved in HDL metabolism will affect the expression of other genes also participating in the metabolism of this lipoprotein. The novel genes identified from these studies will be prioritized for further biological characterization based on a variety of parameters including: level of expression change, clustering of expression patterns between mice of different HDL mutant genotypes, and sequence or expression pattern similarities to other genes known to participate in lipoprotein metabolism. The function of a limited number of novel "HDL candidate" genes (approximately 10) will be assessed each year through their over-expression in transgenic mice coupled with careful analysis of the consequence of transgene over-expression over-expression on lipoprotein metabolism. In these studies we will be utilizing a combination of new technologies and previously developed experimental substrates to address the fundamental question of what genes are directly or indirectly involved in the metabolism of HDL in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HDL PHOSPHOLIPASES

METABOLISM

INFLUENCE

OF

EXTRACELLULAR

Principal Investigator & Institution: Rader, Daniel J.; Director, Preventive Cardiology; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2004; Project Start 01-MAR-1996; Project End 31-MAR-2009 Summary: (provided by applicant): Plasma levels of high-density lipoprotein (HDL) cholesterol and its major HDL apolipoprotein, apoA-I, are inversely associated with atherosclerotic cardiovascular disease. Plasma HDL cholesterol and apoA-I levels are determined in part by the rate at which they are catabolized, but the mechanisms that modulate their catabolism in vivo remain incompletely understood. Both acute inflammatory states, such as sepsis, and chronic inflammatory states, such as the metabolic syndrome, are associated with low levels of HDL cholesterol and apoA-I, primarily due to increased catabolism. A major underlying hypothesis of this project has been that extracellular phospholipases are upregulated in response to inflammation and modulate systemic HDL metabolism through hydrolysis of HDL phospholipids. We cloned and characterized a new member of the lipase gene family that we termed endothelial lipase (EL). In the current cycle of this project, we have demonstrated that overexpression of EL in mice causes markedly reduced HDL due to increased catabolism, and antibody inhibition of EL in mice causes increased HDL due to reduced catabolism. In this competing renewal proposal, we will focus our efforts on EL toward achieving a greater understanding of its structure-function relationships, metabolic interactions with other genes that influence HDL, association with atherosclerosis, and its relationship to human physiology and pathophysiology. Specific Aim 1: To investigate the differences between EL and its highly homologous relatives LPL and HL with regard to the molecular basis of the lipid and lipoprotein preferences of EL compared with LPL and HL. Specific Aim 2: To test the hypothesis that in the liver, EL interacts with HL and SR-BI to influence HDL metabolism, selective uptake of cholesterol, and reverse cholesterol transport. Specific Aim 3: To determine the effects of chronic hepatic-specific EL expression on atherogenesis in mice. To compare these results with the effects of endothelial-specific EL expression on atherosclerosis. To test the hypotheses that endothelial EL expression influences endothelial physiology. Specific Aim 4: To test the hypothesis that EL is increased in inflammatory conditions in humans and may contribute to the reduced HDL-C levels associated with these

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conditions. A recent editorial stated: "Perhaps the most important questions concerning endothelial lipase are: a) does it play an important role in HDL metabolism in humans, and b) does it play a significant role in atherogenesis?" This proposal addresses both of these issues and also addresses key structure-function questions and potential genegene interactions with regard to EL and its effects on HDL metabolism. The results of these studies should provide important new insight into the role of EL in HDL metabolism and atherogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEPATIC METABOLISM OF DIET DERIVED LIPOPROTIENS Principal Investigator & Institution: Cooper, Allen D.; Professor; Palo Alto Medical Foundation Res Inst 795 El Camino Real Palo Alto, Ca 94301 Timing: Fiscal Year 2002; Project Start 01-JUL-1986; Project End 30-NOV-2003 Summary: The overall objective is to understand how chylomicron remnants contribute to atherosclerosis. The goal of the current proposal is to elucidate the mechanisms of the hepatic removal of these particles. Remnants accumulate in the blood during the postprandial period implying that there are times when their removal becomes limiting. The hypothesis to be tested is that the initial rate of chylomicron remnant removal is determined by the number of LDL receptors, and the capacity of the liver to sequester the particles before internalizing them (sequestration space). The size of the sequestration space is defined by heparan-sulfate-proteoglycans, and the affinity of the space for remnants is modified by the presence of hepatic lipase. The steady state rate of removal is determined by transfer from sequestration to LDL receptors and the LRP. The latter, is determined in part, by co-factors, particularly hepatic apoE. Three specific aims are proposed. First, to complete studies utilizing the isolated perfused mouse liver to characterize the remnant removal process. Isolated mouse liver perfusion was validated as a technique for studying remnant removal. Data demonstrates that both the LDL receptor and the LRP are saturable components of this process, and that there may be an additional mechanism for removal; apoE is absolutely required for rapid remnant removal, but the hepatic secretion of apoE is required for only one component of the process. Mice deficient in LDL receptors and the LRP, as well as apoE, will be utilized to complete these studies. Second, methodologies will be developed to determine the size of the sequestration space and the rate of egress from this space. The use of confocal microscopy with fluorescent labeled remnants and fluorescent markers for both endothelial cells and hepatocytes will allow determination of where remnants are accumulating, what fraction of the accumulated remnants are in the space of Disse, and the rate at which they leave this space. A multi-compartment model for analysis of the isotope removal data is being developed to determine the affinities and capacities of the components of the removal process. Using the animals of the third specific aim, this will identify which molecules contribute to these components. As a back up strategy, cell separation techniques can be used to accomplish the goals of the first two methods. The third specific aim will examine the nature of the determinants of the process. Mice that express varying fixed levels of LDL receptors will be used to study the role of this molecule in initial removal, as well as egress from sequestration. A similar strategy will be utilized for the LRP by creating truncated but functional, LRP-like molecule. Mice with different isoforms of apoE will be studied to evaluate how this affects its function as a co- factor, and as a portion of the capture mechanism. This group of studies will also evaluate the role of LPL in remnant removal in the liver. In the last group, the amount, location and enzymatic activity of hepatic lipase in the liver will be varied, to learn whether it serves as a co-factor for the LRP, or whether it serves as a determinant

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for the sequestration space, or both. In addition, attempts will be made to vary the syndecan content of the liver to test the role of this HSPG as a major determinant of the sequestration space. Together, it is anticipated that these studies will provide a concrete model for remnant removal, as well as identify the key elements in this mechanism, at which therapeutic intervention might be directed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIGH-DENSITY LIPOPROTEIN SPECIES--STRUCTURES AND ROLES Principal Investigator & Institution: Kane, John P.; Cardiovascular Research Inst; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUL-1984; Project End 31-AUG-2006 Summary: (Provided by applicant): This project is directed at understanding the native molecular speciation of high density lipoproteins, the functional roles of individual HDL species, and the processes by which they are generated and catabolized. It also includes study of the influence of mutations and polymorphisms in key genes involved in HDL metabolism with the objective of identifying genomic determinants of HDL speciation and the genetic basis of HDL deficiency disorders. Specific Aims: 1) To complete the isolation and characterization of the native molecular species of human HDL using selected affinity immunosorption. The stoichiometry of constituent proteins and lipids in those species will be established by immunochemical methods and mass spectroscopic analysis. 2) To continue to isolate novel proteins from human HDL and elucidate their gene structures. Candidates are proteins discovered by mass spectroscopic analysis that are not present in sequence databases. 3) To characterize the HDL species that are substrates and products of SR-Bl, -hepatic lipase (HL), phospholipid transfer protein (PLTP), and - mediated reactions. 4) To develop methods for quantitative measurement of individual HDL species in plasma. 5) To study the composition and distribution of plasma HDL species of HDL deficient subjects. 6) To determine the impact of mutations andpolymorphisms in the HL, PLTP, SR-BI, the ABCA1 transporter, and apolipoprotein L genes on the metabolism of individual molecular species of HDL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IDENTIFICATION OF LIPOPROTEIN AND OBESITY RELATATED QTLS Principal Investigator & Institution: Blangero, John C.; Scientist; Southwest Foundation for Biomedical Res San Antonio, Tx 782450549 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2007 Summary: (provided by the applicant): The overall goal of Project 5 is to identify genes and functional polymorphisms that affect quantitative measures of atherosclerosis, NIDDM, and obesity in Mexican American families. The particular focus of Project 3 is on following up significant evidence of linkage and association that has been detected in the current grant period. Two chromosomal regions will be the primary targets of this effort, a region on chromosome 2 that has shown linkage to a quantitative trait locus (QTL) for leptin levels (LOD=7.5) and association between leptin levels and polymorphisms in the pro-opiomelanocortin gene (p<0.005) and a region on chromosome 15 that has shown linkage to a QTL for a variety of HDL size phenotypes (LODs 2.1 to 3.8) and association between these traits and a variant in the promoter region of the hepatic lipase gene (p<0.001). The previously detected associations with

28

Lipase

strong candidate genes in these two regions will be exploited to focus the initial search on polymorphism in or near these genes. To identify single nucleotide polymorphism (SAPS) in these genes, 20 kb in and around pro-opiomelanocortin and hepatic lipase will be sequenced in 48 individuals from the families that show linkage to these regions and associations with previously typed markers in these genes. All SAPS will be genotyped that have a frequency of at least 5% in the set of 500 individuals in 10 large polymorphism will be initially assessed using combined linkage/disequilibrium and conditional measured genotype methods. When all polymorphism in a given region have been genotype in the 10 large pedigrees, newly developed statistical functional gnomic methods will be applied that are designed to identify functional polymorphism by teasing apart variants which affect the trait from those in linkage disequilibrium with them. SAPS showing evidence of association will be typed in a second set of 500 individuals for replication. Finally, Project 3 will also genotype 50 micro satellite markers in new regions of interest identified by Projects 1 and 2 for purposes of finemapping as well as 20 SAPS in positional candidate genes in these new regions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INNER CITY TOXICANTS, CHILD GROWTH AND DEVELOPMENT Principal Investigator & Institution: Wolff, Mary S.; Professor; Community and Preventive Med; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2004; Project Start 01-NOV-1998; Project End 31-OCT-2008 Summary: (provided by applicant) Two classes of industrial chemicals with endocrinedisrupting capability-the phthalates and the alkylphenols-have become widely dispersed in the urban built environment, and significant levels of phthalates are now nearly ubiquitous in the bodies of Americans. Highest exposures occur in children and in minorities. Infants and children appear especially susceptible to disruptors, because of their disproportionately heavy exposures and the vulnerability of their still forming organs to any disruption of the hormonal signaling that irreversibly shapes early development. Yet little is known, either of children's pathways of exposure, or of the human developmental toxicity of EDs. To address these gaps, the Mount Sinai Center for Children's Environmental Health and Disease Prevention Research proposes, 1) to characterize the levels and sources of children's exposures to contemporary-use EDs in the urban built environment; 2) to study relationships between EDs and neurobehavioral development; 3) to study relationships among ED exposures, diet, physical activity, and somatic growth; 4) to characterize previously unexplored enzymatic polymorphisms that may modulate individual susceptibility to EDs; and 5) to develop and deploy culturally appropriate, evidence-based strategies in East Harlem to improve children's diets, increase physical activity, reduce obesity, reduce ED exposures, and promote good health. Project 1, the Community-based Prevention Research Project (CBPR), Growing Up Healthy in East Harlem, is built on a longstanding partnership with the East Harlem community. It will study levels and sources of urban children's exposures to EDs and assess relationships among ED exposures, diet, physical activity, obesity, and use of personal care products. Project 2, an ongoing prospective epidemiological study, will analyze new and previously banked biological samples to examine associations between pre- and postnatal exposures to EDs and growth and development in a cohort study of urban children. This project will also continue to assess the developmental effects in this cohort of early exposures to neurotoxicants-organophosphates, pyrethroids, PCBs, and lead-that have been its focus for the past 5 years. Project 3, a molecular genetic study, will assess gene-environment

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interactions that may influence individual susceptibility to EDs by identifying and characterizing polymorphisms and variations in expression levels of PON1, lipase, and UGT-glucuronyltransferase enzymes involved in ED metabolism. A new Community Outreach and Translation Core (COTC) will use scientific information from the Center to educate and empower community leaders in East Harlem and to inform policy makers and health professionals regionally and nationally about links between the urban environment and children's health. The Center will contain an Exposure Assessment Core that collaborates with the laboratories of the Center for Disease Control and Prevention (CDC) National Center for Environmental Health, a Biostatistics and Data Management Core and an Administration Core. The Center will support two new investigators in children's environmental research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIPID BINDING PROTEINS IN OBESITY/DIABETES SYNDROMES Principal Investigator & Institution: Bernlohr, David A.; Professor and Head; Biochem/Mole Biol/Biophysics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 12-AUG-1998; Project End 30-JUN-2006 Summary: (provided by applicant): In the United States, one in every three individuals is considered very overweight or obese. More than a cosmetic issue, obesity is a positive correlate to cardiovascular disease, hypertension, atherosclerosis and diabetes. The discovery of leptin as an adipocyte-derived secreted cytokine has expanded our view of the fat cell beyond being a repository for caloric excess to a dynamic cell type functioning in the assessment and integration of overall energy homeostasis. The focus of the laboratory is on the linkage between obesity, fatty acid metabolism and lipolysis with an emphasis on fatty acid trafficking in the adipocyte and NIDDM. The laboratory studies fatty acid carriers of the adipocyte, specifically the products of the FABP4 and FABP5 genes. In fat cells, these proteins form 1:1 non-covalent complexes with fatty acids and other hydrophobic monoacyl lipids. aP2 (FABP4) and KLBP (FABP5) each form a physical complex with the hormone-sensitive lipase (HSL), the key rate-limiting enzyme of lipolysis that hydrolyzes triacylglycerol to fatty acids. Consistent with the association of aP2 with the HSL, FABP4 null mice exhibit reduced basal and hormonestimulated lipolysis suggesting fatty acid binding proteins affect the process by removing end-product fatty acids from the lipase reaction and facilitating their efflux from the cell. FABP4 null mice exhibit protection from obesity-linked insulin resistance without reduction in fat mass or leptin levels. Double FABP4-FABP5 null mice have lower fat mass and leptin levels. Conversely, transgenic mice that overexpress KLBP in fat cells under the aP2 promoter, have elevated fat cell mass and are more insulin resistant than are wild type animals. We hypothesize that FABPs stimulate lipolysis via interaction with HSL and that the disruption of the interaction results in a quantitative difference in both the molecular species and abundance of fatty acids that are lipolyzed from the fat cell. Such changes in lipolysis-derived fatty acids affect the availability of fatty acids linked to the development of insulin resistance. To test this hypothesis we propose to: Specific Aim A: Evaluate lipolysis in vivo and in situ from low and high fat fed mice harboring either disrupted FABP genes or the aP2-KLBP transgene. Correlate the rate and extent of lipolysis to insulin resistance in such animal models. Specific Aim B: Examine the physical interaction of FABPs with HSL in vitro. Assess the role of FABPs in regulating the activity of HSL and map the interaction domains of the two proteins. Specific Aim C: Assess the association of FABPs with HSL in 293 cells and 3T3-

30

Lipase

L1 adipocytes using fluorescence resonance energy transfer. Examine phosphorylation/translocation of HSL and its relationship to FABP association.

the

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

Project Title: LIPID SIGNAL TRANSDUCTION /OSCILLATORY INSULIN SECRETION Principal Investigator & Institution: Corkey, Barbara E.; Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Insulin secretion oscillates, possibly due to oscillatory metabolism of glycolysis, mitochondrial energy production, anaplerosis and lipolysis. These oscillations generate important signals underlying oscillations in electrical activity, ion fluxes and, ultimately, secretion. We hypothesize that FFA may participate as coupling factors to synchronize islet metabolic signal transduction and insulin secretion and to provide communication between peripheral fat cells and islets. This may be achieved by recruiting beta cells, increasing synchrony among beta cells or enhancing responsiveness of beta-cells to glucose. We further presume that FFA and their release by hormone sensitive lipase (HSL) generate important signals that regulate insulin secretion in response to fuel stimuli and elevation of cAMP. We predict that animal models deficient in PFK-M (phosphofructokinase-M) or HSL will demonstrate the critical importance of glycolytic and lipolytic pathways in insulin secretion. Aim 1 will determine the effect of FFA on glucose-induced mitochondrial metabolic oscillations of individual cells within the intact islet. The role of endogenous FFA as a signaling molecule will be studied by monitoring the synchronized metabolic activity in the intact HSL deficient islet. Aim 2 will determine the relationship between oscillatory changes in lipid partitioning and lipolysis in beta cells and islets and GSIS and the effect of FFA on these parameters. Intracellular distribution and movement in real time of fluorescent FFA will be monitored using confocal imaging of beta cells and islets. In addition FFA and glycerol release from stimulated cells will be temporally correlated with insulin secretion and measurements made in Aim 1. Aim 3 will test the hypothesis that FFA promote secretion via direct modulation of voltage-gated L-type calcium channels. Aim 4 will test the hypothesis that oscillatory FFA release from fat cells via HSL-mediated lipolysis plays a role in synchronized insulin secretion from islets. Sequential co-perifusion of isolated fat cells and pancreatic islets will be undertaken. Aim 5 will test the hypothesis that regulation of HSL in the R-cell occurs via oscillatory inhibition by long chain-CoA. Aim 6 will study the mechanism whereby HSL-deficiency in beta-cell results in altered GSIS. Aim 7 will test mechanisms of secretory and electrical synchronization in the intact perfused pancreas and its relationship to islet and single cell studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LIPOLYTIC MECHANISMS OF PPAR ACTIVATION Principal Investigator & Institution: Plutzky, Jorge; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-activated nuclear receptors central to the transcriptional regulation of adipogenesis, glucose control and lipid metabolism. More recent work establishes PPAR expression and effects in the vasculature, including endothelial cells (EC). Despite

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these advances, major unresolved issues persist. One central unanswered question in the PPAR field is the nature of endogenous PPAR ligands, which might recapitulate the effects of synthetic PPAR agonists, or how such natural mediators are produced under physiologic conditions. Similarly, despite extensive studies implicating PPARs in lipid biology, little data exists regarding the links between pathways of lipid metabolism and subsequent PPAR activation. Such insight could have major implications for metabolic disorders and atherosclerosis. Data is presented establishing lipoprotein lipase (LPL), the central enzyme in triglyceride-rich lipoprotein metabolism, as an endogenous mechanism for PPARalpha activation. In vitro and in vivo evidence, using both gain of function (LPL overexpression) and loss of function (PPARalpha-deficiency) models, support this claim. LPL-mediated PPAR-alpha activation is independent of LPL's known non-enzymatic effects and is selective as to PPAR (PPARalpha>>PPARdelta> PPARgamma), lipoprotein substrate (VLDL>>LDL>HDL), and lipase- absent with other fatty acid-releasing lipases tested. Furthermore, monoacylglycerol (MAG), a LPLspecific product, is identified as a novel PPARalpha activator contributing to these LPL responses. Our central hypothesis is that lipolysis is a major pathway for endogenous PPAR activation, with distal effects determined by the varying nature of lipoprotein substrate, lipase, and targeted PPAR. This proposal outlines experiments to define lipolytic mechanisms for PPAR activation across these same parameters. Unique contributors to LPL-mediated PPARalpha activation, as suggested by preliminary data, will be studied, including MAG as a little studied signaling molecule and mechanisms of ligand delivery. Key lipolytic variables of lipoprotein substrate and other tiglyceride lipases will be examined in terms of their PPARalpha, -delta, and -gamma effects. These studies include measures of lipolytic PPAR responses on available well-characterized VLDL and plasma samples from both mice and humans. The existence of genetic LPL variants in mouse models and in humans, which have a range of LPL activity, will be utilized in vitro and in vivo to determine how graded LPL function alters wellestablished PPAR responses. These LPL models include the otherwise lethal LPLdeficient mice rescued by transient LPL expression. Through these programmatic efforts, insight will be gained into lipolysis as a mechanism for selective endogenous PPAR activation, and its distal transcriptional effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIPOPROTEIN LIPASE AND PREECLAMPSIA Principal Investigator & Institution: Hubel, Carl A.; Assistant Professor of Ob/Gyn; Magee-Women's Health Corporation 204 Craft Ave Pittsburgh, Pa 152133180 Timing: Fiscal Year 2002; Project Start 15-FEB-2000; Project End 31-JAN-2005 Summary: Preeclampsia is a leading cause of maternal death and increases perinatal death five-fold. There is compelling evidence that maternal endothelial dysfunction contributes to the pathogenesis of preeclampsia. Hypertriglyceridemia, decreases in high density lipoprotein (HDL) cholesterol, and abnormally small-sized low density lipoprotein (LDL) particles are characteristic features of preeclampsia. We have proposed that these lipid abnormalities promote endothelial dysfunction in preeclampsia through the generation of oxidative stress. Lipoprotein lipase (LPL) plays a vital role in the clearance of triglycerides from the circulation. The importance of LPL defects in the development of cardiovascular disease is increasingly recognized. Several common variations in the LPL gene promote the triad of increased triglyceride, decreased HDL cholesterol, and small-sized LDL. The dyslipidemic effects of these functional variants are accentuated by pregnancy. In our Caucasian population, a sum total of 18.8% of preeclamptics are heterozygous for either the N291S or D9N coding

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Lipase

sequence variants of the LPL gene, compared with 4.6% of normal pregnancy controls. Accordingly, Aim 1 is to test whether these observations can be generalized to other populations. We will compare the prevalence of the four most common, functional variants in the LPL gene in Caucasians and African-Americans from western Pennsylvania, and in Icelandic women. Aim 2 is to sequence the coding and promoter regions of the LPL gene to identify other functional variants, which will then be genotyped in cases and controls. We posit that variations in the LPL gene the predispose to dyslipidemia are over-represented in women with preeclampsia. Aim 3 is to compare plasma lipids, lipid peroxidation products, and markers of endothelial dysfunction in women with preeclampsia stratified by genotype. We hypothesize that, among women with preeclampsia, those carrying LPL variants with reduced enzymatic activity will display an especially adverse blood profile. In Aim 4, we will measure plasma LPL enzyme activity in women 12 weeks postpartum to further test the hypothesis that a constitutional deficiency in LPL (hormonally and/or genetically mediated) is associated with preeclampsia. In Aim 5, we will explore the effects of heterozygous LPL deficiency on endothelial regulation of vascular function during pregnancy, using the LPL knockout mouse. This systematic approach will help to clarify the link between dyslipidemia and the pathogenesis of preeclampsia and could provide clues to prevention or treatment of the disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LIPOPROTEIN LIPASE, NUTRITION AND NERVE MYELINATION Principal Investigator & Institution: Eckel, Robert H.; Professor of Medicine,; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JAN-1990; Project End 30-NOV-2003 Summary: Lipoprotein lipase (LPL) is a hydrolytic enzyme which releases fatty acids and monoacylglyerol from nutrient-dependent triglyceride-rich lipoproteins [chylomicrons and very low density lipoproteins (VLDL)] and regulates the partitioning of these lipid fuels to tissues. This process has been studied most extensively in adipose tissue and muscle. However, LPL is also made in other sites including the nervous system, where the lipase is found in the brain, spinal cord and peripheral nerve. In the peripheral nerve, in vitro experiments have suggested, but not yet proven, that function of LPL is to enhance the uptake of chylomicron and VLDL triglyceride fatty acids to Schwann cells for myelin phospholipid synthesis. The studies outlined in this proposal will further this understanding by: 1) determining the sites of LPL expression within the peripheral nerve and defining the role of LPL in myelin synthesis nd peripheral nerve regeneration; 2) assessing the expression and regulation of peripheral nerve LPL in animal models of diabetic peripheral neuropathy; and 3) evaluating the efficacy of retroand adenovirally mediated human LPL (hLPL) gene delivery to augment myelination following peripheral nerve injury, and reverse and/or retard the neuropathy of diabetes mellitus. A combination of experiments in rodents and cultured Schwann cells will be utilized. To more specifically determine the role of the LPL in peripheral nerve in rodents (Specific Aim #1), the cells of origin and response of LPL to crush injury will be examined in normal rats and mice, and in transgenic mice without LPL in the peripheral nerve. In Specific Aim #2, several models of diabetic mellitus with already characterize peripheral neuropathy will determine if LPL expression in the peripheral nerve injury is impaired +/- crush injury. Finally, in Specific Aim #3, an important series of experiments will determine the efficacy of the delivery of LPL to augment myelination in regenerating nerves and in rodents with diabetic peripheral neuropathy. Two viral

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gene delivery systems will be evaluated for their ability to deliver hLPL to rat sciatic nerve: retrovirus-mediated gene delivery, which targets dividing cells, and adenovirusmediated gene delivery, which introduces genes into non-dividing cells. The method that better facilitates sciatic nerve recovery from crush injury will then be administered to rodent models of diabetic neuropathy in an attempt to improve peripheral nerve myelination. Overall, these studies should provide a comprehensive understanding of the role of LPL in the peripheral nerve. Moreover, we are hopeful that new insights into the treatment of peripheral neuropathies will also ensue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MACROPHAGE MECHANISMS

CHYLOMICRON/B48

RECEPTOR,

BINDING

Principal Investigator & Institution: Bradley, William A.; Professor of Medicine; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: ApoB is essential to life yet excess apoB100 or apoB48 is atherogenic and associated with increased risk of cardiovascular disease. We identified and cloned a new, unique receptor (R) for dietary triglyceride-rich lipoproteins (TGRLP), the apoB48 R. It is constitutively expressed on monocyte-macrophages (MM), including human atherosclerotic foam cells and bone marrow precursors, and endothelial cells (ECs), cells intimately involved in hemostasis and atherothrombogenesis as well as hemopoiesis, immune function and tissue nutrition. Although we have documented that the apoB48 R binds to apoB48, major questions remain on the precise mechanism(s) of binding and why normal VLDL and LDL have low affinity for this R--which microdomain of apoB48 is necessary for R binding and how the other apoB regions, apoproteins, and lipid constituents modulate binding of lipoproteins to this R. Our published and preliminary data support the hypotheses that (1) an apoB48 microdomain that is required for binding is at or near the lipoprotein lipase binding site, is not releaseable by trypsin, is not in a heparin binding domain, and is masked in normal VLDL and LDL; (2) apoB48 R binding affinity is greater in large particles (Sf greater than 100) than in small particles (Sf less than 100); and (3) apoE inhibits binding to the apoB48 R. This ensures sufficient uptake of larger nutrient-rich (lipids and lipid-soluble vitamins) dietary particles by cells responsible for tissue nutrition, immune function and hemopoiesis, cells with high nutritional requirements, and directs smaller apoB lipoproteins to the liver, as observed in vivo. We propose multiple approaches to define the R-binding apoB48 microdomain (Aim 1) and to define modulators of this interaction (Aim 2), using native, modified, and model lipoproteins, monoclonal antibodies, C-terminal truncated apoB, molecularly engineered apoB mutant constructs, and cell and ligand blotting studies. Knowledge of the basic biochemical determinants and molecular mechanisms that govern the interactions of TGRLP with the apoB48 R are crucial to meaningful intervention to prevent excess, atherothrombogenic uptake by this route while preserving sufficient nutrient uptake or, conversely, to enhance uptake in subjects with multiple pathologies due to defective or deficient apoB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF METHYLMERCURY INDUCED NEURONAL TOXICITY Principal Investigator & Institution: Aschner, Michael; Professor; Physiology and Pharmacology; Wake Forest University Health Sciences Winston-Salem, Nc 27157

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Lipase

Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's Abstract) Methylmercury (MeHg) is a significant environmental contaminant that continues to pose a great risk to human health. Considerable attention in the scientific and health policy fora is focused on the question of whether MeHg intake from a diet high in fish is associated with aberrant CNS function. A number of recent studies (Kjellstrom et al., 1986, 1989; McKeon-Eyssen et al., 1983; Grandjean et al., 1997) suggest that fetal exposure at levels attained by mothers eating fish regularly during pregnancy are associated with neurological deficits in their offspring. Astrocytes play a key role in MeHg-induced excitotoxicity. [1] MeHg preferentially accumulates in astrocytes. [2] MeHg potently and specifically inhibits glutamate uptake in astrocytes. [3] Neuronal function is secondary to disturbances in astrocytes. [4] co-application of nontoxic concentrations of mercury and glutamate leads to the typical appearance of neuronal lesions associated with excitotoxic stimulation. [5] MeHg induces swelling in astrocytes. These observations are fully consistent with MeHg-induced dysregulation of excitatory amino acid homeostasis, and indicate that a glutamate-mediated excitotoxic mechanism is involved. The working hypotheses of the proposal outline a number of critical target sites for MeHg-induced neurotoxicity. In Specific Aim 1.0 we will test the hypothesis that activation of the astrocyte-specific enzyme, cytosolic phospholipase A2 (cPLA2) and the ensuing hydrolysis and release of arachidonic acid (AA) are mediators of glutamate release upon exposure to MeHg. We will investigate the lipase(s) involved, and determine the relationship between cPLA2 activation, regulatory volume decrease (RVD), and glutamate release. In specific Aim 2.0, we will test the hypothesis that MeHg-induced increased extracellular glutamate concentrations will competitively inhibit cystine transport into astrocytes, leading to diminished supply of cysteine for neuronal glutathione (GSH) synthesis. In Specific Aim 3.0, we will test the hypothesis that modification of cysteine residues by MeHg is associated with altered glutamate transport, and that it is regulated by the chemical redox-state of reactive cysteine residues in the astrocyte-specific glutamate transporters, GLAST and GLT1. The studies will be carried out in rat primary cultures of neurons and astrocytes, as well as Chinese hamster ovary (CHO-K1) cells (where transporters can be over expressed in cells that lack the endogenous glutamate transporter). Our approach will encompass a broad array of methods, including molecular biology, electrophysiology, radiolabel trans-membrane fluxes, and electrical impedance measurements of cell volume. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEMBRANE STRUCTURE AND ENZYME ACTIVITY Principal Investigator & Institution: Brockman, Howard L.; Professor; Hormel Institute; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-MAR-1992; Project End 31-MAY-2006 Summary: (provided by applicant): Translocation of proteins to phospholipid membranes involves specific protein structures and can be triggered by the presence in the interface of a non-phospholipid lipid "second messenger," like diacylglycerol The long-range goal of this research is to understand how interactions between phospholipids and non-phospholipid second messengers regulate peripheral protein binding to interfaces and the subsequent expression of catalytic activity. Its focus is pancreatic triacylglycerol lipase (PTL) and its cofactor protein, colipase (COL), for which lipids like diacylglycerols are activators as well as lipase substrates. PTL and two other members of its gene family, lipoprotein lipase and hepatic lipase, are the primary regulators of the distribution of lipids to and from peripheral tissues. Hence, they are

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highly relevant targets in the treatment of diseases of lipid homeostasis like obesity and atherosclerosis. To function properly, the lipid-binding motif of the N-terminal domain of PTL must bind to the lipid-water interface in its catalytically-efficient or 'open' conformation. The role of the C-terminal domain of PTL in this is unclear. In the fluid lipid interfaces at which PTL functions, phospholipids and lipase substrates form dynamic complexes that mix with uncomplexed lipids. We hypothesize that complexes inhibit the rate of protein adsorption and, hence, lipolysis. We further hypothesize that once PTL and COL bind, they rearrange lipid species in the interface to help overcome the inhibition. Apolipoprotein C-II, the cofactor for lipoprotein lipase, appears to act similarly to COL despite its lack of structural homology. To test these hypotheses, we propose 1) to define the role of lipid complexes in regulating the association of PTL's domains and COL to interfaces. To accomplish this we will use radiometric and fluorometric methods to measure initial rates of COL and PTL domain binding as a function of interfacial composition and packing; 2) to determine the ability of each of the three lipid associating motifs of PTL and COL to perturb lipid lateral organization. To accomplish this we will fluorimetrically determine the extent to which each bound protein motif is able to laterally redistribute lipid species in interfaces; 3) to determine the interfacial requirements for the binding of PTL's catalytic domain in the catalyticallyefficient conformation. To accomplish this we will chemically and spectroscopically determine how PTL catalytic domain binding and conformation are regulated; 4) to define the functional similarities of the PTL-COL lipolytic system with the serum lipoprotein lipase-apolipoprotein C-II system. To accomplish this the techniques used in aims 1-3 will be applied to these proteins. With its unique focus on the role of lipid interfacial structure in regulating protein binding, this research will provide a specific mechanistic understanding of how cofactor proteins enable lipolysis to occur at physiologically relevant interfaces. More broadly, it will help to explain how lipid second messengers regulate protein translocation associated with signaling events in cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MENOPAUSE, LPL GENOTYPE AND METABOLISM AFTER WEIGHT LOSS Principal Investigator & Institution: Goldberg, Andrew P.; Professor; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2005 Summary: This research is designed to determine whether obese postmenopausal women with a common polymorphism in the lipoprotein lipase (LPL) PvuII gene, i.e. the (+) allele have less favorable metabolic responses to weight loss (WL) treatment than women without the LPL PvuII cut-site (-/-). The hypothesis is that the LPL PvuII genotype affects fasting muscle and adipose tissue and LPL activity and the metabolic responses to hypocaloric feeding-induced WL in a dose-dependent manner to affect the magnitude of the reduction of total and visceral fat, and improvements in glucose/insulin and lipoprotein lipid metabolism following WL in postmenopausal women. Specific aims determine whether obese women who are homozygous for the LPL PvuII (+) cut-site, i.e. the (+/+) genotype, have greater increases in adipose tissue LPL and decreases in muscle LPL activity and larger decreases in resting metabolic rate (RMR) and fat oxidation than heterozygotes during hypocaloric diets, that are associated with: 1) the loss of less total body and visceral fat; and 2) smaller improvements in lipid and glucose metabolism than women without the cut-site, i.e., (/-). We will study healthy, obese (Body Mass Index, 30-40 kg/m2) 50-60 year old

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women within 5 years of menopause. The statistical power to test our hypothesis is based on preliminary data showing differences in adipose tissue LPL responses to WL between LPL PvuII (+/+) and (-/-) genotypes, and requires 27 women/genotype. Subjects will be entered prospectively based on their LPL genotype to ensure a homogeneous group of obese menopausal women are studied to eliminate confounding factors of gender, age, duration from menopause and body composition on the metabolic responses to WL treatment. Metabolic studies are performed on prepared calculated weight maintaining eucaloric diets for 2-3 weeks at baseline and after 6-mo WL to ensure metabolic stability, and on hypocaloric diets after the short-term study to assess metabolic responses to negative energy balance. We will measure muscle and adipose tissue LPL activity, RMR, fat oxidation, total and visceral body fat (DXA and CT scans) lipoprotein lipids and. glucose/insulin responses during an oral glucose tolerance test. Following the post-WL metabolic evaluations, subjects enter a 6- mo follow-up period followed by metabolic testing to assess long- term metabolic adaptations and weight regain by genotype. Collectively, these findings will enhance our understanding of obesity by assessing the gene-metabolic mechanisms underlying the predisposition of some obese women to more favorable metabolic health benefits from WL. This would allow the targeting of WL treatments to women more likely to respond, and pharmacologic and other treatments to those less likely to respond to WL. This optimistic outcome would reduce prevalence of obesity and risk for CVD in older women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METABOLIC REGULATION OF LIPOPROTEIN LIPASE IN ADIPOCYTES Principal Investigator & Institution: Currie, Richard A.; Scientific Review Administrator; Wheeler Institute for Biomedical Res Jhu Bayview, Alpha Center Baltimore, Md 21224 Timing: Fiscal Year 2002; Project Start 01-MAR-1993; Project End 31-JUL-2003 Summary: (adapted from the applicant's abstract): In this application Dr. Currie plans to extend studies from the previous funding period on the role and mode of action of Nuclear Factor Y (NF-Y) in the transcriptional regulation of the lipoprotein lipase (LPL) gene during adipocyte differentiation. Five hypotheses are proposed: 1) Reiterated AThook motifs in HMG-I(Y) both bind AT-rich DNA sequences as well as stabilize the CCAAT-box complex; 2)Reversible phosphorylation of PC4 regulates the stability of NFY subunit interaction, and indirectly the CCAAT-box complex; 3)HMG-I(Y) and PC4 provide functional links between NF-Y, Oct-1 and components of the Pol II complex in the assembly of the pre-initiation complex; 4)The NF-Y complex is associated with additional, currently unidentified protein which modulate transactivation potential; and 5) The histone acetyltransferases GCN5 and P/CAF remodel the chromatin around the LPL promoter CCAAT-box through their interaction with NF-Y. In order to eventually test these hypotheses, three specific aims will be pursued: I) The functional roles of PC4, HMG-I(Y), GCN5, and P/CAF in modulation NF-Y mediated transcription will be studied. II) Additional NF-Y subunit associated components will be identified and purified and their functional properties in the native NF-Y complex studied. III) An in vitro cell-free transcription system based on purified components will be established in order to study the biochemical roles of NF-Y, Oct-1, and their associated cofactors in the transcriptional regulation of the human LPL gene. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: METABOLISM OF INTRAVENOUS LIPID EMULSIONS Principal Investigator & Institution: Deckelbaum, Richard J.; Director, Professor of Pediatrics; Institute of Human Nutrition; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 30-SEP-1992; Project End 31-AUG-2007 Summary: (provided by applicant): Our objective is to characterize pathways whereby intravenous (IV) lipid emulsions, commonly used clinically as nutritional support, deliver specific types of triglyceride (TG) to tissues and cells. With increasing recognition of the importance of omega-3 (omega-3) very long chain fatty acids (FA) (omega3-VLC FA) in multiple biological pathways, our major goal is to delineate mechanisms for delivery of these omega3 FA to different tissues, and to define the effects of this delivery on selected cellular endpoints related to cell TG and cholesterol metabolism. Recent evidence indicates that routes for blood clearance and tissue uptake of fish oil omega3 TG are very different from those of omega6 soy oil long chain TG (LCT). For example, removal of (omega3 VLCT) emulsions from blood seems to depend far less on intravascular lipolysis than does LCT emulsions. While substantial amounts of both emulsions are delivered to tissues as intact TG, this pathway is likely more important for omega3 TG particles. Omega3 TG particles are less dependent on "classical" lipoprotein receptor related clearance pathways, than are LCT. FA derived from omega3 TG appear to act as stronger inhibitors than LCT in sterol regulatory element (SRE) dependent gene expression-genes that are involved in both TG and cholesterol syntheses. The proposed research will systematically define mechanisms whereby TG composition, particle size, and specific ligand related pathways contribute to LCT vs. omega3-VLCT clearance and metabolism in different tissues and cell types. Aim 1 will use physical-chemical approaches (e.g., 13C-NMR) to clarify how omega3-TG and FA affect the properties of the emulsion particle surface, and how this in turn affects lipoprotein lipase and apoprotein E binding, structure, and function. Aim 2 utilizes in vitro cell culture experiments and Aim 3 in vivo mouse models to differentiate metabolic pathways for omega3-VLCT/FA and omega6 TG/FA, and how these differences affect expression of genes related to TG and cholesterol homeostasis. Studies in Aim 4 will test if hypotheses generated from cell and mouse models are likely to occur in humans -- by protocols whereby omega3-VLCT and LCT emulsions are infused in healthy volunteers. Our analyses will differentiate between mechanisms for clearance and metabolism omega3 vs. omega6 TG and FA. Our studies will allow new insight as to how fish oil derived emulsions reach different tissue, undergo metabolic processing, and regulate expression of certain genes, and will also provide carefully characterized models for the study of human lipid and lipoprotein metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOBILIZATION OF TRIACYLGLYCEROL STORES IN INSECTS Principal Investigator & Institution: Arrese, Estela L.; Biochem and Molecular Biology; Oklahoma State University Stillwater Stillwater, Ok 74078 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: (provided by the applicant): Unlike vertebrates, where the stored fatty acids are mobilized as free fatty acids, a great number of insects, mobilizes fatty acids as an-1, 2-diacylglycerol (DG). The mobilization of TG stores requires the action of a TG-lipase, whose activity is hormonally regulated. The substrate of the lipase (TG) is found in large intracellular lipid droplets, which are constituted by a core of TG surrounded by a complex surface layer of phospholipids and proteins. On the other hand, the TG-lipase

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Lipase

localizes in the cytosol of lipolytically unstimulated fat body cells. Lipolysis involves the interaction of the lipase with the surface of the lipid droplet. It is known that activation of lipolysis promotes both an increase of intracellular calcium concentration and activation of amp-dependent protein kinase (A-kinase) but the basic mechanisms involved in how phosphorylation-dephosphorylation reactions modulate the rate of lipolysis is unknown. Moreover, little is known about the relevance and nature of the structural and compositional changes that affect the lipid droplet when lipolysis is hormonally activated. These changes must ultimately affect the interaction of the lipase with the lipid substrate and the concomitant activation of lipolysis. DG moves from the lipid droplet to the plasma membrane by an uncharacterized mechanism. It appears that after the conversion of TG into DG on the surface of the lipid droplets, DG would be transferred to a cytosolic carrier, which in turn would target the delivery of DG across the plasma membrane. The overall goals of this project are to establish the mechanisms regulating lipolysis by determining the factors that promotes the interaction between TG-lipase and its substrate, the lipid droplet and to define the mechanism of intracellular transport of DG. Clearly the elucidation of these mechanisms is of fundamental importance in insect biochemistry and physiology. These studies will provide comprehensive information on the lipolytic process in insects and this knowledge could also contribute to the broad field of lipid metabolism and transport in vertebrates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODIFICATION OF HELICOBACTER PYLORI LIPID A Principal Investigator & Institution: Trent, Michael S.; Microbiology; East Tennessee State University Box 70565 Johnson City, Tn 37601 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The outer membrane of Gram-negative bacteria consists of a unique molecule known as lipid A that serves as the membrane anchor for lipopolysaccharide (LPS). Lipid A (endotoxin) is the component of LPS responsible for the stimulation of the host innate immune system involved in Gram- negative sepsis. The lipid A of Escherchia coli is a hexa-acylated disaccharide of glucosamine that is substituted at the 1- and 4'- positions with phosphate and glycosylated at the 6' position with two Kdo (3-deoxy-D-manno-octulosonic acid) moieties. Nine enzymes are required for biosynthesis of Kdo2- lipid A, the minimal LPS required for E. coli growth under normal laboratory conditions. Since lipid A is required for bacterial growth, it has become an interesting target for the design of novel antibacterial agents. Although single copies of the lipid A biosynthetic genes are found in nearly all Gram-negative bacterial genomes including those of Helicobacter pylori, the lipid A of the latter is underacylated with the phosphate groups either absent or modified. The primary focus of the present study is the identification of novel enzymes required for the modification of H. plyori lipid A and initial studies to evaluate the importance of such modifications during infection. Secondly, the lipid A structure of Helicobacter heilmannii will be investigated. H. pylori is now considered the causative agent of gastric and duodenal ulcers and H. heilmannii has recently been found associated with human gastritis. The specific aims of the current proposal are: (I) characterization and cloning of lipid A deacylases of H. pylori; (II) characterization and cloning of genes required for modification of the phosphates of H. pylori lipid A; (III) relevance of H. pylori lipid A modifications during infection; and (IV) isolation, purification, and structural characterization of key lipid A species of H. heilmannii. The completion of these aims will not only further the understanding of the lipid A biosynthetic pathway in H. pylori

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and H. heihnannii but also lay the foundation for new molecular insights into the pathogenesis of these unique organisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MYCOBACTERIA

BIOLOGY

OF

UNIQUE

WALL

LIPIDS

OF

Principal Investigator & Institution: Kolattukudy, Pappachan E.; Professor and Directpr; None; University of Central Florida 12443 Research Pky, Ste 207 Orlando, Fl 328283252 Timing: Fiscal Year 2003; Project Start 30-SEP-1993; Project End 31-DEC-2007 Summary: (provided by applicant): Tuberculosis remains the leading cause of preventable deaths. Natural spread of multidrug resistant tuberculosis and the potential use of such strains by terrorists make discovery of new targets for antimycobacterial therapy a very critical need. Cell wall lipids constitute a major physical and chemical defensive barrier that helps the pathogen evade the host defenses and antimycobacterial drugs. Therefore, synthesis of such unique lipids that are critical for infection can be suitable targets for new antimycobacterial drugs. Multiple methyl branched lipids such as dimycocerosyl phthiocerol (DIM) have been shown to be virulence factors. Elucidation of the biochemical reactions and the nature of the enzymes involved in the biosynthesis of such virulence factors is required for developing novel drags. To this end we propose to: 1. Elucidate the functions of lipase genes and their possible role in pathogenesis, a) Express and characterize the catalytic capabilities of lip gene products and determine whether disruption of specific lip genes will result in the absence of a specific class of acyl-lipids or absence of a specific group of esterified fatty acids, and determine whether the mutations affect virulence, b) Directly test whether the expressed lip gene products can release the acyl chains from the expressed synthases in vitro. 2. Elucidate the biological function of tes genes and their possible role in virulence, a) Express tes genes and characterize the catalytic capabilities of their products, b). Disrupt the three tes genes, determine the effects on lipid metabolism by using 14C-labeled acetate and 14C-labeled propionate as radiotracers and determine the effect of the mutations on virulence of the pathogen in the murine model. 3. Elucidate the function of wes genes, a) Express the wes genes and test whether these gene products are involved in the esterification of the methyl branched acids generated by the large synthases to the hydroxyl groups in the ultimate acceptors, b) Determine the consequences of disrupting the wes genes on lipid metabolism and test the virulence of mutants that show novel biochemical phenotypes. 4. a) Elucidate the role of the novel ( subunit in the enzyme that catalyzes the synthesis of methylmalonyl-CoA, the building block for the multiple methyl branched virulence factors, b) Determine whether disruption of accD4 and accD5 affect propionyl-CoA carboxylation, and methyl branched lipid synthesis in M. tuberculosis and its virulence. c) Determine the possible role of succinate as a source for methylmalonyl-CoA. The results of this study are likely to give information and tools for screening chemical libraries to discover new types of drug candidates directed at novel targets in M. tuberculosis and thus help in combating multidrug resistant tuberculosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETIC APPROCHES IN ATHEROSCLEROSIS RESEARCH Principal Investigator & Institution: Lusis, Aldons J.; Professor; Molecular Biology Institute; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024

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Lipase

Timing: Fiscal Year 2002; Project Start 01-JUL-1984; Project End 31-DEC-2005 Summary: The theme of this proposal is the examination of altered states of triglyceride metabolism contributing to coronary artery disease. The program addresses this theme using the mouse and human homology at the pathological, physiological, biochemical, genomic and molecular levels. Of the 5 projects in this proposal, Projects 3 will mostly involve studies in mice while 2 projects principally involve studies in humans, with 5 cores providing phenotyping, genotyping, sequencing, positional cloning, biostatistical and administrative support. Our major approach will be use genetic defects in mice and humans to identify underlying genes that contribute to altered states of triglyceride metabolism. We will emphasize familial combined hyperlipidemia (FCHL), a genetically complex disease characterized by increased plasma triglyceride metabolism. We will emphasize familial combined hyperlipidemia (FCHL), a genetically complex disease characterized by increased plasma triglyceride and/or cholesterol levels which accounts for up to 20% of premature coronary artery disease. Dr. Lusis' project will extend previous genetic studies in mice to systematically delineate genetic factors contributing to triglyceride metabolisms. Notably, will combine forces with Dr. Peltonen's Project to identify the gene affected by Hyplip1, a mutation in the mouse that causes combined hyperlipidemia and co- localizes with a homologous FCHL locus in humans. Dr. Wong's Project will focus on the structure-function properties of lipoprotein lipase (LPL), an enzyme central to triglyceride metabolism, as well as identifying genetic loci that affect LPL expression and may contribute to the LPL deficiency observed in FCHL. Dr. Reve's Project will isolate the genes, and characterize the function of the corresponding gene products, for two mouse mutations affecting triglyceride metabolism, fatty liver dystrophy (fld) and combined lipase deficiency (cld); these mutations are characterized by insulin resistance (fld) and LPL deficiency (cld) that often associated with FCHL. Dr. Rotter's project will use a combination of genome wide linkage and candidate gene association approaches to characterize genetic risk factors for coronary artery disease in human populations by identifying genes for lipid and lipoprotein variation in FCHL. Dr. Peltonen's project, using the power of a discrete population isolate (the Finn's) will perform fine mapping of a recently identified FCHL locus to isolate the predisposing FCHL gene by a positional cloning approach. Importantly, the Finnish FCHL locus is syntenic with mouse Hyplip1, and Project V will assist in isolating the mouse gene to complement and aid in the identification of the homologous human FCHL gene. Thus, the 5 projects provide a coordinated approach to identifying major genes affecting triglyceride metabolism and predisposing to coronary artery disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR REGULATION OF LPL IN SKELETAL MUSCLE Principal Investigator & Institution: Neufer, Peter Darrell.; Associate Fellow; John B. Pierce Laboratory, Inc. 290 Congress Ave New Haven, Ct 06519 Timing: Fiscal Year 2002; Project Start 23-APR-1999; Project End 31-MAR-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NOVEL BRAIN CANNABINOID LIGAND Principal Investigator & Institution: Piomelli, Daniele; Professor of Pharmacology; Pharmacology; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 14-AUG-1998; Project End 31-JUL-2004

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Summary: Marijuana is the most widespread illegal drug of abuse in Western societies. The main active ingredient of marijuana, Delta9- tetrahydrocannabinol (THC), binds to selective G protein-coupled receptors, called cannabinoid receptors. Activation of these receptors by THC exerts profound behavioral effects in humans. This suggests that endogenous neurotransmitter substances that engage cannabinoid receptors may serve important physiological and pathological functions. Although an endogenous cannabinoid ligand, anandamide, was recently identified, evidence indicates that additional ligands may exist. On the basis of our preliminary results, we propose to test the hypothesis that 2- arachidonylglycerol (2-AG), a product of phospholipid metabolism, constitutes a second endogenous ligand for brain cannabinoid receptors. To test this hypothesis it will be necessary to show that the enzymatic machinery for the formation and inactivation of 2-AG is present in neurons. Moreover, it will be necessary to demonstrate that 2-AG binds to and activates neuronal cannabinoid receptors. The first aim of the proposed research is to investigate the mechanisms responsible for 2-AG production, using rat brain neurons in primary culture. Preliminary experiments have shown that these neurons produce substantial amounts of 2-AG. The proposed studies will identify the transmembrane signalling systems and enzyme pathways underlying 2AG production. The second aim of our proposed research is to determine whether neural activity is necessary for the formation of 2-AG. Preliminary experiments have demonstrated that, in superfused slices of rat hippocampus, high-frequency electrical stimulation of an identified excitatory pathway (the Schaffer collaterals) results in the marked accumulation of 2-AG. We will examine whether 2-AG formation is stimulated by levels of neural activity that are likely to occur in vivo, and investigate the ion channels and neurotransmitter receptors involved in this response. The third aim of our proposal is to characterize the pharmacological properties of 2-AG in cortical neurons in culture. Initial experiments have indicated that 2-AG activates neuronal cannabinoid receptors. We will determine the potency, efficacy and selectivity of 2-AG in eliciting such response. The fourth aim of the proposed research is to identify the biochemical mechanisms involved in the biological inactivation of 2-AG. Preliminary results suggest that 2-AG is hydrolyzed enzymatically to arachidonate and glycerol, two products that do not activate cannabinoid receptors. We will use subcellular fractions of rat brain tissue to identify and characterize the enzyme activity that mediates 2-AG hydrolysis. In conclusion, by demonstrating that 2-AG meets the necessary criteria of an endogenous cannabinoid ligand, our studies will shed new light on the mechanisms of marijuana abuse and help develop new strategies in the treatment of neurological, psychiatric and substance abuse disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL PROTEASE FORMULATION BASED ON CROSSLINKED CRYSTALS Principal Investigator & Institution: Shenoy, Bhami C.; Altus Biologics, Inc. 625 Putnam Ave Cambridge, Ma 021394807 Timing: Fiscal Year 2003; Project Start 01-JUL-2000; Project End 31-MAR-2005 Summary: (provided by applicant): Design of stable and efficient formulation of proteins for therapeutic use as drugs has been a major focus of biotechnology and pharmaceutical companies. In the Phase I grant, we developed a stable, active formulation of protease from Aspergillus melleus, TheraCLEC-Protease, for use in the treatment of chronic abdominal pain in chronic pancreatitis and also along with TheraCLEC-Lipase and amylase for the treatment of malabsorption as a result of pancreatic insufficiency in cystic fibrosis and chronic pancreatitis. TheraCLEC-Protease

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exhibited product characteristics superior to commercially available pancreatic enzyme products. TheraCLEC-Protease exhibited a very high level of activity against casein and stability under low pH and towards various proteases present in the intestine. Moreover, in the preliminary investigations, the TheraCLEC-Protease did not show any toxicity. Based on these results in Phase II, we will prepare a drug product prototype for use in the treatment of abdominal pain in chronic pancreatitis and along with TheraCLEC-Lipase for use in the treatment of pancreatic insufficiency, azotorrhea and steatorrhea in cystic fibrosis and chronic pancreatitis patients. As a first step, we will crystallize and crosslink the protease with methods developed in Phase I Subsequently, we will mix TheraCLEC-Protease with TheraCLEC-Lipase and amylase for use in a final formulation or alone depending on the disease and type of treatment. The final formulation will be tested for efficacy in digesting proteins and fats in dogs with ligated pancreatic ducts. Using radiolabeled TheraCLEC-Protease, we will follow the lack of absorption into the systemic circulation. In addition, we will test the subacute, subchronic and long-term effects of feeding TheraCLEC-Protease in two species. If successful, a TheraCLEC-Protease prototype will provide an efficient treatment for abdominal pain. TheraCLEC-Protease will be ready to enter clinical trials, and will provide a novel treatment for pancreatic insufficiency in chronic pancreatitis and cystic fibrosis along with TheraCLECLipase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NUCLEAR ATHEROGENESIS

RECEPTOR

SIGNALING

PATHWAYS

IN

Principal Investigator & Institution: Tontonoz, Peter J.; Associate Professor; Pathology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: The long-term goal is to understand the mechanisms by which lipids regulate gene expression in vascular cells and thereby influence the development cardiovascular disease. The interaction of oxidized low-density lipoprotein with cells of the artery wall is central to the pathogenesis of atherosclerosis. Oxidized lipids not only serve as the substrate for macrophage lipid accumulation, but are also thought to contribute to lesion development through regulation of adhesion molecules and cytokines. This proposal is focused on defining the role of the nuclear receptor PPARgamma in regulating macrophage gene expression and function in response to oxidized lipids. PPARgamma is expressed at high levels in macrophage-derived foam cells of atherosclerotic lesions and is transcriptionally activated by oxidized fatty acid components of oxLDL. Multiple functions have been proposed for this receptor in macrophages, including promotion of cell differentiation, modulation of cytokine expression, and regulation of lipid uptake and metabolism. However, the true role of this transcription factor in macrophage physiology and vascular disease remains unclear. The first aim is to identify target genes of PPARgamma in monocytic cells. The identity of these genes should provide valuable insight into the nature of the processes controlled by this receptor. Preliminary data has identified the nuclear oxysterol receptor LXRa and lipoprotein lipase as regulatory targets for PPARgamma. The second aim is to characterize gene expression and function in genetically defined macrophages that over express or lack PPARgamma. The importance of PPARgamma in regulating lipid metabolism, cytokine production and mediating the biological effects of oxidized lipids on macrophage gene expression will be tested. The third aim is to analyze the role of PPARgamma in macrophage function and atherogenesis in vivo through creation of a macrophage-specific deletion of the

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PPARgamma gene. These aims are expected not only to advance our understanding of the biologic function of PPARgamma but also to clarify mechanisms by which lipid mediators regulate gene expression during pathologic processes such as inflammation and atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OBESITY--NEURAL CONTROL OF METABOLISM AND WEIGHT GAIN Principal Investigator & Institution: Levin, Barry E.; Professor and Acting Chair; Neurology and Neurosciences; Univ of Med/Dent Nj Newark Newark, Nj 07107 Timing: Fiscal Year 2002; Project Start 01-APR-1982; Project End 31-MAR-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ORGANOPHOSPHORUS PESTICIDE TOXICOLOGY Principal Investigator & Institution: Casida, John E.; Professor of Entomology; Environmntl Sci Policy & Mgmt; University of California Berkeley Berkeley, Ca 947205940 Timing: Fiscal Year 2003; Project Start 01-DEC-1997; Project End 30-JUN-2007 Summary: (provided by applicant): Organophosphorus (OP) insecticides are the principal cause of pesticide-related human poisonings. Recent restrictions on the use of chlorpyrifos and diazinon reflect continuing concern for human health, particularly children. The two principal targets of OP toxicant action are acetylcholinesterase (AChE) for acute toxicity and neuropathy target esterase (NTE) for OP-induced delayed neuropathy (OPIDN). This research focuses on noncholinergic effects, based in part on findings with collaborators on nullizygous AChE-knockout mice (AChE -/-) and heterozygous NTE-knockout mice (NTE ). AChE -/- mice are extremely sensitive to chlorpyrifos oxen (CPO) (intraperitoneal LD50 0.45 mg/kg) compared with their wildtype littermates (LD30 3 mg/kg), establishing the importance of an unidentified nonAChE target for acute lethality. The first specific aim is to identify this non-AChE target in mammals. Mouse brain proteins from AChE -/- and wild-type mice will be radiolabeled in vitro and ex vivo with [3H-ethyl]CPO. Differential protein labeling in the AChE -/- and wild-type mice with very low levels of [3H]CPO will allow selection, purification and identification of the candidate alternate target of OP acute poisoning. The second aim is to establish the function of NTE in OPIDN using mice as the model. The NTE mice have a 40% reduction in NTE activity, making them ideal for toxicological investigations. The studies will focus on the association of NTE levels with behavioral and neuropathological changes, the sensitivity of NTE and wild-type mice to ethyl octylphosphonofluoridate and other OP delayed toxicants, validation of the mouse model for OPIDN and the mechanism by which lowered NTE induces hyperactivity and delayed toxicity. The third aim is to define the mechanisms of toxicity from disruption of signal transduction pathways, and more specifically those mediated by lysophospholipase, diacylglycerol lipase, and the muscarinic acetylcholine receptor. The last goal is to define the mechanisms and significance of two secondary targets of OP pesticides: altered endocannabinoid action by OP phosphorylation at a nucleophilic site coupled to the cannabinoid receptor-1 (CB1) agonist site; kynurenine formamidase (KFase) structure and function relative to teratogenesis and diazinon oxen action in the brain. Knowledge gained on OP pesticide toxicology is also applicable to OP nerve gases as chemical warfare and terrorism agents.

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

Project Title: PERILIPIIN AND LIPOLYSIS Principal Investigator & Institution: Greenberg, Andrew S.; None; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2004; Project Start 15-JAN-1999; Project End 31-MAR-2008 Summary: (provided by applicant): Adipocyte lipolysis contributes significantly to the pathogenesis of obesity-associated diseases by increasing levels of circulating free fatty acids (FFA). FFA promote insulin resistance and type 2 diabetes. My laboratory's longterm goal is to elucidate molecular mechanisms of lipolysis regulation. The proposed studies will investigate structure / function relationships of Perilipin A (Peri A), a lipid droplet- associated phosphoprotein that regulates lipolysis mediated by hormone sensitive lipase (HSL) and non-HSL lipase(s). Peri A acts dually as a suppressor of basal lipolysis (in the absence of hormonal stimulation) and as a potent enhancer of protein kinase A (PKA)-stimulated lipolysis (in the presence of hormonal stimulation). Despite its important regulatory role, the primary sequences and the mechanism(s) by which Peri A regulates lipase actions have not been determined. Our preliminary studies indicate that Perilipin regulates lipolysis via multiple regulatory domains, which exhibit surprising lipase specificity. The proposed studies will 1) identify the minimal domains of Peri A that modulate basal and PKA-stimulated lipolysis by HSL and non-HSL lipase(s), 2) determine the relative role of PKA phosphorylation sites in PKA- stimulated lipolysis by HSL and non-HSL lipase, and 3) define the in vivo effects of altered Peri A expression, Peri A truncations and Peri A PKA site mutants using Peri A transgenic and Peri null mice. Our adipocyte and systemic studies will measure basal lipolysis, lipolytic response to beta-adrenergic agents, and antilipolytic response to insulin. These studies will provide in vivo proof of concept tests of how Peri A expression levels, regulatory domains, and phosphorylation sites regulate basal and stimulated lipolysis. These data will be directed to the prevention and treatment of diabetes, hyperlipidemia and other obesity - associated disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PERILIPINS AND CELLULAR TRIACYLGLYCEROL METABOLISM Principal Investigator & Institution: Brasaemle, Dawn L.; Nutritional Sciences; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2002; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from the Investigator's Abstract): Obesity is a health problem that is reaching epidemic proportions in the United States and has become a major and growing factor contributing to an increased prevalence of Type II diabetes and an increased risk of premature death from cardiovascular disease. Despite the need for therapeutic options to control obesity, little is known about the intracellular mechanisms that regulate fat storage and release in adipose tissue. Fatty acids, the body's major energy currency, are stored as triacylglycerols in large intracellular lipid droplets in adipocytes. The perilipins are the most abundant proteins on the surfaces of lipid droplets in adipocytes and are also found in steroidogenic cells. The proposed studies test the hypotheses that 1) perilipins facilitate triacylglycerol storage by forming a protective barrier against cytosolic lipases, and 2) phosphorylation of perilipins facilitates lipolysis in lipolytically stimulated adipocytes by attenuating the barrier to facilitate lipase access to stored triacylglycerols. The Specific Aims of the proposed research are to 1) define the structural domains of perilipin A required for its targeting

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to and embedding into lipid droplets, 2) to study how perilipin A protects stored triacylglycerols from hormone-sensitive lipase, and 3) to elucidate the role of the phosphorylation of perilipin A in the promotion of lipolysis. These aims will be tested by the expression of intact and mutant perilipin A in cultured cells that lack perilipins followed by assays for lipid storage and release, and the presence of the mutant perilipins on lipid droplets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHARMACOGENETICS OF THE STATIN RESPONSE Principal Investigator & Institution: Schaefer, Ernst J.; Professor; None; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 29-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Coronary heart disease (CHD) is the leading cause of death and disability in our society. Most CHD deaths occur in subjects over 70 years of age. Significant independent CHD risk factors are age, gender, elevated low density lipoprotein (LDL) cholesterol (C), decreased high density lipoprotein (HDL) C, hypertension, smoking, diabetes, elevated lipoprotein (a) or Lp(a) (LDL C> 50% reduction), and elevated C-reactive protein. In this response to RFA HL-03-001 (ancillary pharmacogenetic studies), we propose to study 2804 male and 3000 female participants in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), who were selected for age 70-82 years, having vascular disease coronary, cerebral or peripheral) or increased CHD risk due to smoking, hypertension or diabetes and total cholesterol levels between 4.0 and 9.0 mml/L or 151 and 340 mg/dl. In this randomized controlled trial pravastatin decreased LDL C 34% and triglyceride 12% and raised HDL C 5%. Creactive protein and Lp(a) values have already been measured. Fatal and nonfatal myocardial infarction (MI) were decreased by 19%, and fatal MI 24%, but increased risk of new cancer were noted in the pravastatin group over 3.2 years as compared to the placebo group (all p<0.01) (Lancet 360: 1623-30, 2002). Benefit was greatest in subjects with low HDL C (<1.1 lmml/L or 43 mg/dl). No benefit of pravastatin versus placebo on cognitive function or stroke was noted. We and others have shown that statins increase large alpha 1 migrating apolipoprotein A-I containing HDL, decrease plasma lathosterol, a marker of cholesterol synthesis, and increase plasma betasitosterol, a marker of cholesterol absorption as well as decrease cholesterol ester transfer protein (CETP) mass. We propose to measure HDL subspecies, CETP mass, lathosterol, and beta-sitosterol in the 292 subjects who developed CHD while on pravastatin and in a control group (n=292) who did not develop CHD on pravastatin. We propose to isolate DNA in all subjects, carry out sequencing for single nucleotide polymorphism detection in 5 male and 5 female hyper-responders and the same number of hypo-responders (LDL C <10% reduction) and then genotyping at all SNPs on the two 292 patients groups, and the informative SNP detection on the entire 5804 cohort at the following gene loci: ATP binding cassette transporters G5 and G8 (ABCG5, ABCG8), CETP; HMG CoA reductase, apolipoprotein E, lipoprotein and hepatic lipase, microsomal transfer protein, C-reactive protein, connexin, plasminogen activator type I inhibitor and stromelysin I. These genes have been selected because of our own preliminary studies, and their known key role in cholesterol absorption and lipoprotein metabolism or CHD. We hypothesize that response to pravastatin in terms of lowering of LDL C, triglycerides and C-reactive protein, and HDL C raising will be related to specific genotypes and haplotypes. We also hypothesize that subjects with the greatest LDL Cand C-reactive protein-lowering, the greatest increase in large alpha HDL particles, the greatest reduction in lathosterol and the least increase in beta-sitosterol will have the

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greatest benefit in CHD risk reduction, and that these changes will be related to specific genotypes and haplotypes of the candidate genes being examined. These results can be used to formulate guidelines for identifying elderly subjects for statin treatment to prevent future CHD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEMEOSTASIS

PHOSPHODIESTERASE

REGULATION

OF

GLUCOSE

Principal Investigator & Institution: Michaeli, Tamar H.; Developmtl & Molecular Biology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 15-MAR-2003; Project End 31-DEC-2006 Summary: (provided by applicant): The objective of the proposed research is to elucidate the contribution of the camp phosphodiesterase, PDE7A, to the regulation of glucose homeostasis. Since cAMP antagonizes insulin action, cAMP phosphodiesterases can augment insulin signaling by reducing levels of cAMP pools relevant to insulin action. In particular, PDE3B augments insulin signaling in fat and liver. PDE3B, however, is not expressed in skeletal muscle. Our studies established PDE7A as a cAMP specific phosphodiesterase expressed to high levels in skeletal muscle as the particulate PDE7A2 splice variant. Our targeted disruption of the PDE7A gene in mice yielded PDE7KO mice with defects in glucose homeostasis - glucose intolerance and insulin resistance. PDE7KO mice, however, are not hyperinsulinemic and their insulin secretion in response to injected glucose is indistinguishable from that of wild type mice. Consistent with the abundant expression of PDE7A2 in skeletal muscle, and with the strong contribution of skeletal muscle to whole body glucose disposal, PDE7KO mice are impaired in insulin stimulated glucose uptake by skeletal muscle, but not by adipose tissue. Based on these observations, we hypothesize that a primary defect in PDE7KO mice is the disposal of glucose by skeletal muscle. The experimental program will examine in vivo defects of PDE7KO mice in glucose disposal, glucose and lipid metabolism, cAMP and insulin signaling, in skeletal muscle, and in liver and adipocytes. The contribution of pancreatic beta-cells to PDE7KO phenotypes will also be assessed. Thus, the aim of the proposal is to at understand the cross talk between the insulin and the cAMP signaling pathways and mechanisms underlying diabetogenic, metabolic perturbations in glucose homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHOSPHOLIPID SYNTHESIS BY GIARDIA LAMBLIA Principal Investigator & Institution: Das, Siddhartha; Associate Professor; University of Texas El Paso El Paso, Tx 79968 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): The ancient protist, Giardia lamblia colonizes the small intestine of humans and animals. This protozoan parasite lacks mitochondria, highly evolved Golgi structures, and other organelles typical of higher eukaryotes. Nonetheless, it has developed unique metabolic pathways that allow this parasite to survive and multiply in the small intestine by scavenging lipid molecules from the host. Various investigators have shown that Giardia trophozoites are unable to synthesize the majority of their own lipids and cholesterol de novo; rather, they depend mostly on supplies from outside sources. Naturally, the questions of how they scavenge and utilize exogenous lipids for metabolic purposes are extremely important. Earlier we have shown that exogenous phospholipids, once internalized, can be remodeled via

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deacylation/reacylation and headgroup exchange reactions, which allow Giardia to alter lipids and generate parasite-specific phospho and glycophospholipid molecules. In addition, recent results from our laboratory suggest that transbilayer/ cellular movement of fluorescent-conjugated sphingolipids is dependent on actin filaments and the microtubule network, suggesting the presence of sophisticated lipid transport machinery in Giardia. The major goal of this proposal is to investigate the underlying mechanisms of lipid transport and metabolism in this early-diverging protozoan cell. Therefore, the specific aims are: Aim-1 to investigate the transbilayer lipid transport and trafficking, and the possible role of giardial actin/microtubule cytoskeleton in these processes; Aim-2 to investigate and characterize the regulatory enzyme(s) of phospholipid deacylation/reacylation reactions (i.e., phospholipase/lysophospholipase) by molecular/biochemical methodologies; Aim-3 to study the key enzymes of headgroup exchange pathways, and finally Aim-4 to test the effects of various inhibitors/analogs of lipid metabolic enzymes on in vitro growth of this water-borne pathogen. These studies will yield valuable information regarding lipid synthesis/remodeling by mucosal protozoa, and will lay the foundation for future investigations on novel chemotherapies against Giardia and other related protozoan parasites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PLEIOTROPIC EFFECTS ON OBESITY AND LIPOPROTEINS Principal Investigator & Institution: Comuzzie, Anthony G.; Associate Scientist; Southwest Foundation for Biomedical Res San Antonio, Tx 782450549 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: Obesity is an important risk factor for atherosclerosis. However, the reasons for the relationship between these disorders are still poorly understood. Evidence from body composition studies suggests that adiposity is highly correlated with several important endocrine measures including phenotypes related to glucose and lipoprotein metabolism. Little is known regarding the genes that influence adiposity and their pleiotropic effects on these endocrine parameters and on correlated risk factors for atherosclerosis such as lipoprotein phenotypes. In this Project, we will measure several adiposity-related phenotypes including total body fat (estimated using bioimpedance), and serum concentrations of several adipocyte derived endocrine factors (e.g., leptin, adiponectin, acylation stimulating protein, and TNFalpha) in pedigreed baboons. To better examine the underlying genetic determinants of variable gene expression, we will also continue to measure quantitative mRNA levels of several candidate genes (the leptin, lipoprotein lipase, and glucose transporter 4 genes) as well as three additional genes (the leptin receptor, adiponectin, and resistin genes) in biopsied omental fat tissue. We will detect and localize quantitative trait loci (QTLs) influencing adiposityrelated phenotypes and test hypotheses regarding their pleiotropic effects on lipoprotein traits and genotype ? age interaction. Localization of quantitative trait loci will be accomplished via a genomic screen using candidate gene and STR polymorphisms in a single pedigree of 750 non-inbred baboons. Statistical linkage analyses will be performed using the multipoint variance component method which makes efficient use of all available information and which we have extended to accommodate the complications of inbred pedigrees. When a quantitative trait locus is found, we will utilize multivariate linkage analysis to determine if adiposity-related genes have pleiotropic effects on lipoprotein phenotypes. Finally we will attempt to identify strong positional candidate genes in the regions of promising QTLs and will use combined linkage/disequilibrium analyses and a novel Bayesian quantitative trait nucleotide

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analysis method to assess whether polymorphisms in these genes account for the observed linkage signal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POLYMORPHISMS OF B1 AND B2 RECEPTOR GENES AND OBESITY Principal Investigator & Institution: Lima, John J.; Professor; Nemours Children's Clinic 807 Children's Way Jacksonville, Fl 322078482 Timing: Fiscal Year 2002; Project Start 15-JUN-2001; Project End 31-MAY-2004 Summary: Obesity has been associated with insulin resistance, hyperinsulinemia, noninsulin-dependent diabetes mellitus, hypertension and a higher risk of cardiovascular disease and death. Genetic, metabolic and environmental factors are known to contribute to obesity. Genes that are involved in the regulation of catecholamine function may be important because of the role catecholamines play in energy expenditure and lipolysis. Ninety percent of fat in the body is stored in white adipose tissue as triglycerides, which are broken to free fatty acids and glycerol through the action of hormone-sensitive lipase. Lipolysis is stimulated by beta1, beta2 and beta3 adrenergic receptors in human adipocytes, with the beta1 and beta2 adrenergic receptors (beta1 and beta2 AR) being the most dominant subtypes. Catecholaminestimulated lipolysis is reduced in obesity, which is thought to be due to defects in the beta2 AR-signaling pathway. Mis-sense mutations in the beta1 AR gene results in polymorphisms at nucleic acid 145 (A->G), which results in a substitution of Ser for Gly at position 49, and at nucleic acid 1165 (G- >C, which results in a substitution of Gly for Arg and position 389. Beta1 AR polymorphisms have functional significance; whether or not they associate with obesity is unknown. Mutations in the 5' leader and coding regions of the human beta2 AR gene give rise to several polymorphisms, which can after receptor density and function. The working hypotheses of this submission are that polymorphisms at position 389 and haplotypes of beta2 AR polymorphisms in the 5' leader and coding regions associate with obesity. Specific Aim #1: to compare the beta1 AR allele frequencies and genotypes in healthy obese and non- obese subjects. The hypothesis driving this specific aim is that obesity associates with the Gly 389 beta1 AR allele. Specific Aims #2: to compare the distribution of beta2 AR haplotypes in healthy obese (Body Mass Indexes > 30) and non-obese (BMI < 25) subjects. Beta2 AR haplotypes will be determined by PCR and direct sequencing. The thesis driving this specific aim is that obesity associates with the Arg19-Gly16- Glu27 beta2 AR haplotype. The distribution of beta2 AR haplotypes in 118 non-obese and 118 otherwise healthy obese subjects will be compared. The results of this study will determine whether polymorphisms in beta1 and beta2 AR allels associate with obesity. The information obtained from our studies are important in designing clinical trials of interventions designed to reduce body weight. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POSTPRANDIAL VITAMIN A Principal Investigator & Institution: Blaner, William S.; Professor; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2004; Project Start 01-AUG-2004; Project End 30-JUN-2009 Summary: (provided by applicant): Dietary vitamin A is absorbed in the intestine where it is converted to retinyl ester. This retinyl ester is packaged along with other dietary lipids into nascent chylomicrons and secreted into the lymphatic system. Upon entering

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the general circulation the chyiomicrons undergo metabolism that gives dse to chylomicron remnants that are cleared from the circulation by liver and other tissues. Approximately 66-75% of chylomicron remnant retinyl ester is taken up by the liver where it is either resecreted into the circulation as retinol bound to retinol-binding protein (RBP) or stored in hepatic stellate cells. The remaining postprandial vitamin A is cleared by extrahepatic tissues. At present, there is only very limited understanding of the biochemistry that underlies the uptake and processing of postprandial vitamin A, either by the liver or by other tissues. Our studies will provide new biochemical understanding of these processes. We are proposing to identify factors and to investigate mechanisms responsible for the uptake and processing of postprandial vitamin A within the liver and in extrahepatic tissues, especially focusing on heart and mammary tissue. All of our studies will be carried out in knockout and transgenic mice. In Aim 1, we propose to investigate how chylomicron remnant retinyl ester is taken up by hepatocytes and how the newly absorbed vitamin A is transferred from hepatocytes to hepatic stellate cells for storage. We will investigate the roles that RBP and cellular retinol-binding protein, type I (CRBPI) have in this process. Uptake of postprandial vitamin A into the heart will be examined in Aim 2. Unlike the liver, the heart does not store vitamin A. However, the heart has a relatively high need for retinoic acid for maintaining cellular health. In Aim 2, we will examine the roles that RBP and cellular retinol-binding protein, type III (CRBPIII) have in facilitating cardiac retinoic acid synthesis from postprandial vitamin A and in retinol resecretion from the heart. In Aim 3 we plan to explore how postprandial vitamin A is taken up and processed by mammary tissue for incorporation into milk. Our preliminary data indicate that postprandial vitamin A is an important source of the vitamin A present in milk. Here, we will focus on the roles that RBP, CRBPI, CRBPIII and lipoprotein lipase have in facilitating postprandial vitamin A incorporation into milk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PPAR-GAMMA REDISTRIBUTION

AGONISTS,

WEIGHT

GAIN

AND

FAT

Principal Investigator & Institution: Johnson, Julia A.; St. Luke's-Roosevelt Inst for Hlth Scis New York, Ny 10019 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 30-NOV-2005 Summary: (provided by applicant): The candidate for this Research Career Award (K01) plans through this application to receive additional training in conducting animal and clinical research, with a special emphasis in learning cell and molecular biology techniques commonly employed in studying adipocyte biology. Her ultimate goal is to attain independent funding to continue her research in adipose tissue metabolism and development as it relates to obesity and the metabolic syndrome. The New York Obesity Research Center is well-equipped to offer her further instruction and training in these areas. Thiazolidinediones, drugs commonly used in the treatment of type 2 diabetes mellitus, improve insulin sensitivity and hyperlipidemia partly through inducing repartitioning of lipid towards adipose tissue storage. These drugs are ligands for the transcription factor peroxisome proliferator activated receptor gamma (PPAR gamma), which is a regulator of adipocyte differentiation. Weight gain is a common side effect of these drugs, but it is unclear which individuals are most susceptible to gaining weight during treatment. These PPAR gamma agonists also have been shown to redistribute adipose tissue from visceral to subcutaneous compartments in type 2 diabetic subjects. It is not known which PPAR gamma agonist-induced changes in adipose tissue metabolism are responsible for the fat redistribution and improvement in insulin

50

Lipase

sensitivity. The Specific Aims of this application are as follows: (1) To determine changes in adipose tissue metabolism and respiratory quotient that accompany PPAR gamma agonist-mediated increased insulin sensitivity in nondiabetic obese insulinresistant human subjects. (2) To examine regional variation in PPAR gamma agonistmediated effects in vitro on metabolism and gene expression, in different subcutaneous abdominal and visceral fat depots from morbidly obese human subjects. (3) To examine whether PPAR gamma agonists mediate changes in adipose tissue that may alter susceptibility to weight gain in rodents when exposed to a high fat diet, post-treatment. The results of these studies will assist physicians in predicting which patients will best respond to thiazolidinedione therapy, and will help to develop strategies to minimize weight gain during and after treatment with PPAR gamma agonists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PRENATAL EXPOSURES AND PREECLAMPSIA PREVENTION Principal Investigator & Institution: Roberts, James M.; Director, Magee-Womens Research Institut; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: In this proposal we test the role of oxidative stress in the pathophysiology of preeclampsia. Oxidative stress generates free radicals that injure tissues, especially vascular endothelial cell function as components of oxidized LDL (ox-LDL), alter endothelial cell structure and function. Data from our lab and others support alterations of endothelial cell function as a component of the pathophysiology of preeclampsia. In addition, preliminary data from our group indicates potential generation of pro oxidants by preeclamptic placenta. We demonstrated increased xanthine oxidase/dehydrogenase, an enzyme which can generate superoxide, in invasive cytotrophoblast from preeclamptic women. We recently demonstrated material in the blood or plasma of preeclamptic women that increases ascorbate oxidation in vitro. We propose to characterize the activity. Whether these findings indicate cause or effect or are an epiphenomenon cannot be answered by available data. We propose definitively testing a causal role. We will study circulating markers of oxidative stress before, during and after preeclampsia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTEASE INHIBITOR RELATED ADIPOGENESIS IN HIV INFECTION Principal Investigator & Institution: Agrawal, Krishna C.; Regents Professor and Chairperson; Pharmacology; Tulane University of Louisiana New Orleans, La New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-MAY-2004 Summary: (Provided by applicant) The clinical use of HIV-1 protease inhibitors (PIs) in highly active anti-retroviral therapy (HART) has led to significant improvements in the prognosis and quality of life in HIV-1 infected patients. However, long-term use of PIs has resulted in side effects such as peripheral lipodystrophy, hyperlipidemia, insulin resistance, and disruption of the adipogenic process. Our preliminary studies have shown that PIs suppress adipogenic differentiation in 3T3-L1 cells and the addition of TNFalpha further suppressed the rate of adipogenesis. In contrast, the insulin sensitizing agent, troglitazone, blocked this suppression even in TNFalpha sensitized cells. The primary goal of the proposed research is to investigate the molecular

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mechanisms involved in the PI-induced modulation of adipogenesis and to test the hypothesis that preadipocytes are sensitized by HIV-1 induced inflammatory cytokine TNFalpha and/or HIV-1 Tat protein, to PI-induced disruption of adipogenesis. This will be achieved by the following specific aims: 1.) To determine the in vitro effects of PIs on adipogenic differentiation in human bone marrow stromal progenitor cells. Transcripts of early, middle and late genetic markers i.e., pref-1, lipoprotein lipase (LPL) and GAPDH, respectively will be determined. Levels of nuclear transcription factors, PPARgamma and C/EBP-alpha will be determined by transient transfection assays and gel mobility shift assays. 2.) to determine the sensitizing effect of the HIV-1 induced inflammatory cytokine, TNFalpha and/or HIV-1 Tat protein on PI-induced inhibition of adipogenic differentiation in human bone marrow stromal progenitor cells. 3.) To determine the in vitro effects of PIs on the activity of ECM degrading proteases in human stromal adipogenic progenitor cells. Fibrinolytic activity in undifferentiated and differentiated cells will be monitored by using a chromogenic plasmin substrate. The ECM production at different stages of differentiation will be determined by SDS-PAGE electrophoresis and the activation of ECM degrading proteolytic enzymes (MMPs) will be monitored by gelatin zymography. Real time RT-PCR studies will monitor gene expression of tPA, PAI-1/2 and MMPs/TIMPs which are involved in the fibrinolytic cascade. 4.) To investigate the ameliorative effects of insulin sensitizers on PI-induced lipodystrophy. We will investigate the efficacy of thiazolidinediones (rosiglitazone and pioglitazone) and biguanides (metformin) in suppressing the effects of PI-induced inhibition of adipogenic differentiation. These studies will delineate the molecular mechanisms that may be responsible for the adipogenic side effects induced by the PIs in the presence of HIV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF CYTIDYLYTRANSFERASE IN FETAL RAT LUNG Principal Investigator & Institution: Mallampalli, Rama K.; Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 31-DEC-2005 Summary: (provided by applicant): Surfactant deficiency plays an integral role in the pathogenesis of neonatal lung diseases such as RDS and acute lung injury. Although surfactant replacement therapy has made an impact in RDS, it is not totally effective. An alternative strategy to increase the alveolar surfactant pool is by stimulating biosynthesis. Surfactant synthesis is tightly controlled by the rate-limiting enzyme, cytidylyltransferase (CT). CT activity is inhibited by sphingolipids and stimulated by fatty acids. However, prior studies administering fatty acids in vivo to stimulate surfactant production have had mixed success with associated toxicity. Thus, the goal of this proposal is to develop a novel and safe approach to stimulating surfactant synthesis in fetal lung by the use of very low density lipoproteins (VLDL) and lipoprotein lipase (LPL). This revised competing renewal expands from recent advances in our laboratory made through support of the existing grant showing that 1) fatty acids carried within very low density lipoproteins (VLDL) are potent stimulators of CT activity in vitro in the presence of LPL and 2) oxidized lipoproteins inhibit surfactant synthesis,. These observations led to the hypothesis that native lipoprotein loading and oxidized lipoproteins differentially regulate the CT enzyme. We will investigate whether loading with native lipoproteins (VLDL) increases CT activity by altering fatty acids and sphingolipids associated with the enzyme (AIM 1). We will also investigate how modified (oxidized) lipoproteins acutely down-regulate surfactant synthesis by inducing CT proteolysis (AIM 2). Our hypothesis will be tested, in vivo, by maternal

52

Lipase

administration of lipoproteins in pregnant rats and with analysis conducted in primary fetal type II cells. These in vivo studies will be supplemented with use of a lipoproteinresponsive type II (MLE12) cell line. The unique contributions of this proposal impacting the field of surfactant metabolism include: 1) mechanistic studies with potential clinical application by which native lipoproteins control CT function posttranslationally (AIM 1) and 2) studies investigating CT regulation at the level of protein stability (AIM 2). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF EPITHELIAL CELL MOTILITY BY VILLIN Principal Investigator & Institution: Khurana, Seema; Associate Professor; Physiology; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): The PI proposes to determine and characterize the role of villin and its ligands (phosphatidylinositol 4,5- bisphosphate (PIP2) and actin) in epithelial cell motility. Active cell motility regulates many important intestinal epithelial cell functions, including: ion transport proteins via endocytosis and exocytosis, crucial for absorption of nutrients; intestinal restitution, important to maintain homeostasis in the presence of large osmotic and mechanical stress; the movement of cells along the crypt-villus axis; the invasion and propagation of enteropathogens; immune surveillance and inflammation; as well as neoplastic tumor cell dissemination and metastasis. Villin is an actin nucleating, capping, severing, and bundling protein. Villin binds and regulates two ligands that are known to regulate cell motility, phospholipase C-gamma1 (PLC-gamma1) as well as the substrate of the lipase namely, phosphatidylinositol 4,5-bisphosphate (PIP2). Recent studies with villin knock out mice have demonstrated that villin is necessary to regulate epithelial cell motility. In addition, villin shares sequence homology with other proteins of its family including gelsolin, which have been shown to regulate cell motility in vivo. Our working hypothesis is that villin's ability to regulate phosphoinositide-mediated signal transduction pathways and the actin cytoskeleton is important to epithelial cell physiology and pathophysiology involving changes in cell motility. To accomplish our overall study objectives we will characterize the villin-PIP2 interaction using the following approaches: reconstitution in vitro using recombinant villin proteins; endogenous villin expression in the intestinal epithelial cell line, Caco-2; and over expression of villin and enzymes that regulate intracellular PIP2 levels, in the villin null intestinal cell line, IEC-6 using a tetracyclineregulated system. To determine unequivocally the role of villin in the epithelial cell motility, we will use villin knock out mice. These studies promise the prospect of modifying motility for enhancement of normal physiology and for amelioration of disease. Inhibition of epithelial cell motility can be significant in several diseases, including inflammatory bowel disease, celiac disease, and colon cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF LIPOPROTEIN LIPASE IN ADIPOCYTES Principal Investigator & Institution: Kern, Phillip A.; Professor; Internal Medicine; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 01-SEP-1988; Project End 30-JUN-2006 Summary: (Scanned from the Applicant's Description): Lipoprotein lipase (LPL) is a central enzyme in lipid metabolism and adipocyte biology. Although the changes in LPL activity with diabetes and other conditions have been well described, the mechanism of

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LPL regulation is complex. We have described regulation of LPL translation in response to catecholamines, thyroid hormone, and in diabetes. Our recent studies have described an RNA binding protein that inhibited translation through binding to the 3'UTR of the LPL mRNA. We have now identified a member of the RNA binding complex as the alpha catalytic subunit of cAMP dependent protein kinase (PKA). In addition, we have produced transgenic mice that express an LPL gene (LPLt) that lacks the RNA binding motif on the 3'UTR. Our future aims are to better characterize the role of PKA in LPL regulation, and to better understand the role of translation in the physiologic regulation of LPL. Hypothesis 1. Protein kinase A (PKA) is involved in the translational regulation of LPL. Aim 1. Characterize the binding of the PKA C subunit to LPL mRNA: tissue specificity and involvement of other proteins. Aim 2. Determine the sequence and kinase activity of the C subunit involved in translational regulation. Aim 3. Characterize the motif on the 3'UTR of LPL that is involved in C binding. Aim 4. Determine whether LPL translation is altered in PKA knockout mice. Hypothesis 2. Regulation of LPL translation is important physiologically. Aim 1. Examine the translational regulation of both LPLt and wild type LPL (LPLwt) in response to epinephrine, thyroid hormone, and phorbol ester in isolated adipocytes from transgenic mice. Aim 2. Examine the regulation of LPLt and LPLwt in adipose tissue of transgenic mice following the induction of streptozotocin-diabetes or hypothyroidism, and the in vivo administration of epinephrine. Aim 3. Examine the mechanism by which the expression of LPLt in transgenic mice is accompanied by a down regulation of wild type LPL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESOLUTIONS IN BRANCHED ALKANES USING LIPASE IN BEADS Principal Investigator & Institution: Neau, Steven H.; Pharmaceutical Sciences; University of Missouri Kansas City Kansas City, Mo 64110 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The long-term goals of this research are to investigate and characterize fresh and freeze-dried macromolecule-loaded polysaccharide-based hydrogel beads for applications in chemical reactions, and their application in macromolecule delivery for therapeutic purposes. The use of these beads for therapeutic peptide and protein delivery will be pursued, in particular for site specific delivery of these agents to the colon following oral administration. Various chemical reactions can be investigated using entrapped enzymes. The long-term goals include applications of these beads in reactions where the catalysis is well characterized, such that the bead performance (and not the reaction) is studied. The proposed research incorporates lipase into these beads for easy recovery and subsequent delivery. The solvents are straight chain and methyl-branched alkanes to test the hypothesis that branching can enhance the activity and enantioselectivity of lipase. The short-term goal is the resolution of the pharmacologically active enantiomer of a drug that is a racemic mixture, ibuprofen, by enantioselective esterification by a lipase that is free or entrapped in the chitosan bead. Isolation of the active, enantiomer will become a regulatory requirement because administration of only the active enantiomer can reduce the toxicity and dose. Resolution using an entrapped lipase offers a rapid, enantioselective reaction; repeated applications since the enzyme can be recovered; and economical terminal resolution in the synthesis sequence. In the first study, the solvent system, consisting of water at a known activity in an alkane, will be optimized for the fastest reactions and the highest enantioselectivity. Michaelis-Menten parameters will be evaluated and compared. In the second study, lipase-loaded chitosan hydrogel beads

54

Lipase

are fabricated. The successful rugged, spherical matrix can entrap the enzyme, minimally interfere with activity, and allow substrate and product diffusion. Permeability of the bead will be investigated by measuring the substrate diffusion coefficient within the bead. Reaction parameters of the entrapped enzyme will be compared to those of the free enzyme in the third study. The stability of the bead, the efficiency of the lipase entrapment, and the reduction in lipase activity as a function of repeated applications will also be evaluated in the third study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RETINOID METABOLISM IN HEPATITIC STELLATE CELLS Principal Investigator & Institution: Bosron, William F.; Professor; Biochem and Molecular Biology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-JUL-2006 Summary: (provided by applicant): The overall goal of this proposal is to understand the role of specific rat retinoid metabolizing enzymes (especially retinyl ester hydrolases) in the regulation of retinoid metabolism in hepatic stellate cells. Hepatic stellate cells are the main reservoir of Vitamin A in the liver where it is stored mainly as retinyl palmitate in highly visible intracellular lipid droplets. When animals are exposed to hepatotoxins or humans chronically abuse alcohol, the stellate cells become activated and transform into myofibroblast-like cells. These transformed cells are the sites of collagen and extracellular matrix protein formation in alcohol-induced hepatic fibrosis. One of the earliest events in stellate cell activation is the hydrolysis of retinyl esters and the depletion of the intracellular lipid droplets. The most likely retinyl ester hydrolase candidates are the members of the families of broad substrate specificity lipases and carboxylesterases. The specific retinyl ester hydrolases expressed in hepatic stellate cells and the mechanisms for regulation of their activity during stellate cell activation is not known. In preliminary data, we show that the five most common rat liver carboxylesterases with retinyl palmitate activity are not highly expressed in stellate cells. However, the hormone-sensitive lipase gene is expressed in rat hepatic stellate cells and it has retinyl palmitate hydrolase activity in vitro. The goals of the grant are to identify the specific retinyl ester hydrolases (lipases and carboxylesterases) that are expressed in isolated rat liver cells (stellate cells, Kupffer cells, hepatocytes) by real-time, quantitative PCR of RNA and immunofluorescence microscopy of stellate cells with enzyme-specific antibodies. The expression of retinyl ester hydrolases and retinol dehydrogenases will be correlated with retinoid autofluorescence in lipid droplets and expression of cellspecific markers in cultured rat stellate cells as they undergo activation to myofibroblast-like cells. When feasible, we will measure retinyl palmitate hydrolase activity and perform protein gel electrophoresis of cellular extracts with esterase activity staining. We will examine the kinetics of purified rat stellate cell retinyl ester hydrolases and examine the effects of enzyme activators and inhibitors. Inhibitors of retinyl ester hydrolysis in stellate cells may be an effective therapeutic strategy for arresting stellate cell activation early in hepatic fibrosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE DEGENERATION

OF

CHOLESTEROL

HOMEOSTASIS

IN

MACULAR

Principal Investigator & Institution: Lakkaraju, Aparna; Ophthalmology; Weill Medical College of Cornell Univ New York, Ny 10021

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55

Timing: Fiscal Year 2003; Project Start 01-DEC-2003; Project End 30-NOV-2005 Summary: (provided by applicant): The main objective of this proposal is to investigate the role of cholesterol homeostasis in the pathogenesis of age-related macular degeneration. Although several reports suggest that aberrant cholesterol metabolism may play a role in AMD pathogenesis, the underlying cell biology of this process is unclear. Published work from our laboratory demonstrates that the lipofuscin component A2E delays the degradation of rod outer segment lipids in retinal pigment epithelial (RPE) cells without affecting protein processing. The first specific aim of this proposal will extend this work by investigating the mechanistic aspects of A2E-induced phospholipid and cholesterol accumulation in the RPE. Lysosomal lipase activities, transcriptional activation and enzyme-substrate interactions will be studied in the presence and absence of A2E. The second specific aim will examine the roles of the LDL receptor, the scavenger receptor class B type l, caveolin-1 and the ATP-binding cassette transporter A1 in polarized lipoprotein internalization and cholesterol/phospholipid efflux pathways in the RPE and investigate how A2E affects these processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF SPHINGOMYELIN IN LIPOPROTEIN METABOLISM Principal Investigator & Institution: Subbaiah, Papasani V.; Professor; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The long term objective of this proposal is to investigate the physiological role of sphingomyeIin (SPH) in plasma, where it is the most abundant phospholipid next to phosphatidylcholine (PC). In contrast to its functions in membrane cholesterol metabolism and signal transduction, the role of SPH in the metabolism of plasma lipoproteins has received little attention, although its concentration is significantly increased in atherosclerosis and aging. Based on preliminary data, the PI proposes that SPH modulates plasma lipolytic activities, reverse cholesterol transport pathways, and lipid peroxidation reactions, thereby preventing excessive turnover and premature degradation of PC and cholesterol.The PI will test the hypothesis that SPH, by virtue of its structural similarities to PC, competitively inhibits not only LCAT, as he previously showed, but also other lipolytic enzymes that hydrolyze PC, such as hepatic lipase and secretory phospholipases A2. He will also investigate the mechanism(s) involved in the inhibition of these activities, by employing monolayer techniques, enzyme kinetics, and structural modifications of the SPH molecule. The role of SPH in the exchange of free cholesterol and cholesteryl ester (CE) between lipoproteins, and in the selective uptake of HDL CE by various cells in culture will be studied by manipulating the SPH concentration of native lipoproteins and recombinant HDL (rHDL) particles. Since the surface concentration of CE determines its transfer rate, the effect of SPH on the partitioning of CE into surface lipids of rHDL will be investigated by [13C] NMR. The possible role of membrane SPH in the function of SR-B1 receptor will also be investigated.The PI proposes to test the novel hypothesis that SPH inhibits lipid peroxidation by retarding the propagation of lipid peroxy radicals and that the increased oxidative susceptibility of small dense LDL, compared to buoyant LDL, is due to the low SPH/PC ratio in the former. He will correlate the oxidizability of various LDL subfractions and synthetic liposomes with their SPH/PC ratios. The mechanism by which SPH inhibits lipid peroxidation will be investigated by using structural analogs of SPH, by oxidizing fluorescent probes which are specifically localized in the surface or core of lipoproteins, and by studying the effects of SPH on membrane fluidity and lateral diffusion rates.The results from these studies should

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provide new insights into the physiological functions of SPH in lipoproteins, and its possible relevance to atherosclerosis and inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SECRETION AND BIOSYNTHESIS OF INSULIN Principal Investigator & Institution: Mcdaniel, Michael L.; Professor; Pathology and Immunology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-MAY-1977; Project End 31-JAN-2007 Summary: (provided by applicant) Type 2 diabetes is associated with obesity and elevated plasma levels of free fatty acids (FFA) and triacylglycerides (TAG). Obesity is also associated with the development of insulin resistance in insulin-sensitive tissues that results in hyperglycemia and hyperinsulinemia. b-cell failure in obesity-associated type 2 diabetes is believed to correlate with the intracellular accumulation of lipids that contribute to defects in insulin secretion and/or insulin and growth factor signaling necessary to maintain sufficient b-ceIl mass. The overall goal of this proposal is to define the cellular mechanisms whereby FFA and TAG exert their inhibitory effects on b-cell function in obesity-associated type 2 diabetes. Our recent studies have identified lipoprotein lipase (LpL) in b-cells, a key enzyme for catalyzing the hydrolysis of lipoprotein-associated TAG, to produce FFA for local cellular uptake. Our overall hypothesis is that LpL serves as a gatekeeper for the physiological import of FFA into bcells analogous to that described for adipocytes. Furthermore, our new findings indicate that elevated concentrations of glucose and insulin enhance LpL enzyme activity in bcells that may explain how b-cells continue to accumulate lipids in the setting of hyperglycemia and hyperinsulinemia associated with type 2 diabetes. In specific aim 1, we will: 1) further characterize the ability of nutrients, glucose and amino acids, and insulin to regulate LpL activity, expression and intracellular localization in rodent and human islets and b-cell lines, 2) assess the role of rapamycin, an inhibitor of mTOR, to regulate LpL and: lipid levels, and 3) evaluate LpL function in vivo. In specific aim 2, we will 1) examine the effects of enhanced FFA uptake by overexpression of FATP1 and ACS1, 2) characterize lipid droplet associated proteins, ADRP, perilipins and HSL, and 3) determine the regulation of lipid droplet synthesis and breakdown by phosphorylation and overexpression of lipid droplet associated proteins. Mitochondria exert a major role in glucose-stimulated insulin secretion, and mitochondrial activation is required for normal signal transduction. Recent studies suggest that FFA up-regulate mitochondrial uncoupling proteins (UCP) proposed to dissipate the proton gradient across the mitochondrial inner membrane. In specific aim 3, we will: 1) determine the role of UCP in mediating b-cell function by overexpressing UCP-2 in islets and b-cell lines, 2) assess the modulation of UCP-2 by increased levels of FFA in vitro and in vivo as described in specific aims 1 and 2. This experimental approach will be used to delineate the link between FFA and b-cell mitochondrial dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SELECTIVE UPTAKE FROM LDL:ROLE OF THE PLASMA MEMBRANE Principal Investigator & Institution: Seo, Toru; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-DEC-2004 Summary: (provided by applicant) The applicant's long-term goal is to determine the cholesterol delivery mechanisms and their regulation. Cholesterol delivery to cells and

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tissues is a critical process in maintaining normal cell function. Specifically, regulatory roles of free cholesterol (FC) and free fatty acids (FFA) on cholesterol delivery have been of interest since they affect cell lipid metabolism at various levels; influx and efflux of lipoproteins as well as direct effects on cell receptors and lipogenic processes at genetic levels. The proposed studies will examine selective uptake (SU) as a mechanism for cell cholesterol delivery and its regulation by FC and FFA, and will allow the applicant to expand his research competition. New techniques such as fluorescent microscopy and use and generation of transgenic mice used in studies herein will provide new skills for future studies. Our previous studies demonstrated that J774 macrophages incubated with FFA increased not only LDL uptake by the LDL receptor (LDLR), but also markedly stimulated SU of cholesteryl esters (CE) from LDL. Although LDL uptake via LDLR is a primary cholesterol delivery pathway, other pathways such as SU are important in cells and tissues with little or no LDLR. Since an initial step of SU likely involves the CE transfer to the plasma membrane, the role of the plasma membrane, particularly FC and sphingolipid rich membrane rafts, as a CE acceptor will be determined by assessing transfer of (3H) cholesteryl ethers from LDL core to isolated membranes or large unilamellar vesicle (LUV) as model membranes. Moreover, since FC modulates membrane fluidity, changes in FC content in membranes on CE transfer from LDL will be examined (Aim 1). Similarly, potential roles of FFA on regulating SU will be examined by directly intercalating various FFA, or altering phospholipid content in the plasma membrane that occurs in cells incubated with FFA (Aim 2). The second step of SU, internalization of membrane CE, will be addressed by using fluorescently labeled LDL, where LDL-CE and apolipoprotein B (apoB) will be traced with fluorescent BODIPY and ALEXA, respectively. Studies will be performed to determine what cell organelles are required for CE internalization by disrupting various cell organelles with specific inhibitors. We will determine whether membrane rafts are required for CE internalization and whether FFA affect raft-mediated CE trafficking by in situ colocalization of CE and membrane rafts in the presence or absence of FFA. Also, two different SU pathways, mediated by lipoprotein lipase vs. FFA, will be compared to determine whether CE internalization by these pathways are different (Aim 3). Finally, the physiological relevance of LDL SU in tissues will be determined using mutant mice and whether dietary intakes of different fats modulate cholesterol delivery to tissues via SU from LDL and whether macrophage specific expression of LpL stimulates cholesterol delivery to extrahepatic tissues (Aim 4). Roles of SU and its regulation by FC and FFA will be delineated and results from these studies will provide further understanding on mechanisms of cholesterol delivery to cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE-FUNCTION ANALYSIS OF COLIPASE AND LIPASE Principal Investigator & Institution: Lowe, Mark E.; Professor of Pediatrics and Director; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 31-MAR-2006 Summary: The long-term goal of this project is to describe the biochemical mechanisms of the lipolytic enzymes responsible for dietary fat digestion. Dietary fats provide a major source of energy, essential fatty acids, a vehicle for fat-soluble vitamins, and components of cellular membranes. Fats eaten in excess adversely affect health increasing the risk of cardiovascular disease and obesity. Before fats can be absorbed, they must be digested. Lipases in the stomach and duodenum digest dietary fats. This proposal focuses on the lipase responsible for the majority of fat digestion, pancreatic triglyceride lipase, and another pancreatic protein, colipase, which is required, by

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pancreatic triglyceride lipase for activity. We propose that specific interactions among lipase, colipase, lipids, and bile salts, which are necessary for absorption of the fatty acids released by lipase, dictate the function of pancreatic triglyceride lipase. The first specific aim is to characterize the mechanisms that mediate specific interactions among lipase, colipase, bile salts, and lipids. We will substitute selected amino acids in lipase or colipase by site-specific mutagenesis to identify functionally important regions of both proteins. The second specific aim is to determine the mechanisms that trigger the conversion of lipase from an inactive to an active conformation. In aqueous solution lipase is inactive. When lipase encounters the lipid substrate its conformation changes and it becomes active. We will follow the conformational change by tryptophan fluorescence to determine the factors that influence this critical conformational change. The last specific aim is to develop an expression system for labeling recombinant colipase with stable isotopes. The ability to label colipase with stable isotopes will enable NMR studies of the conformation of colipase in aqueous solutions under different conditions. We will test various culture conditions to improve our current system for the production of 15N labeled colipase and we will develop a system for economically labeling colipase with 13C and 15N. These studies will determine the biochemical details of the interactions between lipase, colipase, lipids, and bile salts that impact lipase function. The results will ultimately permit us to manipulate these interactions for therapeutic purposes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STUDIES OF REGIONAL FAT DISTRIBUTION AND ENERGY BALANCE Principal Investigator & Institution: Weigle, David S.; Associate Professor of Medicine; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 31-JAN-2006 Summary: The studies in this application are designed to better understand the regulation of body fat mass and the mechanisms determining body fat distribution in humans. Three Specific Aims are proposed: 1. To determine whether experimentallyinduced or spontaneous variations in plasma leptin levels predict subsequent changes in body composition. The protocols employed will also elucidate the mechanism by which high carbohydrate diets induce satiety and weight loss, and the mechanism of involuntary weight loss in the elderly. 2. To examine the relationships among central body fat redistribution, changes in adipogenic gene expression, and atherogenic changes in plasma lipids and insulin sensitivity. The model for this work will be the body fat redistribution that occurs in subjects receiving aggressive antiretroviral therapy for HIV infection. 3. To determine whether changes in uncoupling protein (UCP) gene expression act to attenuate diet-induced changes in body fat mass. This study will use the technology developed for Specific Aim 2 to ascertain whether muscle and fat UCP expression change in parallel with energy expenditure following experimental weight gain and weight loss in human subjects. The applicant has successfully trained several young physician investigators in patient-oriented and basic research, and a plan to continue doing so is presented. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDY OF THE DYNAMIC BINDING, STRUCTURE-FUNCTION OF CIII Principal Investigator & Institution: Breyer, Emelita D.; Chemistry; Georgia State University University Plaza Atlanta, Ga 30303

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Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Recent study shows that Apolipoprotein CIII (CIII) specifically binds and inhibits Lipoprotein Lipase (LpL) and Hepatic Lipase (HL) enzymes. The significance of the N-terminal domain in stabilizing the lipid-protein interaction and displacing Apolipoprotein E (E) was also identified (1). Our previous study that confirms the ability of CIII to displace E (2), sets up the stage for further structure-function studies evaluating the factors that enable CIII to displace E, and inhibits both HL and LpL. These functions should be investigated in correlation to CIIl's ability to bind to the lipoprotein particle (Lp) with varying size and composition. The cooperative and complex conformational modification of CIII binding to Lp and LpL/HL suggests that this study requires a factorial design experiment that can extract latent variable (factors) from collinear measurements of the protein's physico-chemical properties and structure (X-matrix), and relate these factors to the extracted latent variables from the Y-matrix consisting of the protein's functions. This study will be the first attempt to evaluate the structural factors in CIII that is responsible for the above functions in a systematic way using a factorial designed experiments. By using our model structure of CIII generated by homology with E crystal structure followed by molecular mechanics modeling, we are able to identify significant residues in CIII that may give us information regarding the difference in its function with respect to E and CII. Structural factors such as helix length, positive helix cap, loop flexibility, and hydrophobicity of side chains will be evaluated using different constructs in order to assess their contribution to the different functions of CIII. This approach is designed to give us a surface plot describing how the structural factors of CIII correlate with its functions. A more structured search and prediction of Clll analog that has a high lipid binding ability but with lipase inhibitory sites replaced by either the activating site of CII or E can be made using this approach. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF HEPATIC LIPASE IN CHOLESTEROL HOMEOSTATIS Principal Investigator & Institution: Dichek, Helen L.; Pediatrics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; 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 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

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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

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 “lipase” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for lipase in the PubMed Central database: •

A BglII RFLP at the lipoprotein lipase gene. by Hegele RA, Nakamura Y, Emi M, Lalouel JM, White R.; 1989 Nov 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=335091

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A Cold-Adapted Lipase of an Alaskan Psychrotroph, Pseudomonas sp. Strain B11-1: Gene Cloning and Enzyme Purification and Characterization. by Choo DW, Kurihara T, Suzuki T, Soda K, Esaki N.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106070

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A hepatic lipase (LIPC) allele associated with high plasma concentrations of high density lipoprotein cholesterol. by Guerra R, Wang J, Grundy SM, Cohen JC.; 1997 Apr 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20757

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A Lipase Isolated from the Silkworm Bombyx mori Shows Antiviral Activity against Nucleopolyhedrovirus. by Ponnuvel KM, Nakazawa H, Furukawa S, Asaoka A, Ishibashi J, Tanaka H, Yamakawa M.; 2003 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=228431

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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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A missense mutation at codon 188 of the human lipoprotein lipase gene is a frequent cause of lipoprotein lipase deficiency in persons of different ancestries. by Monsalve MV, Henderson H, Roederer G, Julien P, Deeb S, Kastelein JJ, Peritz L, Devlin R, Bruin T, Murthy MR, et al.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296787

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A Mutation in the Promoter of the Lipoprotein Lipase (LPL) Gene in a Patient with Familial Combined Hyperlipidemia and Low LPL Activity. by Yang W, Nevin DN, Peng R, Brunzell JD, Deeb SS.; 1995 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41964

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A silencer element for the lipoprotein lipase gene promoter and cognate double- and single-stranded DNA-binding proteins. by Tanuma Y, Nakabayashi H, Esumi M, Endo H.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232003

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A splice junction mutation causes deletion of a 72-base exon from the mRNA for lysosomal acid lipase in a patient with cholesteryl ester storage disease. by Klima H, Ullrich K, Aslanidis C, Fehringer P, Lackner KJ, Schmitz G.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=288469

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Abnormal Lipoprotein Lipase in Familial Exogenous Hypertriglyceridemia. by Schreibman PH, Arons DL, Saudek CD, Arky RA.; 1973 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302490

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Activation of a Bacterial Lipase by its Chaperone. by Hobson AH, Buckley CM, Aamand JL, Jorgensen ST, Diderichsen B, McConnell DJ.; 1993 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46785

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Activation of hormone-sensitive lipase and phosphorylase kinase by purified cyclic GMP-dependent protein kinase. by Khoo JC, Sperry PJ, Gill GN, Steinberg D.; 1977 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=432052

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Amino acid substitution (Ile194----Thr) in exon 5 of the lipoprotein lipase gene causes lipoprotein lipase deficiency in three unrelated probands. Support for a multicentric origin. by Henderson HE, Ma Y, Hassan MF, Monsalve MV, Marais AD, Winkler F, Gubernator K, Peterson J, Brunzell JD, Hayden MR.; 1991 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296955

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An additional MspI RFLP at the human hepatic lipase (HL) gene locus. by Van Eyk R, Chan L, Top B, Stalenhoef AF, Havekes LM, Frants RR.; 1990 May 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=330900

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An ethylene-induced cDNA encoding a lipase expressed at the onset of senescence. by Hong Y, Wang TW, Hudak KA, Schade F, Froese CD, Thompson JE.; 2000 Jul 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27014

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Anaerobically controlled expression system derived from the arcDABC operon of Pseudomonas aeruginosa: application to lipase production. by Winteler HV, Schneidinger B, Jaeger KE, Haas D.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168137

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Another hormone-sensitive triglyceride lipase in fat cells? by Saltiel AR.; 2000 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33961

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Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo. by Ginsberg HN, Le NA, Goldberg IJ, Gibson JC, Rubinstein A, Wang-Iverson P, Norum R, Brown WV.; 1986 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423815

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Apolipoprotein C-II deficiency syndrome. Clinical features, lipoprotein characterization, lipase activity, and correction of hypertriglyceridemia after apolipoprotein C-II administration in two affected patients. by Baggio G, Manzato E, Gabelli C, Fellin R, Martini S, Enzi GB, Verlato F, Baiocchi MR, Sprecher DL, Kashyap ML, et al.; 1986 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423374

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Application of a Specific and Sensitive Radiometric Assay for Microbial Lipase Activities in Marine Water Samples from the Lagoon of Noumea. by Bourguet N, Torreton JP, Galy O, Arondel V, Goutx M.; 2003 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=309873

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Association of plasma lipoproteins with postheparin lipase activities. by Goldberg IJ, Kandel JJ, Blum CB, Ginsberg HN.; 1986 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423910

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ATP-Dependent and Cyclic AMP-Dependent Activation of Rat Adipose Tissue Lipase by Protein Kinase from Rabbit Skeletal Muscle. by Huttunen JK, Steinberg D, Mayer SE.; 1970 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=283201

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Aut5/Cvt17p, a Putative Lipase Essential for Disintegration of Autophagic Bodies inside the Vacuole. by Epple UD, Suriapranata I, Eskelinen EL, Thumm M.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99673

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Ava-II RFLP at the human hepatic lipase (HL) gene locus. by Li SR, Chan L, Thorn J, Baroni M, Oelbaum R, Galton DJ, Stocks J.; 1989 Jun 26; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318071

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Bcl-1 RFLP at the human hepatic lipase gene locus (CIPC). by Li SR, Chan L, Thorn J, Galton DJ, Stocks J.; 1991 Jan 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333569

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Binding of diamine oxidase activity to rat and guinea pig microvascular endothelial cells. Comparisons with lipoprotein lipase binding. by Robinson-White A, Baylin SB, Olivecrona T, Beaven MA.; 1985 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423716

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Biochemical properties of a novel metalloprotease from Staphylococcus hyicus subsp. hyicus involved in extracellular lipase processing. by Ayora S, Lindgren PE, Gotz F.; 1994 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205491

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bldA-dependent expression of the Streptomyces exfoliatus M11 lipase gene (lipA) is mediated by the product of a contiguous gene, lipR, encoding a putative transcriptional activator. by Servin-Gonzalez L, Castro C, Perez C, Rubio M, Valdez F.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179747

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Bovine milk lipoprotein lipase transfers tocopherol to human fibroblasts during triglyceride hydrolysis in vitro. by Traber MG, Olivecrona T, Kayden HJ.; 1985 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=425518

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Brain monoglyceride lipase participating in endocannabinoid inactivation. by Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, Kathuria S, Piomelli D.; 2002 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125056

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Bst NI (Eco RII) RFLP in the lipoprotein lipase gene (LPL). by Funke H, Reckwerth A, Stapenhorst D, Schulze Beiering M, Jansen M, Assmann G.; 1988 Mar 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=336422

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Bst-1 RFLP at the human lipoprotein lipase (LPL) gene locus. by Li S, Oka K, Galton D, Stocks J.; 1988 Dec 23; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=339154

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Catalytically inactive lipoprotein lipase expression in muscle of transgenic mice increases very low density lipoprotein uptake: Direct evidence that lipoprotein lipase bridging occurs in vivo. by Merkel M, Kako Y, Radner H, Cho IS, Ramasamy R, Brunzell JD, Goldberg IJ, Breslow JL.; 1998 Nov 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24920

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Cell-Bound Lipase and Esterase of Brevibacterium linens. by Sorhaug T, Ordal ZJ.; 1974 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=380093

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Characterization of an Extracellular Lipase Encoded by LIP2 in Yarrowia lipolytica. by Pignede G, Wang H, Fudalej F, Gaillardin C, Seman M, Nicaud JM.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101989

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Characterization of lipase activities in obese Pima indians. Decreases with weight reduction. by Reitman JS, Kosmakos FC, Howard BV, Taskinen MR, Kuusi T, Nikkila EA.; 1982 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370287

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Characterization of lipase-deficient mutants of Acinetobacter calcoaceticus BD413: identification of a periplasmic lipase chaperone essential for the production of extracellular lipase. by Kok RG, van Thor JJ, Nugteren-Roodzant IM, Vosman B, Hellingwerf KJ.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177023

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Characterization of the human lipoprotein lipase (LPL) promoter: evidence of two cisregulatory regions, LP-alpha and LP-beta, of importance for the differentiation-linked induction of the LPL gene during adipogenesis. by Enerback S, Ohlsson BG, Samuelsson L, Bjursell G.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=360389

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Characterization of the Vibrio cholerae El Tor lipase operon lipAB and a protease gene downstream of the hly region. by Ogierman MA, Fallarino A, Riess T, Williams SG, Attridge SR, Manning PA.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179649

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Cloning of chlorophyllase, the key enzyme in chlorophyll degradation: Finding of a lipase motif and the induction by methyl jasmonate. by Tsuchiya T, Ohta H, Okawa K, Iwamatsu A, Shimada H, Masuda T, Takamiya KI.; 1999 Dec 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24824

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Cloning of rat hepatic lipase cDNA: evidence for a lipase gene family. by Komaromy MC, Schotz MC.; 1987 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304467

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Cloning of the Pseudomonas glumae lipase gene and determination of the active site residues. by Frenken LG, Egmond MR, Batenburg AM, Bos JW, Visser C, Verrips CT.; 1992 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183182

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Cloning, expression, and nucleotide sequence of a lipase gene from Pseudomonas fluorescens B52. by Tan Y, Miller KJ.; 1992 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=195611

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Cloning, sequence, and expression of a lipase gene from Pseudomonas cepacia: lipase production in heterologous hosts requires two Pseudomonas genes. by Jorgensen S, Skov KW, Diderichsen B.; 1991 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207046

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Colipase and maximally activated pancreatic lipase in normal subjects and patients with steatorrhea. by Gaskin KJ, Durie PR, Hill RE, Lee LM, Forstner GG.; 1982 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370992

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Complete nucleotide sequence of the lipase gene from Staphylococcus hyicus cloned in Staphylococcus carnosus. by Gotz F, Popp F, Korn E, Schleifer KH.; 1985 Aug 26; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=321920

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Construction of Yeast Strains with High Cell Surface Lipase Activity by Using Novel Display Systems Based on the Flo1p Flocculation Functional Domain. by Matsumoto T, Fukuda H, Ueda M, Tanaka A, Kondo A.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124111

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Development and analytic validation of an enzyme-linked immunosorbent assay for the measurement of canine pancreatic lipase immunoreactivity in serum. by Steiner JM, Teague SR, Williams DA.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=227049

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Development of a Lipase Fermentation Process That Uses a Recombinant Pseudomonas alcaligenes Strain. by Gerritse G, Hommes RW, Quax WJ.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106439

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Direct detection and automated sequencing of individual alleles after electrophoretic strand separation: identification of a common nonsense mutation in exon 9 of the human lipoprotein lipase gene. by Hata A, Robertson M, Emi M, Lalouel JM.; 1990 Sep 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=332217

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Distribution of apolipoprotein(a) in the plasma from patients with lipoprotein lipase deficiency and with type III hyperlipoproteinemia. No evidence for a triglyceride-rich precursor of lipoprotein(a). by Sandholzer C, Feussner G, Brunzell J, Utermann G.; 1992 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=443258

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Disulfide Bond in Pseudomonas aeruginosa Lipase Stabilizes the Structure but Is Not Required for Interaction with Its Foldase. by Liebeton K, Zacharias A, Jaeger KE.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94915

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DNA sequence of lipoprotein lipase cDNA cloned from human monocytic leukemia THP-1 cells. by Takagi A, Ikeda Y, Yamamoto A.; 1990 Nov 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=332549

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Domain exchange: characterization of a chimeric lipase of hepatic lipase and lipoprotein lipase. by Wong H, Davis RC, Nikazy J, Seebart KE, Schotz MC.; 1991 Dec 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53120

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Effect of clindamycin, erythromycin, lincomycin, and tetracycline on growth and extracellular lipase production by propionibacteria in vitro. by Unkles SE, Gemmell CG.; 1982 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=181825

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Effect of feeding and obesity on lipoprotein lipase activity, immunoreactive protein, and messenger RNA levels in human adipose tissue. by Ong JM, Kern PA.; 1989 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303983

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Effect of Heparin on the Inactivation of Serum Lipoprotein Lipase by the Liver in Unanesthetized Dogs. by Whayne TF Jr, Felts JM, Harris PA.; 1969 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=322346

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Effect of heparin-induced lipolysis on the distribution of apolipoprotein e among lipoprotein subclasses. Studies with patients deficient in hepatic triglyceride lipase and lipoprotein lipase. by Rubinstein A, Gibson JC, Paterniti JR Jr, Kakis G, Little A, Ginsberg HN, Brown WV.; 1985 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423564

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Effect of tumor necrosis factor (TNF) on lipid metabolism in the diabetic rat. Evidence that inhibition of adipose tissue lipoprotein lipase activity is not required for TNFinduced hyperlipidemia. by Feingold KR, Soued M, Staprans I, Gavin LA, Donahue ME, Huang BJ, Moser AH, Gulli R, Grunfeld C.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303797

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Effects of insulin and exercise on muscle lipoprotein lipase activity in man and its relation to insulin action. by Kiens B, Lithell H, Mikines KJ, Richter EA.; 1989 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329768

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Endothelial lipase is a major determinant of HDL level. by Ishida T, Choi S, Kundu RK, Hirata KI, Rubin EM, Cooper AD, Quertermous T.; 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151857

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Endothelial lipase is a major genetic determinant for high-density lipoprotein concentration, structure, and metabolism. by Ma K, Cilingiroglu M, Otvos JD, Ballantyne CM, Marian AJ, Chan L.; 2003 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151412

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Expression of the Staphylococcus hyicus Lipase in Lactococcus lactis. by Drouault S, Corthier G, Ehrlich SD, Renault P.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91867

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Extracellular lipase of Pseudomonas sp. strain ATCC 21808: purification, characterization, crystallization, and preliminary X-ray diffraction data. by Kordel M, Hofmann B, Schomburg D, Schmid RD.; 1991 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208163

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Familial chylomicronemia (type I hyperlipoproteinemia) due to a single missense mutation in the lipoprotein lipase gene. by Ameis D, Kobayashi J, Davis RC, Ben-Zeev O, Malloy MJ, Kane JP, Lee G, Wong H, Havel RJ, Schotz MC.; 1991 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=295125

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Fat Digestion in the Newborn CHARACTERIZATION OF LIPASE IN GASTRIC ASPIRATES OF PREMATURE AND TERM INFANTS. by Hamosh M, Scanlon JW, Ganot D, Likel M, Scanlon KB, Hamosh P.; 1981 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370635

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Gene cloning, sequence analysis, purification, and secretion by Escherichia coli of an extracellular lipase from Serratia marcescens. by Li X, Tetling S, Winkler UK, Jaeger KE, Benedik MJ.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=167541

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Gene Organization and Primary Structure of Human Hormone-Sensitive Lipase: Possible Significance of a Sequence Homology with a Lipase of Moraxella TA144, an Antarctic Bacterium. by Langin D, Laurell H, Holst LS, Belfrage P, Holm C.; 1993 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46620

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Genetic and biochemical characterization of a new extracellular lipase from Streptomyces cinnamomeus. by Sommer P, Bormann C, Gotz F.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168661

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Genetic study of common variants at the Apo E, Apo AI, Apo CIII, Apo B, lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes and coronary artery disease (CAD): variation in LIPC gene associates with clinical outcomes in patients with established CAD. by Baroni MG, Berni A, Romeo S, Arca M, Tesorio T, Sorropago G, Di Mario U, Galton DJ.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201027

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Heparin-binding defective lipoprotein lipase is unstable and causes abnormalities in lipid delivery to tissues. by Lutz EP, Merkel M, Kako Y, Melford K, Radner H, Breslow JL, Bensadoun A, Goldberg IJ.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=209279

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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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Heterogeneous mutations in the human lipoprotein lipase gene in patients with familial lipoprotein lipase deficiency. by Gotoda T, Yamada N, Kawamura M, Kozaki K, Mori N, Ishibashi S, Shimano H, Takaku F, Yazaki Y, Furuichi Y, et al.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=295753

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High density lipoprotein2. Relationship of the plasma levels of this lipoprotein species to its composition, to the magnitude of postprandial lipemia, and to the activities of lipoprotein lipase and hepatic lipase. by Patsch JR, Prasad S, Gotto AM Jr, Patsch W.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=442243

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High-affinity salicylic acid-binding protein 2 is required for plant innate immunity and has salicylic acid-stimulated lipase activity. by Kumar D, Klessig DF.; 2003 Dec 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=307699

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High-Level Formation of Active Pseudomonas cepacia Lipase after Heterologous Expression of the Encoding Gene and Its Modified Chaperone in Escherichia coli and Rapid In Vitro Refolding. by Quyen DT, Schmidt-Dannert C, Schmid RD.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91096

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Homologous Expression of the Lipase and ABC Transporter Gene Cluster, tliDEFA, Enhances Lipase Secretion in Pseudomonas spp. by Ahn JH, Pan JG, Rhee JS.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93336

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Homology of lipoprotein lipase to pancreatic lipase. by Ben-Avram CM, Ben-Zeev O, Lee TD, Haaga K, Shively JE, Goers J, Pedersen ME, Reeve JR Jr, Schotz MC.; 1986 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=323696

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Hormonal regulation of hormone-sensitive lipase in intact adipocytes: identification of phosphorylated sites and effects on the phosphorylation by lipolytic hormones and insulin. by Stralfors P, Bjorgell P, Belfrage P.; 1984 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=345498

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Hormone-sensitive lipase in differentiated 3T3-L1 cells and its activation by cyclic AMP-dependent protein kinase. by Kawamura M, Jensen DF, Wancewicz EV, Joy LL, Khoo JC, Steinberg D.; 1981 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=319876

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Identification of the tliDEF ABC Transporter Specific for Lipase in Pseudomonas fluorescens SIK W1. by Ahn JH, Pan JG, Rhee JS.; 1999 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93584

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Identification, Purification, and Characterization of a Thermally Stable Lipase from Rice Bran. A New Member of the (Phospho) Lipase Family. by Bhardwaj K, Raju A, Rajasekharan R.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133576

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Increase of adipose tissue lipoprotein lipase activity with weight loss. by Schwartz RS, Brunzell JD.; 1981 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370709

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Induced mutant mouse lines that express lipoprotein lipase in cardiac muscle, but not in skeletal muscle and adipose tissue, have normal plasma triglyceride and highdensity lipoprotein-cholesterol levels. by Levak-Frank S, Hofmann W, Weinstock PH, Radner H, Sattler W, Breslow JL, Zechner R.; 1999 Mar 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15913

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Inhibition of endothelial lipase causes increased HDL cholesterol levels in vivo. by Jin W, Millar JS, Broedl U, Glick JM, Rader DJ.; 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151853

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Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein. by Shen WJ, Sridhar K, Bernlohr DA, Kraemer FB.; 1999 May 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21893

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Intercellular transport of lysosomal acid lipase mediates lipoprotein cholesteryl ester metabolism in a human vascular endothelial cell-fibroblast coculture system. by Sando GN, Ma GP, Lindsley KA, Wei YP.; 1990 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=361630

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Involvement of cell surface heparin sulfate in the binding of lipoprotein lipase to cultured bovine endothelial cells. by Shimada K, Gill PJ, Silbert JE, Douglas WH, Fanburg BL.; 1981 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370886

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Lingual Lipase and Its Role in the Digestion of Dietary Lipid. by Hamosh M, Scow RO.; 1973 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302230

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Lingual lipase in cystic fibrosis. Quantitation of enzyme activity in the upper small intestine of patients with exocrine pancreatic insufficiency. by Abrams CK, Hamosh M, Hubbard VS, Dutta SK, Hamosh P.; 1984 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=425027

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Lipase and Its Modulator from Pseudomonas sp. Strain KFCC 10818: Proline-toGlutamine Substitution at Position 112 Induces Formation of Enzymatically Active Lipase in the Absence of the Modulator. by Kim EK, Jang WH, Ko JH, Kang JS, Noh MJ, Yoo OJ.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99672

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Lipases of the euphorbiaceae family: purification of a lipase from Euphorbia characias latex and structure-function relationships with the B chain of ricin. by Moulin A, Teissere M, Bernard C, Pieroni G.; 1994 Nov 22; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=45224

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Lipopolysaccharide regulation of lipoprotein lipase expression in murine macrophages. by Hill MR, Kelly K, Wu X, Wanker F, Bass H, Morgan C, Wang C, Gimble JM.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173082

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Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy. by Yagyu H, Chen G, Yokoyama M, Hirata K, Augustus A, Kako Y, Seo T, Hu Y, Lutz EP, Merkel M, Bensadoun A, Homma S, Goldberg IJ.; 2003 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151861

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Lipoprotein lipase cofactor activity of a carboxyl-terminal peptide of apolipoprotein C-II. by Musliner TA, Church EC, Herbert PN, Kingston MJ, Shulman RS.; 1977 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=431719

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Lipoprotein lipase controls fatty acid entry into adipose tissue, but fat mass is preserved by endogenous synthesis in mice deficient in adipose tissue lipoprotein lipase. by Weinstock PH, Levak-Frank S, Hudgins LC, Radner H, Friedman JM, Zechner R, Breslow JL.; 1997 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23350

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Lipoprotein lipase enhances binding of lipoproteins to heparan sulfate on cell surfaces and extracellular matrix. by Eisenberg S, Sehayek E, Olivecrona T, Vlodavsky I.; 1992 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=443265

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Lipoprotein lipase enhances the binding of chylomicrons to low density lipoprotein receptor-related protein. by Beisiegel U, Weber W, Bengtsson-Olivecrona G.; 1991 Oct 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52504

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Lipoprotein lipase increases low density lipoprotein retention by subendothelial cell matrix. by Saxena U, Klein MG, Vanni TM, Goldberg IJ.; 1992 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=442862

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Lipoprotein lipase is produced, regulated, and functional in rat brain. by Eckel RH, Robbins RJ.; 1984 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=392196

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Lipoprotein lipase is synthesized by macrophage-derived foam cells in human coronary atherosclerotic plaques. by O'Brien KD, Gordon D, Deeb S, Ferguson M, Chait A.; 1992 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=443027

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Lipoprotein lipase modulates net secretory output of apolipoprotein B in vitro. A possible pathophysiologic explanation for familial combined hyperlipidemia. by Williams KJ, Petrie KA, Brocia RW, Swenson TL.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=295599

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Lipoprotein lipase secretion by human monocyte-derived macrophages. by Chait A, Iverius PH, Brunzell JD.; 1982 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370999

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Lipoprotein lipase secretion by human monocytes and rabbit alveolar macrophages in culture. by Mahoney EM, Khoo JC, Steinberg D.; 1982 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=346031

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Lipoprotein lipase suppression in 3T3-L1 cells by an endotoxin-induced mediator from exudate cells. by Kawakami M, Pekala PH, Lane MD, Cerami A.; 1982 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=345863

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Lipoprotein Metabolism during Acute Inhibition of Hepatic Triglyceride Lipase in the Cynomolgus Monkey. by Goldberg IJ, Le NA, Paterniti JR Jr, Ginsberg HN, Lindgren FT, Brown WV.; 1982 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370335

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Localization of a chromosomal mutation affecting expression of extracellular lipase in Staphylococcus aureus. by Smeltzer MS, Gill SR, Iandolo JJ.; 1992 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206109

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Low-Temperature Lipase from Psychrotrophic Pseudomonas sp. Strain KB700A. by Rashid N, Shimada Y, Ezaki S, Atomi H, Imanaka T.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93130

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Lysogenic conversion of staphylococcal lipase is caused by insertion of the bacteriophage L54a genome into the lipase structural gene. by Lee CY, Iandolo JJ.; 1986 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214616

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Macrophages and smooth muscle cells express lipoprotein lipase in human and rabbit atherosclerotic lesions. by Yla-Herttuala S, Lipton BA, Rosenfeld ME, Goldberg IJ, Steinberg D, Witztum JL.; 1991 Nov 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52884

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Mechanism of bacteriophage conversion of lipase activity in Staphylococcus aureus. by Lee CY, Iandolo JJ.; 1985 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214242

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Mechanism of hormone-stimulated lipolysis in adipocytes: translocation of hormonesensitive lipase to the lipid storage droplet. by Egan JJ, Greenberg AS, Chang MK, Wek SA, Moos MC Jr, Londos C.; 1992 Sep 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49955

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Modulation of lipoprotein lipase activity by apolipoproteins. Effect of apolipoprotein C-III. by Wang CS, McConathy WJ, Kloer HU, Alaupovic P.; 1985 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423500

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Molecular cloning and nucleotide sequence of rat lingual lipase cDNA. by Docherty AJ, Bodmer MW, Angal S, Verger R, Riviere C, Lowe PA, Lyons A, Emtage JS, Harris TJ.; 1985 Mar 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341123

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Molecular studies on primary lipoprotein lipase (LPL) deficiency. One base deletion (G916) in exon 5 of LPL gene causes no detectable LPL protein due to the absence of LPL mRNA transcript. by Takagi A, Ikeda Y, Tsutsumi Z, Shoji T, Yamamoto A.; 1992 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=442891

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Muscle-specific overexpression of lipoprotein lipase causes a severe myopathy characterized by proliferation of mitochondria and peroxisomes in transgenic mice. by Levak-Frank S, Radner H, Walsh A, Stollberger R, Knipping G, Hoefler G, Sattler W, Weinstock PH, Breslow JL, Zechner R.; 1995 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185285

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Neutrophil chemotaxis by Propionibacterium acnes lipase and its inhibition. by Lee WL, Shalita AR, Suntharalingam K, Fikrig SM.; 1982 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=350997

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Nucleotide sequence of human cDNA coding for a lipoprotein lipase (LPL) cloned from placental cDNA library. by Gotoda T, Senda M, Gamou T, Furuichi Y, Oka K.; 1989 Mar 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=317600

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Nucleotide sequence of PvuII polymorphic site at the human lipoprotein lipase gene locus. by Oka K, Tkalcevic GT, Stocks J, Galton DJ, Brown WV.; 1989 Aug 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318390

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Nucleotide sequence of rat adipose hormone sensitive lipase cDNA. by Holm C, Kirchgessner TG, Svenson KL, Lusis AJ, Belfrage P, Schotz MC.; 1988 Oct 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=338807

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Optimal Step Length EM Algorithm (OSLEM) for the estimation of haplotype frequency and its application in lipoprotein lipase genotyping. by Zhang P, Sheng H, Morabia A, Gilliam TC.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149347

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Oral Treatment with Lactococcus lactis Expressing Staphylococcus hyicus Lipase Enhances Lipid Digestion in Pigs with Induced Pancreatic Insufficiency. by Drouault S, Juste C, Marteau P, Renault P, Corthier G.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123933

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Organization of the human lipoprotein lipase gene and evolution of the lipase gene family. by Kirchgessner TG, Chuat JC, Heinzmann C, Etienne J, Guilhot S, Svenson K, Ameis D, Pilon C, d'Auriol L, Andalibi A, et al.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298558

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Overexpression of hepatic lipase in transgenic rabbits leads to a marked reduction of plasma high density lipoproteins and intermediate density lipoproteins. by Fan J, Wang J, Bensadoun A, Lauer SJ, Dang Q, Mahley RW, Taylor JM.; 1994 Aug 30; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44679

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Pharyngeal lipase and digestion of dietary triglyceride in man. by Hamosh M, Klaeveman HL, Wolf RO, Scow RO.; 1975 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301833

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Phase variation in Xenorhabdus luminescens: cloning and sequencing of the lipase gene and analysis of its expression in primary and secondary phases of the bacterium. by Wang H, Dowds BC.; 1993 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=203960

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Phase-Variable Expression of an Operon Encoding Extracellular Alkaline Protease, a Serine Protease Homolog, and Lipase in Pseudomonas brassicacearum. by Chabeaud P, de Groot A, Bitter W, Tommassen J, Heulin T, Achouak W.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95110

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Phenotypic expression of heterozygous lipoprotein lipase deficiency in the extended pedigree of a proband homozygous for a missense mutation. by Wilson DE, Emi M, Iverius PH, Hata A, Wu LL, Hillas E, Williams RR, Lalouel JM.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296788

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Phospholipase C-gamma 1 can induce DNA synthesis by a mechanism independent of its lipase activity. by Smith MR, Liu YL, Matthews NT, Rhee SG, Sung WK, Kung HF.; 1994 Jul 5; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44241

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Physiological factors affecting production of extracellular lipase (LipA) in Acinetobacter calcoaceticus BD413: fatty acid repression of lipA expression and degradation of LipA. by Kok RG, Nudel CB, Gonzalez RH, Nugteren-Roodzant IM, Hellingwerf KJ.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178462

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Production of lipase by clinical isolates of Pseudomonas cepacia. by Lonon MK, Woods DE, Straus DC.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266500

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Production, purification, and properties of a lipase from a bacterium (Pseudomonas aeruginosa YS-7) capable of growing in water-restricted environments. by Shabtai Y, Daya-Mishne N.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=195188

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Purification and partial characterization of an alkaline lipase from Pseudomonas pseudoalcaligenes F-111. by Lin SF, Chiou CM, Yeh CM, Tsai YC.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=167873

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Purification of extracellular lipase from Pseudomonas aeruginosa. by Stuer W, Jaeger KE, Winkler UK.; 1986 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213604

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Purification, gene cloning, amino acid sequence analysis, and expression of an extracellular lipase from an Aeromonas hydrophila human isolate. by Anguita J, Rodriguez Aparicio LB, Naharro G.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182299

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Pvu-II RFLP at the human lipoprotein lipase (LPL) gene locus. by Li SR, Oka K, Galton D, Stocks J.; 1988 Mar 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=338244

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Recombinant human cachectin/tumor necrosis factor but not interleukin-1 alpha downregulates lipoprotein lipase gene expression at the transcriptional level in mouse 3T3-L1 adipocytes. by Zechner R, Newman TC, Sherry B, Cerami A, Breslow JL.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=363437

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Regulation of lipoprotein lipase in primary cultures of isolated human adipocytes. by Kern PA, Marshall S, Eckel RH.; 1985 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423427

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Regulation of lipoprotein lipase in the diabetic rat. by Tavangar K, Murata Y, Pedersen ME, Goers JF, Hoffman AR, Kraemer FB.; 1992 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=443223

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Regulation of lipoprotein lipase translation by epinephrine in 3T3-L1 cells. Importance of the 3' untranslated region. by Yukht A, Davis RC, Ong JM, Ranganathan G, Kern PA.; 1995 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185896

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Regulation of Mammary and Adipose Tissue Lipoprotein Lipase and Blood Triacylglycerol in Rats during Late Pregnancy EFFECT OF PROSTAGLANDINS. by Spooner PM, Garrison MM, Scow RO.; 1977 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372415

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Responses of Adipose and Muscle Lipoprotein Lipase to Chronic Infection and Subsequent Acute Lipopolysaccharide Challenge. by Picard F, Arsenijevic D, Richard D, Deshaies Y.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120025

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RFLP for the human lipoprotein lipase (LPL) gene: HindIII. by Heinzmann C, Ladias J, Antonarakis S, Kirchgessner T, Schotz M, Lusis AJ.; 1987 Aug 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=306163

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Role of lipoprotein lipase in the regulation of high density lipoprotein apolipoprotein metabolism. Studies in normal and lipoprotein lipase-inhibited monkeys. by Goldberg IJ, Blaner WS, Vanni TM, Moukides M, Ramakrishnan R.; 1990 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296748

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Role of Phospholipase C-L2, a Novel Phospholipase C-Like Protein That Lacks Lipase Activity, in B-Cell Receptor Signaling. by Takenaka K, Fukami K, Otsuki M, Nakamura Y, Kataoka Y, Wada M, Tsuji K, Nishikawa SI, Yoshida N, Takenawa T.; 2003 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=230318

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Role of Pseudomonas aeruginosa lipase in inflammatory mediator release from human inflammatory effector cells (platelets, granulocytes, and monocytes. by Konig B, Jaeger KE, Sage AE, Vasil ML, Konig W.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174215

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Selective Measurement of Two Lipase Activities in Postheparin Plasma from Normal Subjects and Patients with Hyperlipoproteinemia. by Krauss RM, Levy RI, Fredrickson DS.; 1974 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301659

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Sequence Analysis of Amplified DNA Fragments Containing the Region Encoding the Putative Lipase Substrate-Binding Domain and Genotyping of Aeromonas hydrophila. by Watanabe N, Morita K, Furukawa T, Manzoku T, Endo E, Kanamori M.; 2004 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=321285

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Sequence of a lipase gene from the antarctic psychrotroph Moraxella TA144. by Feller G, Thiry M, Gerday C.; 1990 Nov 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=332543

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Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes. by Weinstock PH, Bisgaier CL, AaltoSetala K, Radner H, Ramakrishnan R, Levak-Frank S, Essenburg AD, Zechner R, Breslow JL.; 1995 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185959

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Stimulation of Lipase Production During Bacterial Growth on Alkanes. by Breuil C, Shindler DB, Sijher JS, Kushner DJ.; 1978 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=222064

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Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity. by Osuga JI, Ishibashi S, Oka T, Yagyu H, Tozawa R, Fujimoto A, Shionoiri F, Yahagi N, Kraemer FB, Tsutsumi O, Yamada N.; 2000 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15409

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Tetracycline Inhibition of a Lipase from Corynebacterium acnes. by Weaber K, Freedman R, Eudy WW.; 1971 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=377246

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The effect of estrogen on the lipoprotein lipase activity of rat adipose tissue. by Hamosh M, Hamosh P.; 1975 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301861

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The lipA gene of Serratia marcescens which encodes an extracellular lipase having no N-terminal signal peptide. by Akatsuka H, Kawai E, Omori K, Komatsubara S, Shibatani T, Tosa T.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205299

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The Lipase Engineering Database: a navigation and analysis tool for protein families. by Fischer M, Pleiss J.; 2003 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165462

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The Mechanism of Activation of Hormone-Sensitive Lipase in Human Adipose Tissue. by Khoo JC, Aquino AA, Steinberg D.; 1974 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333098

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THE REMOVAL OF LIPOPROTEIN LIPASE FROM THE BLOOD BY THE NORMAL AND DISEASED LIVER. by Connor WE, Eckstein JW.; 1959 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=444142

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The three genes lipB, lipC, and lipD involved in the extracellular secretion of the Serratia marcescens lipase which lacks an N-terminal signal peptide. by Akatsuka H, Kawai E, Omori K, Shibatani T.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177487

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Tissue Lipoprotein Lipase in Normal Individuals and in Individuals with Exogenous Hypertriglyceridemia and the Relationship of This Enzyme to Assimilation of Fat. by Harlan WR Jr, Winesett PS, Wasserman AJ.; 1967 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297042

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Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. by Kim JK, Fillmore JJ, Chen Y, Yu C, Moore IK, Pypaert M, Lutz EP, Kako Y, Velez-Carrasco W, Goldberg IJ, Breslow JL, Shulman GI.; 2001 Jun 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34701

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Transport of lipoprotein lipase across endothelial cells. by Saxena U, Klein MG, Goldberg IJ.; 1991 Mar 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51209

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Two polymorphisms for the human hepatic lipase (HL) gene. by Heinzmann C, Ladias J, Antonarakis S, Diep A, Schotz M, Lusis AJ.; 1988 May 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=336678

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Two polymorphisms in the human lipoprotein lipase (LPL) gene. by Fisher KL, FitzGerald GA, Lawn RM.; 1987 Sep 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=306290

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Two RFLPs at the lipoprotein lipase (LPL) gene. by Hegele RA, Nakamura Y, Emi M, Lalouel JM, White R.; 1989 Dec 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=335281

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Use of monoclonal antibodies to demonstrate different sites with different functional characteristics in a bacterial lipase from Pseudomonas aeruginosa YS-7. by DayaMishne N, Shabtai Y.; 1992 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=195301

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Use of the pre-pro part of Staphylococcus hyicus lipase as a carrier for secretion of Escherichia coli outer membrane protein A (OmpA) prevents proteolytic degradation of OmpA by cell-associated protease(s) in two different gram-positive bacteria. by Meens J, Herbort M, Klein M, Freudl R.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168578

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Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels. by Cohen JC, Wang Z, Grundy SM, Stoesz MR, Guerra R.; 1994 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=330067

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VNTR polymorphism in the hepatic lipase gene (LIPC). by Bhattacharya S, Ameis D, Cullen P, Narcisi TM, Bayliss J, Greten H, Schotz MC, Scott J.; 1991 Sep 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=328828

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Weight reduction increases adipose tissue lipoprotein lipase responsiveness in obese women. by Eckel RH, Yost TJ.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=442337

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Xmn-1 and Bg1-II RFLPs at the human hepatic lipase (HL) gene locus. by Li SR, Chan L, Thorn J, Galton DJ, Stocks J.; 1989 Aug 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318400

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with lipase, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “lipase” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for lipase (hyperlinks lead to article summaries):

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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A case of subcutaneous nodular fat necrosis with lipase-secreting acinar cell carcinoma. Author(s): Ohno Y, Le Pavoux A, Saeki H, Asahina A, Tamaki K. Source: International Journal of Dermatology. 2003 May; 42(5): 384-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12755979

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A common truncated variant of lipoprotein lipase in the Japanese population is characterized by pattern B phenotype. Author(s): Li J, Kondo A, Kanno T, Maekawa M. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2003 October; 41(10): 1304-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14580156

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A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) contributes to the expression of familial combined hyperlipidemia. Author(s): Reymer PW, Groenemeyer BE, Gagne E, Miao L, Appelman EE, Seidel JC, Kromhout D, Bijvoet SM, van de Oever K, Bruin T, et al. Source: Human Molecular Genetics. 1995 September; 4(9): 1543-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8541837

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A G----C change at the donor splice site of intron 1 causes lipoprotein lipase deficiency in a southern-Italian family. Author(s): Chimienti G, Capurso A, Resta F, Pepe G. Source: Biochemical and Biophysical Research Communications. 1992 September 16; 187(2): 620-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1530621

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A missense mutation Pro157 Arg in lipoprotein lipase (LPLNijmegen) resulting in loss of catalytic activity. Author(s): Bruin T, Kastelein JJ, Van Diermen DE, Ma Y, Henderson HE, Stuyt PM, Stalenhoef AF, Sturk A, Brunzell JD, Hayden MR. Source: European Journal of Biochemistry / Febs. 1992 September 1; 208(2): 267-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1521525

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A novel hormone-sensitive lipase isoform expressed in pancreatic beta-cells. Author(s): Lindvall H, Nevsten P, Strom K, Wallenberg R, Sundler F, Langin D, Winzell MS, Holm C. Source: The Journal of Biological Chemistry. 2004 January 30; 279(5): 3828-36. Epub 2003 October 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14576146

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A novel polymorphism A(+884)-->G in the hepatic lipase gene and its association with coronary artery disease. Author(s): Su ZG, Zhang SZ, Zhang L, Tong Y, Xiao CY, Hou YP, Liao LC. Source: Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao Acta Biochimica Et Biophysica Sinica. 2003 July; 35(7): 606-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883629

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A role for monoglyceride lipase in 2-arachidonoylglycerol inactivation. Author(s): Dinh TP, Freund TF, Piomelli D. Source: Chemistry and Physics of Lipids. 2002 December 31; 121(1-2): 149-58. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505697

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Adipose cell size and distribution in familial lipoprotein lipase deficiency. Author(s): Peeva E, Brun LD, Ven Murthy MR, Despres JP, Normand T, Gagne C, Lupien PJ, Julien P. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 1992 October; 16(10): 737-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1330953

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Amylase, lipase, pancreatic isoamylase, and phospholipase A in diagnosis of acute pancreatitis. Author(s): Clave P, Guillaumes S, Blanco I, Nabau N, Merce J, Farre A, Marruecos L, Lluis F. Source: Clinical Chemistry. 1995 August; 41(8 Pt 1): 1129-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7543034

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Analysis of ligand binding to the alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Evidence that lipoprotein lipase and the carboxyl-terminal domain of the receptor-associated protein bind to the same site. Author(s): Nielsen MS, Nykjaer A, Warshawsky I, Schwartz AL, Gliemann J. Source: The Journal of Biological Chemistry. 1995 October 6; 270(40): 23713-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7559542

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Apolipoprotein B and E basic amino acid clusters influence low-density lipoprotein association with lipoprotein lipase anchored to the subendothelial matrix. Author(s): Saxena U, Auerbach BJ, Ferguson E, Wolle J, Marcel YL, Weisgraber KH, Hegele RA, Bisgaier CL. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1995 August; 15(8): 1240-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7627718

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Apolipoprotein B production reduces lipotoxic cardiomyopathy: studies in heartspecific lipoprotein lipase transgenic mouse. Author(s): Yokoyama M, Yagyu H, Hu Y, Seo T, Hirata K, Homma S, Goldberg IJ. Source: The Journal of Biological Chemistry. 2004 February 6; 279(6): 4204-11. Epub 2003 November 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14634011

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Association between lipoprotein lipase (LPL) gene and blood lipids: a common variant for a common trait? Author(s): Morabia A, Cayanis E, Costanza MC, Ross BM, Bernstein MS, Flaherty MS, Alvin GB, Das K, Morris MA, Penchaszadeh GK, Zhang P, Gilliam TC. Source: Genetic Epidemiology. 2003 May; 24(4): 309-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687649

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Association between single-nucleotide polymorphisms in the endothelial lipase (LIPG) gene and high-density lipoprotein cholesterol levels. Author(s): Mank-Seymour AR, Durham KL, Thompson JF, Seymour AB, Milos PM. Source: Biochimica Et Biophysica Acta. 2004 February 27; 1636(1): 40-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14984737

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Association of bile-salt-dependent lipase with membranes of human pancreatic microsomes. Author(s): Bruneau N, de la Porte PL, Sbarra V, Lombardo D. Source: European Journal of Biochemistry / Febs. 1995 October 1; 233(1): 209-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7588748

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Association of lipoprotein lipase Ser447Ter polymorphism with brain infarction: a population-based neuropathological study. Author(s): Myllykangas L, Polvikoski T, Sulkava R, Notkola IL, Rastas S, Verkkoniemi A, Tienari PJ, Niinisto L, Hardy J, Perez-Tur J, Kontula K, Haltia M. Source: Annals of Medicine. 2001 October; 33(7): 486-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11680797

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Association of the hormone sensitive lipase -60C > G variant with fasting insulin levels in healthy young men. Author(s): Talmud PJ, Palmen J, Nicaud V, Tiret L; European Atherosclerosis Research II Study. Source: Nutr Metab Cardiovasc Dis. 2002 August; 12(4): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12514936

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Atorvastatin dose-dependently decreases hepatic lipase activity in type 2 diabetes: effect of sex and the LIPC promoter variant. Author(s): Berk-Planken II, Hoogerbrugge N, Stolk RP, Bootsma AH, Jansen H; DALI Study Group. Source: Diabetes Care. 2003 February; 26(2): 427-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12547874

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Baboon lipoprotein lipase: cDNA sequence and variable tissue-specific expression of two transcripts. Author(s): Cole SA, Hixson JE. Source: Gene. 1995 August 19; 161(2): 265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7665091

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Bile salt-activated lipase. Author(s): Wang CS, Dashti A, Downs D. Source: Methods in Molecular Biology (Clifton, N.J.). 1999; 109: 71-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9918013

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Bile salt-dependent lipase transcripts in human fetal tissues. Author(s): Roudani S, Miralles F, Margotat A, Escribano MJ, Lombardo D. Source: Biochimica Et Biophysica Acta. 1995 October 17; 1264(1): 141-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7578248

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Bile salt-dependent lipase: its pathophysiological implications. Author(s): Lombardo D. Source: Biochimica Et Biophysica Acta. 2001 August 29; 1533(1): 1-28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11514232

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Bile salt-stimulated carboxyl ester lipase influences lipoprotein assembly and secretion in intestine: a process mediated via ceramide hydrolysis. Author(s): Kirby RJ, Zheng S, Tso P, Howles PN, Hui DY. Source: The Journal of Biological Chemistry. 2002 February 8; 277(6): 4104-9. Epub 2001 December 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11733511

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Bile salt-stimulated lipase (BSSL) distribution in rat, mouse and transgenic mouse expressing human BSSL. Author(s): Poorkhalkali N, Lidmer AS, Lundberg LG, Dalrymple MA, Gibson Y, Taylor L, Temperley S, Stromqvist M, Helander HF. Source: Histochemistry and Cell Biology. 1998 October; 110(4): 367-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9792415

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Bile salt-stimulated lipase and digestion of non-breast milk fat. Author(s): McClean P, Harding M, Coward WA, Prentice A, Austin S, Weaver LT. Source: Journal of Pediatric Gastroenterology and Nutrition. 1998 January; 26(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9443118

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Bile salt-stimulated lipase in the milk of Fulani and Kanuri women in Nigeria and native Nepalese women. Author(s): Torres JE, VanderJagt D, Okolo SN, Magnussen M, Bhatta SK, Glew RH. Source: Journal of the National Medical Association. 2001 June; 93(6): 201-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11446391

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Binding and intracellular trafficking of lipoprotein lipase and triacylglycerol-rich lipoproteins by liver cells. Author(s): Casaroli-Marano RP, Garcia R, Vilella E, Olivecrona G, Reina M, Vilaro S. Source: Journal of Lipid Research. 1998 April; 39(4): 789-806. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9555944

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Binding of low density lipoproteins to lipoprotein lipase is dependent on lipids but not on apolipoprotein B. Author(s): Boren J, Lookene A, Makoveichuk E, Xiang S, Gustafsson M, Liu H, Talmud P, Olivecrona G. Source: The Journal of Biological Chemistry. 2001 July 20; 276(29): 26916-22. Epub 2001 April 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11331277

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Binding to heparan sulfate is a major event during catabolism of lipoprotein lipase by HepG2 and other cell cultures. Author(s): Sehayek E, Olivecrona T, Bengtsson-Olivecrona G, Vlodavsky I, Levkovitz H, Avner R, Eisenberg S. Source: Atherosclerosis. 1995 April 7; 114(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7605368

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Biochemical and physical properties of remnant-HDL2 and of pre beta 1-HDL produced by hepatic lipase. Author(s): Guendouzi K, Jaspard B, Barbaras R, Motta C, Vieu C, Marcel Y, Chap H, Perret B, Collet X. Source: Biochemistry. 1999 March 2; 38(9): 2762-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10052947

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Bis-2-oxo amide triacylglycerol analogues: a novel class of potent human gastric lipase inhibitors. Author(s): Kotsovolou S, Chiou A, Verger R, Kokotos G. Source: The Journal of Organic Chemistry. 2001 February 9; 66(3): 962-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11430119

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Black-white differences in postprandial triglyceride response and postheparin lipoprotein lipase and hepatic triglyceride lipase among young men. Author(s): Friday KE, Srinivasan SR, Elkasabany A, Dong C, Wattigney WA, Dalferes E Jr, Berenson GS. Source: Metabolism: Clinical and Experimental. 1999 June; 48(6): 749-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10381150

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Blockade of pancreatic lipase. Author(s): Blackburn GL. Source: The American Journal of Clinical Nutrition. 2000 March; 71(3): 845-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10702184

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Blockade of the glucocorticoid receptor with RU 486: effects in vitro and in vivo on human adipose tissue lipoprotein lipase activity. Author(s): Ottosson M, Marin P, Karason K, Elander A, Bjorntorp P. Source: Obesity Research. 1995 May; 3(3): 233-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7627771

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Blood extracellular superoxide dismutase levels in hemodialysis patients pre- and post-hemodialysis and its association with lipoprotein lipase mass and free fatty acid. Author(s): Shimomura H, Maehata E, Takamiya T, Adachi T, Komoda T. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 February; 328(1-2): 113-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12559606

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Body mass index and hepatic lipase gene (LIPC) polymorphism jointly influence postheparin plasma hepatic lipase activity. Author(s): Nie L, Wang J, Clark LT, Tang A, Vega GL, Grundy SM, Cohen JC. Source: Journal of Lipid Research. 1998 May; 39(5): 1127-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9610782

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Brain monoglyceride lipase participating in endocannabinoid inactivation. Author(s): Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, Kathuria S, Piomelli D. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 August 6; 99(16): 10819-24. Epub 2002 July 22. Erratum In: Proc Natl Acad Sci U S a 2002 October 15; 99(21): 13961. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12136125

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Calreticulin promotes folding/dimerization of human lipoprotein lipase expressed in insect cells (sf21). Author(s): Zhang L, Wu G, Tate CG, Lookene A, Olivecrona G. Source: The Journal of Biological Chemistry. 2003 August 1; 278(31): 29344-51. Epub 2003 May 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740382

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Carboxyl ester lipase cofractionates with scavenger receptor BI in hepatocyte lipid rafts and enhances selective uptake and hydrolysis of cholesteryl esters from HDL3. Author(s): Camarota LM, Chapman JM, Hui DY, Howles PN. Source: The Journal of Biological Chemistry. 2004 June 25; 279(26): 27599-606. Epub 2004 April 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15105424

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Carotid intima-media thickness is associated with allelic variants of stromelysin-1, interleukin-6, and hepatic lipase genes: the Northern Manhattan Prospective Cohort Study. Author(s): Rundek T, Elkind MS, Pittman J, Boden-Albala B, Martin S, Humphries SE, Juo SH, Sacco RL. Source: Stroke; a Journal of Cerebral Circulation. 2002 May; 33(5): 1420-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11988625

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Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 37-2002. A 69-year-old man with painful cutaneous nodules, elevated lipase levels, and abnormal results on abdominal scanning. Author(s): Ashley SW, Lauwers GY. Source: The New England Journal of Medicine. 2002 November 28; 347(22): 1783-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12456855

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Characterization of the C-terminal region of molecular forms of human milk bile saltstimulated lipase. Author(s): McKillop AM, O'Hare MM, Craig JS, Halliday HL. Source: Acta Paediatrica (Oslo, Norway : 1992). 2004 January; 93(1): 10-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14989432

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Characterization of the human lipoprotein lipase (LPL) promoter: evidence of two cisregulatory regions, LP-alpha and LP-beta, of importance for the differentiation-linked induction of the LPL gene during adipogenesis. Author(s): Enerback S, Ohlsson BG, Samuelsson L, Bjursell G. Source: Molecular and Cellular Biology. 1992 October; 12(10): 4622-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1406652

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Characterization of the lipolytic activity of endothelial lipase. Author(s): McCoy MG, Sun GS, Marchadier D, Maugeais C, Glick JM, Rader DJ. Source: Journal of Lipid Research. 2002 June; 43(6): 921-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12032167

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Cholecystokinin-stimulated peak lipase concentration in duodenal drainage fluid: a new pancreatic function test. Author(s): Conwell DL, Zuccaro G, Morrow JB, Van Lente F, Obuchowski N, Vargo JJ, Dumot JA, Trolli P, Shay SS. Source: The American Journal of Gastroenterology. 2002 June; 97(6): 1392-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12094856

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Cholesterol ester transfer protein, apolipoprotein E and lipoprotein lipase genotypes in patients with coronary artery disease in the Turkish population. Author(s): Isbir T, Yilmaz H, Agachan B, Karaali ZE. Source: Clinical Genetics. 2003 September; 64(3): 228-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12919138

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Chylomicronemia caused by lipoprotein lipase gene mutation related to a hyperresponse of insulin secretion to glucose. Author(s): Tanaka S, Tanabe Y, Tamura H, Ishii S, Shuto Y, Kamegai J, Sugihara H, Kobayashi M, Wakabayashi I, Murano T, Shirai K, Oikawa S. Source: Intern Med. 2002 April; 41(4): 300-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11993791

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Circulating bile salt-dependent lipase originates from the pancreas via intestinal transcytosis. Author(s): Bruneau N, Bendayan M, Gingras D, Ghitescu L, Levy E, Lombardo D. Source: Gastroenterology. 2003 February; 124(2): 470-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12557152

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Cloning of rat lysosomal acid lipase cDNA and identification of the mutation in the rat model of Wolman's disease. Author(s): Nakagawa H, Matsubara S, Kuriyama M, Yoshidome H, Fujiyama J, Yoshida H, Osame M. Source: Journal of Lipid Research. 1995 October; 36(10): 2212-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8576647

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Common variants in the lipoprotein lipase gene in Brazil: association with lipids and angiographically assessed coronary atherosclerosis. Author(s): Rios DL, Vargas AF, Ewald GM, Torres MR, Zago AJ, Callegari-Jacques SM, Hutz MH. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2003 October; 41(10): 1351-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14580165

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Common variants in the lipoprotein lipase gene, but not those in the insulin receptor substrate-1, the beta3-adrenergic receptor, and the intestinal fatty acid binding protein-2 genes, influence the lipid phenotypic expression in familial combined hyperlipidemia. Author(s): Campagna F, Montali A, Baroni MG, Maria AT, Ricci G, Antonini R, Verna R, Arca M. Source: Metabolism: Clinical and Experimental. 2002 October; 51(10): 1298-305. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370850

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Commutability of calibration and control materials for serum lipase. Author(s): Cattozzo G, Franzini C, Melzi d'Eril GM. Source: Clinical Chemistry. 2001 December; 47(12): 2108-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11719474

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Comparison of the cDNA and amino acid sequences of lipoprotein lipase in eight species. Author(s): Raisonnier A, Etienne J, Arnault F, Brault D, Noe L, Chuat JC, Galibert F. Source: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology. 1995 July; 111(3): 385-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7613763

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Comparison of urine trypsinogen-2 test strip with serum lipase in the diagnosis of acute pancreatitis. Author(s): Kylanpaa-Back ML, Kemppainen E, Puolakkainen P, Hedstrom J, Haapiainen R, Korvuo A, Stenman UH. Source: Hepatogastroenterology. 2002 July-August; 49(46): 1130-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12143219

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Crystal structure of human gastric lipase and model of lysosomal acid lipase, two lipolytic enzymes of medical interest. Author(s): Roussel A, Canaan S, Egloff MP, Riviere M, Dupuis L, Verger R, Cambillau C. Source: The Journal of Biological Chemistry. 1999 June 11; 274(24): 16995-7002. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10358049

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Deceptive hyperbilirubinaemia in a newborn with familial lipoprotein lipase deficiency. Author(s): Ng PC, Lam CW, Fok TF, Lee CH, Lo DY, Chan LY, Sin NC, Packard CJ. Source: Journal of Paediatrics and Child Health. 2001 June; 37(3): 314-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11468054

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Decreased activities of lipoprotein lipase and hepatic triglyceride lipase in patients with gout. Author(s): Tsutsumi Z, Yamamoto T, Moriwaki Y, Takahashi S, Hada T. Source: Metabolism: Clinical and Experimental. 2001 August; 50(8): 952-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11474484

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Deficiency of choresteryl ester transfer protein and gene polymorphisms of lipoprotein lipase and hepatic lipase are not associated with longevity. Author(s): Arai Y, Hirose N, Yamamura K, Nakazawa S, Shimizu K, Takayama M, Ebihara Y, Homma S, Gondo Y, Masui Y, Inagaki H. Source: Journal of Molecular Medicine (Berlin, Germany). 2003 February; 81(2): 102-9. Epub 2003 February 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12601526

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Detection of missense mutations in the genes for lipoprotein lipase and hepatic triglyceride lipase in patients with dyslipidemia undergoing coronary angiography. Author(s): Moennig G, Wiebusch H, Enbergs A, Dorszewski A, Kerber S, Schulte H, Vielhauer C, Haverkamp W, Assmann G, Breithardt G, Funke H. Source: Atherosclerosis. 2000 April; 149(2): 395-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10729390

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Determinants of HDL particle size in patients with the null (P207L) or defective (D9N) mutation in the lipoprotein lipase gene: the Quebec LipD Study. Author(s): Ruel IL, Gaudet D, Perron P, Pascot A, Despres JP, Bergeron J, Julien P, Lamarche B. Source: Atherosclerosis. 2002 June; 162(2): 269-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11996946

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Determination and use of haplotypes: ethnic comparison and association of the lipoprotein lipase gene and coronary artery disease in Mexican-Americans. Author(s): Goodarzi MO, Guo X, Taylor KD, Quinones MJ, Samayoa C, Yang H, Saad MF, Palotie A, Krauss RM, Hsueh WA, Rotter JI. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. 2003 July-August; 5(4): 322-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865761

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Development and evaluation of a direct sandwich-enzyme-linked immunosorbent assay for the quantification of human hepatic triglyceride lipase mass in human plasma. Author(s): Nishimura M, Ohkaru Y, Ishii H, Sunahara N, Takagi A, Ikeda Y. Source: Journal of Immunological Methods. 2000 February 21; 235(1-2): 41-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10675756

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Diabetic state induces lipid loading and altered expression and secretion of lipoprotein lipase in human monocyte-derived macrophages. Author(s): Dobrian AD, Lazar V, Sinescu C, Mincu D, Simionescu M. Source: Atherosclerosis. 2000 November; 153(1): 191-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11058715

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Dietary fat intake determines the effect of a common polymorphism in the hepatic lipase gene promoter on high-density lipoprotein metabolism: evidence of a strong dose effect in this gene-nutrient interaction in the Framingham Study. Author(s): Ordovas JM, Corella D, Demissie S, Cupples LA, Couture P, Coltell O, Wilson PW, Schaefer EJ, Tucker KL. Source: Circulation. 2002 October 29; 106(18): 2315-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12403660

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Dietary fat interacts with the -514C>T polymorphism in the hepatic lipase gene promoter on plasma lipid profiles in a multiethnic Asian population: the 1998 Singapore National Health Survey. Author(s): Tai ES, Corella D, Deurenberg-Yap M, Cutter J, Chew SK, Tan CE, Ordovas JM; Singapore National Health Survey. Source: The Journal of Nutrition. 2003 November; 133(11): 3399-408. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14608050

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Dietary fat modulates gastric lipase activity in healthy humans. Author(s): Armand M, Hamosh M, DiPalma JS, Gallagher J, Benjamin SB, Philpott JR, Lairon D, Hamosh P. Source: The American Journal of Clinical Nutrition. 1995 July; 62(1): 74-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7598069

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Difference in substrate specificity between human and mouse lysosomal acid lipase: low affinity for cholesteryl ester in mouse lysosomal acid lipase. Author(s): Groener JE, Bax W, Stuani C, Pagani F. Source: Biochimica Et Biophysica Acta. 2000 September 27; 1487(2-3): 155-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11018468

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Different reactivities of high density lipoprotein2 subfractions with hepatic lipase. Author(s): Mowri HO, Patsch W, Smith LC, Gotto AM Jr, Patsch JR. Source: Journal of Lipid Research. 1992 September; 33(9): 1269-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1402396

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Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion. Author(s): Boedeker JC, Doolittle MH, White AL. Source: Journal of Lipid Research. 2001 November; 42(11): 1858-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11714855

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Differential expression of lipoprotein lipase gene in tissues of the rat model with visceral obesity and postprandial hyperlipidemia. Author(s): Hikita M, Bujo H, Yamazaki K, Taira K, Takahashi K, Kobayashi J, Saito Y. Source: Biochemical and Biophysical Research Communications. 2000 October 22; 277(2): 423-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11032739

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Differentiation of human monocytes to monocyte-derived macrophages is associated with increased lipoprotein lipase-induced tumor necrosis factor-alpha expression and production: a process involving cell surface proteoglycans and protein kinase C. Author(s): Mamputu JC, Renier G. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1999 June; 19(6): 1405-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10364070

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Direct determination by high-performance liquid chromatography of sn-2 monopalmitin after enzymatic lipase hydrolysis. Author(s): Lopez-Lopez A, Castellote-Bargallo AI, Lopez-Sabater MC. Source: J Chromatogr B Biomed Sci Appl. 2001 August 25; 760(1): 97-105. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11522071

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Diurnal variation in lipoprotein lipase activity. Author(s): Arasaradnam MP, Morgan L, Wright J, Gama R. Source: Annals of Clinical Biochemistry. 2002 March; 39(Pt 2): 136-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11928761

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DNA polymorphisms of lipase related genes. Author(s): Cao H, Hegele RA. Source: Journal of Human Genetics. 2003; 48(8): 443-6. Epub 2003 August 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12898288

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Dose-dependent acceleration of high-density lipoprotein catabolism by endothelial lipase. Author(s): Maugeais C, Tietge UJ, Broedl UC, Marchadier D, Cain W, McCoy MG, Lund-Katz S, Glick JM, Rader DJ. Source: Circulation. 2003 October 28; 108(17): 2121-6. Epub 2003 September 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14517167

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Early prediction of aetiology and severity of acute pancreatitis by serum amylase and lipase assays. Author(s): Manes G, Rabitti PG, Laccetti M, Pacelli L, Carraturo I, Uomo G. Source: Minerva Gastroenterol Dietol. 1995 September; 41(3): 211-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8519858

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Effect of atorvastatin treatment on lipoprotein lipase mass in the pre-heparin plasma in Japanese hyperlipidemic subjects. Author(s): Kobayashi J, Maruyama T, Masuda M, Shinomiya M. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 December; 314(1-2): 261-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11718706

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Effects of a brisk walk on lipoprotein lipase activity and plasma triglyceride concentrations in the fasted and postprandial states. Author(s): Gill JM, Herd SL, Vora V, Hardman AE. Source: European Journal of Applied Physiology. 2003 April; 89(2): 184-90. Epub 2003 February 07. Erratum In: Eur J Appl Physiol. 2003 May; 89(3-4): 408. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665983

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Effects of a lipase inhibitor (Orlistat) on cholecystokinin and appetite in response to a high-fat meal. Author(s): Goedecke JH, Barsdorf M, Beglinger C, Levitt NS, Lambert EV. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2003 December; 27(12): 1479-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14634678

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Effects of low and moderate exercise intensity on postprandial lipemia and postheparin plasma lipoprotein lipase activity in physically active men. Author(s): Katsanos CS, Grandjean PW, Moffatt RJ. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2004 January; 96(1): 181-8. Epub 2003 August 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12949025

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Effects of nonlipolytic ligand function of endothelial lipase on high density lipoprotein metabolism in vivo. Author(s): Broedl UC, Maugeais C, Marchadier D, Glick JM, Rader DJ. Source: The Journal of Biological Chemistry. 2003 October 17; 278(42): 40688-93. Epub 2003 August 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909635

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Effects of orlistat, a lipase inhibitor, on the pharmacokinetics of three highly lipophilic drugs (amiodarone, fluoxetine, and simvastatin) in healthy volunteers. Author(s): Zhi J, Moore R, Kanitra L, Mulligan TE. Source: Journal of Clinical Pharmacology. 2003 April; 43(4): 428-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12723464

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Effects of plasma adrenaline on hormone-sensitive lipase at rest and during moderate exercise in human skeletal muscle. Author(s): Watt MJ, Stellingwerff T, Heigenhauser GJ, Spriet LL. Source: The Journal of Physiology. 2003 July 1; 550(Pt 1): 325-32. Epub 2003 May 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12730334

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Effects of plasma apolipoproteins on lipoprotein lipase-mediated lipolysis of small and large lipid emulsions. Author(s): Yamamoto M, Morita SY, Kumon M, Kawabe M, Nishitsuji K, Saito H, Vertut-Doi A, Nakano M, Handa T. Source: Biochimica Et Biophysica Acta. 2003 June 10; 1632(1-3): 31-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12782148

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Effects of sphingomyelin on apolipoprotein E- and lipoprotein lipase-mediated cell uptake of lipid particles. Author(s): Morita SY, Okuhira K, Tsuchimoto N, Vertut-Doi A, Saito H, Nakano M, Handa T. Source: Biochimica Et Biophysica Acta. 2003 March 17; 1631(2): 169-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12633683

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Effects of the hepatic lipase gene and physical activity on coronary heart disease risk. Author(s): Hokanson JE, Kamboh MI, Scarboro S, Eckel RH, Hamman RF. Source: American Journal of Epidemiology. 2003 November 1; 158(9): 836-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585761

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Effects on lipoprotein subclasses of combined expression of human hepatic lipase and human apoB in transgenic rabbits. Author(s): Rizzo M, Taylor JM, Barbagallo CM, Berneis K, Blanche PJ, Krauss RM. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2004 January; 24(1): 141-6. Epub 2003 November 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615390

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Enhanced lipoprotein lipase secretion and foam cell formation by macrophages of patients with growth hormone deficiency: possible contribution to increased risk of atherogenesis? Author(s): Serri O, Li L, Maingrette F, Jaffry N, Renier G. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 February; 89(2): 979-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14764824

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Evidence that hepatic lipase and endothelial lipase have different substrate specificities for high-density lipoprotein phospholipids. Author(s): Duong M, Psaltis M, Rader DJ, Marchadier D, Barter PJ, Rye KA. Source: Biochemistry. 2003 November 25; 42(46): 13778-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622025

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Evidence that reduced lipoprotein lipase activity is not a primary pathogenetic factor for hypertriglyceridemia in renal failure. Author(s): Arnadottir M, Thysell H, Dallongeville J, Fruchart JC, Nilsson-Ehle P. Source: Kidney International. 1995 September; 48(3): 779-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7474664

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Exaggerated postprandial lipaemia and lower post-heparin lipoprotein lipase activity in middle-aged men. Author(s): Jackson KG, Knapper-Francis JM, Morgan LM, Webb DH, Zampelas A, Williams CM. Source: Clinical Science (London, England : 1979). 2003 October; 105(4): 457-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12812518

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Expression analysis of the Candida albicans lipase gene family during experimental infections and in patient samples. Author(s): Stehr F, Felk A, Gacser A, Kretschmar M, Mahnss B, Neuber K, Hube B, Schafer W. Source: Fems Yeast Research. 2004 January; 4(4-5): 401-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14734020

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Expression of human hepatic lipase in the rabbit model preferentially enhances the clearance of triglyceride-enriched versus native high-density lipoprotein apolipoprotein A-I. Author(s): Rashid S, Trinh DK, Uffelman KD, Cohn JS, Rader DJ, Lewis GF. Source: Circulation. 2003 June 24; 107(24): 3066-72. Epub 2003 Jun 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796142

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Factors affecting lipoprotein lipase in hypertensive patients. Author(s): Marotta T, Ferrara LA, Di Marino L, Mancini M, Annuzzi G, Russo O, D'Orta G, Lucarelli C, Rossi F. Source: Metabolism: Clinical and Experimental. 1995 June; 44(6): 712-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7783654

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Faecal immunoreactive lipase: a simple diagnostic test for cystic fibrosis. Author(s): Munch R, Bragger CP, Altorfer J, Hoppe B, Shmerling DH, Ammann R. Source: European Journal of Pediatrics. 1998 April; 157(4): 282-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9578961

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Familial combined hyperlipidemia and abnormal lipoprotein lipase. Author(s): Babirak SP, Brown BG, Brunzell JD. Source: Arterioscler Thromb. 1992 October; 12(10): 1176-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1390589

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Familial lipoprotein lipase (LPL) deficiency: a catalogue of LPL gene mutations identified in 20 patients from the UK, Sweden, and Italy. Author(s): Mailly F, Palmen J, Muller DP, Gibbs T, Lloyd J, Brunzell J, Durrington P, Mitropoulos K, Betteridge J, Watts G, Lithell H, Angelico F, Humphries SE, Talmud PJ. Source: Human Mutation. 1997; 10(6): 465-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9401010

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Familial lipoprotein lipase deficiency in infancy: clinical, biochemical, and molecular study. Author(s): Feoli-Fonseca JC, Levy E, Godard M, Lambert M. Source: The Journal of Pediatrics. 1998 September; 133(3): 417-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9738727

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Family study of lipoprotein lipase gene polymorphisms and plasma triglyceride levels. Author(s): Georges JL, Regis-Bailly A, Salah D, Rakotovao R, Siest G, Visvikis S, Tiret L. Source: Genetic Epidemiology. 1996; 13(2): 179-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8722745

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Fat intake and food choices during weight reduction with diet, behavioural modification and a lipase inhibitor. Author(s): Franson K, Rossner S. Source: Journal of Internal Medicine. 2000 May; 247(5): 607-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10810001

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Fatty acid and positional selectivities of gastric lipase from premature human infants: in vitro studies. Author(s): Jensen RG, deJong FA, Lambert-Davis LG, Hamosh M. Source: Lipids. 1994 June; 29(6): 433-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8090065

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Fatty acid specificity of hormone-sensitive lipase. Implication in the selective hydrolysis of triacylglycerols. Author(s): Raclot T, Holm C, Langin D. Source: Journal of Lipid Research. 2001 December; 42(12): 2049-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11734578

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Fatty acids liberated from high-density lipoprotein phospholipids by endothelialderived lipase are incorporated into lipids in HepG2 cells. Author(s): Strauss JG, Hayn M, Zechner R, Levak-Frank S, Frank S. Source: The Biochemical Journal. 2003 May 1; 371(Pt 3): 981-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12553881

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Fecal immunoreactive lipase, a simple diagnostic test for cystic fibrosis. Author(s): Shmerling DH. Source: European Journal of Pediatrics. 1999 April; 158(4): 339. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10206136

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Ferrocenylnaphthalene diimide-based electrochemical hybridization assay for a heterozygous deficiency of the lipoprotein lipase gene. Author(s): Yamashita K, Takagi A, Takagi M, Kondo H, Ikeda Y, Takenaka S. Source: Bioconjugate Chemistry. 2002 November-December; 13(6): 1193-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12440853

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Food deprivation increases post-heparin lipoprotein lipase activity in humans. Author(s): Ruge T, Svensson A, Eriksson JW, Olivecrona T, Olivecrona G. Source: European Journal of Clinical Investigation. 2001 December; 31(12): 1040-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903489

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Fourier-transform infrared assay of bile salt-stimulated lipase activity in reversed micelles. Author(s): O'Connor CJ, Cleverly DR. Source: Journal of Chemical Technology and Biotechnology (Oxford, Oxfordshire : 1986). 1994 November; 61(3): 209-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7527225

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Frequency and allelic association of common variants in the lipoprotein lipase gene in different ethnic groups: the Wandsworth Heart and Stroke Study. Author(s): Hall S, Talmud PJ, Cook DG, Wicks PD, Rothwell MJ, Strazzullo P, Sagnella GA, Cappuccio FP. Source: Genetic Epidemiology. 2000 March; 18(3): 203-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10723106

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Functional analyses of human apolipoprotein CII by site-directed mutagenesis: identification of residues important for activation of lipoprotein lipase. Author(s): Shen Y, Lookene A, Nilsson S, Olivecrona G. Source: The Journal of Biological Chemistry. 2002 February 8; 277(6): 4334-42. Epub 2001 November 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11719505

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Functional characterization of 4 polymorphisms in promoter region of hepatic lipase gene. Author(s): van't Hooft FM, Lundahl B, Ragogna F, Karpe F, Olivecrona G, Hamsten A. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 May; 20(5): 1335-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10807751

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Functional characterization of a chimeric lipase genetically engineered from human lipoprotein lipase and human hepatic lipase. Author(s): Dichek HL, Parrott C, Ronan R, Brunzell JD, Brewer HB Jr, Santamarina-Fojo S. Source: Journal of Lipid Research. 1993 August; 34(8): 1393-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8409770

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Functional role of N-linked glycosylation in human hepatic lipase: asparagine-56 is important for both enzyme activity and secretion. Author(s): Wolle J, Jansen H, Smith LC, Chan L. Source: Journal of Lipid Research. 1993 December; 34(12): 2169-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8301235

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Functional variants in the lipoprotein lipase gene and risk cardiovascular disease. Author(s): Hokanson JE. Source: Current Opinion in Lipidology. 1999 October; 10(5): 393-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10554701

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G-250A substitution in promoter of hepatic lipase gene is associated with dyslipidemia and insulin resistance in healthy control subjects and in members of families with familial combined hyperlipidemia. Author(s): Pihlajamaki J, Karjalainen L, Karhapaa P, Vauhkonen I, Taskinen MR, Deeb SS, Laakso M. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 July; 20(7): 1789-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10894818

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Gastric lipase secretion after sham feeding and cholinergic blockade. Author(s): Wojdemann M, Olsen O, Norregaard P, Sternby B, Rehfeld JF. Source: Digestive Diseases and Sciences. 1997 May; 42(5): 1070-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9149064

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Gastric lipase: crystal structure and activity. Author(s): Canaan S, Roussel A, Verger R, Cambillau C. Source: Biochimica Et Biophysica Acta. 1999 November 23; 1441(2-3): 197-204. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10570247

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Gender differences in the effect of type 2 diabetes on serum lipids, pre-heparin plasma lipoprotein lipase mass and other metabolic parameters in Japanese population. Author(s): Kobayashi J, Maruyama T, Watanabe H, Kudoh A, Tateishi S, Sasaki T, Murano S, Watanabe M. Source: Diabetes Research and Clinical Practice. 2003 October; 62(1): 39-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581156

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Gender specific associations of the Trp64Arg mutation in the beta3-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation. Author(s): Corella D, Guillen M, Portoles O, Sorli JV, Alonso V, Folch J, Saiz C. Source: Journal of Internal Medicine. 2001 October; 250(4): 348-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11576322

Studies

97

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Gender-related association between the -93T-->G/D9N haplotype of the lipoprotein lipase gene and elevated lipid levels in familial combined hyperlipidemia. Author(s): Hoffer MJ, Bredie SJ, Snieder H, Reymer PW, Demacker PN, Havekes LM, Boomsma DI, Stalenhoef AF, Frants RR, Kastelein JJ. Source: Atherosclerosis. 1998 May; 138(1): 91-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9678774

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Genetic polymorphisms and mutations of the lipoprotein lipase gene in Japanese schoolchildren with hypoalphalipoproteinemia. Author(s): Yamana K, Yanagi H, Hirano C, Kobayashi K, Tanaka M, Tomura S, Tsuchiya S, Hamaguchi H. Source: J Atheroscler Thromb. 1998; 4(3): 97-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9730139

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Genetic polymorphisms of hepatic lipase and cholesteryl ester transfer protein, intermediate phenotypes, and coronary risk: do they add up yet? Author(s): Anderson JL, Carlquist JF. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 1990-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798570

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Genetic screening of the lipoprotein lipase gene for mutations associated with high triglyceride/low HDL-cholesterol levels. Author(s): Razzaghi H, Aston CE, Hamman RF, Kamboh MI. Source: Human Genetics. 2000 September; 107(3): 257-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11071388

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Genetic study of common variants at the Apo E, Apo AI, Apo CIII, Apo B, lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes and coronary artery disease (CAD): variation in LIPC gene associates with clinical outcomes in patients with established CAD. Author(s): Baroni MG, Berni A, Romeo S, Arca M, Tesorio T, Sorropago G, Di Mario U, Galton DJ. Source: Bmc Medical Genetics [electronic Resource]. 2003 September 10; 4(1): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12964943

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Genetic underpinnings of LDL size and density: a role for hepatic lipase? Author(s): Havel RJ. Source: The American Journal of Clinical Nutrition. 2000 June; 71(6): 1390-1. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10837276

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Genetic variant showing a positive interaction with beta-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients. The Ser447-stop substitution in the lipoprotein lipase gene. REGRESS Study Group. Author(s): Groenemeijer BE, Hallman MD, Reymer PW, Gagne E, Kuivenhoven JA, Bruin T, Jansen H, Lie KI, Bruschke AV, Boerwinkle E, Hayden MR, Kastelein JJ. Source: Circulation. 1997 June 17; 95(12): 2628-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9193431

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Genetic variation at the lipoprotein lipase locus and plasma lipoprotein and insulin levels in the Quebec Family Study. Author(s): Ukkola O, Garenc C, Perusse L, Bergeron J, Despres JP, Rao DC, Bouchard C. Source: Atherosclerosis. 2001 September; 158(1): 199-206. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11500192

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Genetic variations of the hepatic lipase gene in Korean patients with coronary artery disease. Author(s): Hong SH, Song J, Kim JQ. Source: Clinical Biochemistry. 2000 June; 33(4): 291-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936588

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Genetics of the lipoprotein lipase gene and hypertriglyceridaemia. Author(s): McDonnell MG, Young IS, Nicholls DP, Archbold GP, Graham CA. Source: British Journal of Biomedical Science. 2003; 60(2): 84-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12866915

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GH but not IGF-I or insulin increases lipoprotein lipase activity in muscle tissues of hypophysectomised rats. Author(s): Oscarsson J, Ottosson M, Vikman-Adolfsson K, Frick F, Enerback S, Lithell H, Eden S. Source: The Journal of Endocrinology. 1999 February; 160(2): 247-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9924194

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Global structure and dynamics of human apolipoprotein CII in complex with micelles: evidence for increased mobility of the helix involved in the activation of lipoprotein lipase. Author(s): Zdunek J, Martinez GV, Schleucher J, Lycksell PO, Yin Y, Nilsson S, Shen Y, Olivecrona G, Wijmenga S. Source: Biochemistry. 2003 February 25; 42(7): 1872-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12590574

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99

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Glucose ingestion blunts hormone-sensitive lipase activity in contracting human skeletal muscle. Author(s): Watt MJ, Krustrup P, Secher NH, Saltin B, Pedersen BK, Febbraio MA. Source: American Journal of Physiology. Endocrinology and Metabolism. 2004 January; 286(1): E144-50. Epub 2003 September 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506077

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Glycerol interference in serum lipase assay falsely indicates pancreas injury. Author(s): Bilodeau L, Grotte DA, Preese LM, Apple FS. Source: Gastroenterology. 1992 September; 103(3): 1066-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1499907

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Glycosylation of bile salt-dependent lipase (cholesterol esterase). Author(s): Mas E, Sadoulet MO, el Battari A, Lombardo D. Source: Methods Enzymol. 1997; 284: 340-53. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9379944

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HDL regulates the displacement of hepatic lipase from cell surface proteoglycans and the hydrolysis of VLDL triacylglycerol. Author(s): Ramsamy TA, Boucher J, Brown RJ, Yao Z, Sparks DL. Source: Journal of Lipid Research. 2003 April; 44(4): 733-41. Epub 2003 January 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562872

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Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet. Author(s): Deeb SS, Zambon A, Carr MC, Ayyobi AF, Brunzell JD. Source: Journal of Lipid Research. 2003 July; 44(7): 1279-86. Epub 2003 March 16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12639974

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Hepatic lipase C-480T polymorphism modifies the effect of HDL cholesterol on the risk of acute myocardial infarction in men: a prospective population based study. Author(s): Fan YM, Salonen JT, Koivu TA, Tuomainen TP, Nyyssonen K, Lakka TA, Salonen R, Seppanen K, Nikkari ST, Tahvanainen E, Lehtimaki T. Source: Journal of Medical Genetics. 2004 March; 41(3): E28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14985399

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Hepatic lipase C514T polymorphism and its relationship with plasma HDL-C levels and coronary artery disease in Koreans. Author(s): Park KW, Choi JH, Chae IH, Cho HJ, Oh S, Kim HS, Lee MM, Park YB, Choi YS. Source: J Biochem Mol Biol. 2003 March 31; 36(2): 237-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12689525

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Hepatic lipase genotype, diabetes risk, and implications for preventative medicine. Author(s): Shuldiner AR, Hoppman N, Pollin TI. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 May; 89(5): 2015-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15126513

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Hepatic lipase mediates an increase in selective uptake of HDL-associated cholesteryl esters by cells in culture independent from SR-BI. Author(s): Brundert M, Heeren J, Greten H, Rinninger F. Source: Journal of Lipid Research. 2003 May; 44(5): 1020-32. Epub 2003 March 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611911

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Hepatic lipase mutation may reduce vascular disease prevalence in hemodialysis patients with high CETP levels. Author(s): Kimura H, Miyazaki R, Imura T, Masunaga S, Suzuki S, Gejyo F, Yoshida H. Source: Kidney International. 2003 November; 64(5): 1829-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531818

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Hepatic lipase mutations,elevated high-density lipoprotein cholesterol, and increased risk of ischemic heart disease: the Copenhagen City Heart Study. Author(s): Andersen RV, Wittrup HH, Tybjaerg-Hansen A, Steffensen R, Schnohr P, Nordestgaard BG. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 1972-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798568

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Hepatic lipase promoter C-514T polymorphism influences serial changes in HDL cholesterol levels since childhood: the Bogalusa Heart Study. Author(s): Chen W, Srinivasan SR, Boerwinkle E, Berenson GS; Bogalusa Heart Study. Source: Atherosclerosis. 2003 July; 169(1): 175-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860265

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Hepatic lipase promotes the selective uptake of high density lipoprotein-cholesteryl esters via the scavenger receptor B1. Author(s): Lambert G, Chase MB, Dugi K, Bensadoun A, Brewer HB Jr, SantamarinaFojo S. Source: Journal of Lipid Research. 1999 July; 40(7): 1294-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10393214

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Hepatic lipase: a marker for cardiovascular disease risk and response to therapy. Author(s): Zambon A, Deeb SS, Pauletto P, Crepaldi G, Brunzell JD. Source: Current Opinion in Lipidology. 2003 April; 14(2): 179-89. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12642787

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Hepatic lipase: a pro- or anti-atherogenic protein? Author(s): Jansen H, Verhoeven AJ, Sijbrands EJ. Source: Journal of Lipid Research. 2002 September; 43(9): 1352-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235167

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Hepatic lipase: structure/function relationship, synthesis, and regulation. Author(s): Perret B, Mabile L, Martinez L, Terce F, Barbaras R, Collet X. Source: Journal of Lipid Research. 2002 August; 43(8): 1163-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12177160

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Hepatic triglyceride lipase promotes low density lipoprotein receptor-mediated catabolism of very low density lipoproteins in vitro. Author(s): Medh JD, Bowen SL, Fry GL, Ruben S, Hill J, Wong H, Chappell DA. Source: Journal of Lipid Research. 1999 July; 40(7): 1263-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10393211

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High-density lipoprotein-cholesterol, its subfractions, and responses to exercise training are dependent on endothelial lipase genotype. Author(s): Halverstadt A, Phares DA, Ferrell RE, Wilund KR, Goldberg AP, Hagberg JM. Source: Metabolism: Clinical and Experimental. 2003 November; 52(11): 1505-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624415

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Hormone-sensitive lipase activity and fatty acyl-CoA content in human skeletal muscle during prolonged exercise. Author(s): Watt MJ, Heigenhauser GJ, O'Neill M, Spriet LL. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 July; 95(1): 314-21. Epub 2003 February 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611761

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Hormone-sensitive lipase in skeletal muscle: regulatory mechanisms. Author(s): Langfort J, Donsmark M, Ploug T, Holm C, Galbo H. Source: Acta Physiologica Scandinavica. 2003 August; 178(4): 397-403. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12864745

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Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis. Author(s): Kraemer FB, Shen WJ. Source: Journal of Lipid Research. 2002 October; 43(10): 1585-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12364542

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Hormone-sensitive lipase--new roles for an old enzyme. Author(s): Yeaman SJ. Source: The Biochemical Journal. 2004 April 1; 379(Pt 1): 11-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14725507

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Human hepatic and lipoprotein lipase: the loop covering the catalytic site mediates lipase substrate specificity. Author(s): Dugi KA, Dichek HL, Santamarina-Fojo S. Source: The Journal of Biological Chemistry. 1995 October 27; 270(43): 25396-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7592706

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Identification of a lipoprotein lipase cofactor-binding site by chemical cross-linking and transfer of apolipoprotein C-II-responsive lipolysis from lipoprotein lipase to hepatic lipase. Author(s): McIlhargey TL, Yang Y, Wong H, Hill JS. Source: The Journal of Biological Chemistry. 2003 June 20; 278(25): 23027-35. Epub 2003 April 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12682050

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Identification of a novel lipase gene mutated in lpd mice with hypertriglyceridemia and associated with dyslipidemia in humans. Author(s): Wen XY, Hegele RA, Wang J, Wang DY, Cheung J, Wilson M, Yahyapour M, Bai Y, Zhuang L, Skaug J, Young TK, Connelly PW, Koop BF, Tsui LC, Stewart AK. Source: Human Molecular Genetics. 2003 May 15; 12(10): 1131-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12719377

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Identification of functional prolactin (PRL) receptor gene expression: PRL inhibits lipoprotein lipase activity in human white adipose tissue. Author(s): Ling C, Svensson L, Oden B, Weijdegard B, Eden B, Eden S, Billig H. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 1804-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12679477

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Identification of genetic variants in endothelial lipase in persons with elevated highdensity lipoprotein cholesterol. Author(s): deLemos AS, Wolfe ML, Long CJ, Sivapackianathan R, Rader DJ. Source: Circulation. 2002 September 10; 106(11): 1321-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221047

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Immunohistochemical localization of endothelial cell-derived lipase in atherosclerotic human coronary arteries. Author(s): Azumi H, Hirata K, Ishida T, Kojima Y, Rikitake Y, Takeuchi S, Inoue N, Kawashima S, Hayashi Y, Itoh H, Quertermous T, Yokoyama M. Source: Cardiovascular Research. 2003 June 1; 58(3): 647-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798438

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In vitro lipolysis by human pancreatic lipase is specifically abolished by its inactive forms. Author(s): Miled N, Berti-Dupuis L, Riviere M, Carriere F, Verger R. Source: Biochimica Et Biophysica Acta. 2003 February 21; 1645(2): 241-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12573254

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Increased circulating malondialdehyde-modified LDL in the patients with familial combined hyperlipidemia and its relation with the hepatic lipase activity. Author(s): Yamazaki K, Bujo H, Taira K, Itou N, Shibasaki M, Takahashi K, Saito Y. Source: Atherosclerosis. 2004 January; 172(1): 181-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14709374

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Increased expression of lipoprotein lipase in transgenic rabbits does not lead to abnormalities in skeletal and heart muscles. Author(s): Koike T, Wang X, Unoki H, Liang J, Ichikawa T, Kitajima S, Watanabe T, Fan J. Source: Muscle & Nerve. 2002 December; 26(6): 823-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12451608

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Indinavir inhibits sterol-regulatory element-binding protein-1c-dependent lipoprotein lipase and fatty acid synthase gene activations. Author(s): Miserez AR, Muller PY, Spaniol V. Source: Aids (London, England). 2002 August 16; 16(12): 1587-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12172079

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Influence of lipoprotein lipase serine 447 stop polymorphism on tracking of triglycerides and HDL cholesterol from childhood to adulthood and familial risk of coronary artery disease: the Bogalusa heart study. Author(s): Chen W, Srinivasan SR, Elkasabany A, Ellsworth DL, Boerwinkle E, Berenson GS. Source: Atherosclerosis. 2001 December; 159(2): 367-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11730816

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Inhibition of endothelial lipase causes increased HDL cholesterol levels in vivo. Author(s): Jin W, Millar JS, Broedl U, Glick JM, Rader DJ. Source: The Journal of Clinical Investigation. 2003 February; 111(3): 357-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12569161

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Inhibition of lipase activity in antibiotic-resistant propionibacterium acnes strains. Author(s): Gloor M, Wasik B, Becker A, Hoffler U. Source: Dermatology (Basel, Switzerland). 2002; 205(3): 260-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12399674

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Inhibitory effect of the pancreatic lipase C-terminal domain on intestinal lipolysis in rats fed a high-fat diet: chronic study. Author(s): Sebban-Kreuzer C, Ayvazian L, Juhel C, Salles JP, Chapus C, Kerfelec B. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2003 March; 27(3): 319-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12629558

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Inhibitory effects of human and porcine alpha-amylase on CCK-8-stimulated lipase secretion of isolated rat pancreatic acini. Author(s): Jonas L, Mikkat U, Lehmann R, Schareck W, Walzel H, Schroder W, Lopp H, Pussa T, Toomik P. Source: Pancreatology : Official Journal of the International Association of Pancreatology (Iap). [et Al.]. 2003; 3(4): 342-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890998

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Interaction effect of Serine447Stop variant of the lipoprotein lipase gene and C-514T variant of the hepatic lipase gene on serum triglyceride levels in young adults: the Bogalusa Heart Study. Author(s): Xin X, Srinivasan SR, Chen W, Boerwinkle E, Berenson GS. Source: Metabolism: Clinical and Experimental. 2003 October; 52(10): 1337-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14564687

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Interaction of the lipoprotein lipase asparagine 291-->serine mutation with body mass index determines elevated plasma triacylglycerol concentrations: a study in hyperlipidemic subjects, myocardial infarction survivors, and healthy adults. Author(s): Fisher RM, Mailly F, Peacock RE, Hamsten A, Seed M, Yudkin JS, Beisiegel U, Feussner G, Miller G, Humphries SE, et al. Source: Journal of Lipid Research. 1995 October; 36(10): 2104-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8576637

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Interfacial binding of human gastric lipase to lipid monolayers, measured with an ELISA. Author(s): Aoubala M, Ivanova M, Douchet I, De Caro A, Verger R. Source: Biochemistry. 1995 August 29; 34(34): 10786-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7545008

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Involvement of a cGMP-dependent pathway in the natriuretic peptide-mediated hormone-sensitive lipase phosphorylation in human adipocytes. Author(s): Sengenes C, Bouloumie A, Hauner H, Berlan M, Busse R, Lafontan M, Galitzky J. Source: The Journal of Biological Chemistry. 2003 December 5; 278(49): 48617-26. Epub 2003 September 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970365

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Is blockade of pancreatic lipase the answer? Author(s): Halsted CH. Source: The American Journal of Clinical Nutrition. 1999 June; 69(6): 1059-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10357720

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Isolation and characterization of human milk bile salt-activated lipase C-tail fragment. Author(s): Wang CS, Dashti A, Jackson KW, Yeh JC, Cummings RD, Tang J. Source: Biochemistry. 1995 August 22; 34(33): 10639-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7654718

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Kinetic behavior of the pancreatic lipase-colipase-lipid system. Author(s): Brockman HL. Source: Biochimie. 2000 November; 82(11): 987-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11099795

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Kinetic behaviour of pancreatic lipase in five species using emulsions and monomolecular films of synthetic glycerides. Author(s): Gargouri Y, Bensalah A, Douchet I, Verger R. Source: Biochimica Et Biophysica Acta. 1995 August 3; 1257(3): 223-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7647098

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Kinetics of in vitro lipolysis of human very low-density lipoprotein by lipoprotein lipase. Author(s): Schreier L, Berg G, Zago V, Gonzalez AI, Wikinski R. Source: Nutr Metab Cardiovasc Dis. 2002 February; 12(1): 13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12125224

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Kinetics of lipolysis of very low density lipoproteins by lipoprotein lipase. Importance of particle number and noncompetitive inhibition by particles with low triglyceride content. Author(s): Connelly PW, Maguire GF, Vezina C, Hegele RA, Kuksis A. Source: The Journal of Biological Chemistry. 1994 August 12; 269(32): 20554-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8051155

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Lack of association of lipoprotein lipase gene polymorphisms with coronary artery disease in the Saudi Arab population. Author(s): Abu-Amero KK, Wyngaard CA, Al-Boudari OM, Kambouris M, Dzimiri N. Source: Archives of Pathology & Laboratory Medicine. 2003 May; 127(5): 597-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12708905

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Lectin-like Ox-LDL receptor is expressed in human INT-407 intestinal cells: involvement in the transcytosis of pancreatic bile salt-dependent lipase. Author(s): Bruneau N, Richard S, Silvy F, Verine A, Lombardo D. Source: Molecular Biology of the Cell. 2003 July; 14(7): 2861-75. Epub 2003 April 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12857870

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Leptin increases lipoprotein lipase secretion by macrophages: involvement of oxidative stress and protein kinase C. Author(s): Maingrette F, Renier G. Source: Diabetes. 2003 August; 52(8): 2121-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12882931

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Letting lipids go: hormone-sensitive lipase. Author(s): Haemmerle G, Zimmermann R, Zechner R. Source: Current Opinion in Lipidology. 2003 June; 14(3): 289-97. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12840660

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Lipase inhibition attenuates the acute inhibitory effects of oral fat on food intake in healthy subjects. Author(s): O'Donovan D, Feinle-Bisset C, Wishart J, Horowitz M. Source: The British Journal of Nutrition. 2003 November; 90(5): 849-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14667178

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Lipase inhibition by orlistat: effects on gall-bladder kinetics and cholecystokinin release in obesity. Author(s): Mathus-Vliegen EM, Van Ierland-Van Leeuwen ML, Terpstra A. Source: Alimentary Pharmacology & Therapeutics. 2004 March 1; 19(5): 601-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14987329

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Lipolysis: more than just a lipase. Author(s): Birnbaum MJ. Source: The Journal of Cell Biology. 2003 June 23; 161(6): 1011-2. Epub 2003 Jun 16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810703

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Lipoprotein lipase (LPL) gene variation and progression of carotid artery plaque. Author(s): Spence JD, Ban MR, Hegele RA. Source: Stroke; a Journal of Cerebral Circulation. 2003 May; 34(5): 1176-80. Epub 2003 April 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12690214

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Lipoprotein lipase activity and common gene variants in severely hypertriglyceridemic patients with and without diabetes. Author(s): Chadarevian R, Foubert L, Beucler I, Kottler ML, Raisonnier A, Ajlouni A, Giral P, Turpin G, Bruckert E. Source: Hormone Research. 2003; 60(2): 61-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12876415

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Lipoprotein lipase and hepatic lipase: their relationship with HDL subspecies Lp(A-I) and Lp(A-I,A-II). Author(s): Cheung MC, Sibley SD, Palmer JP, Oram JF, Brunzell JD. Source: Journal of Lipid Research. 2003 August; 44(8): 1552-8. Epub 2003 June 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12777470

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Lipoprotein lipase during heparin infusion: lower activity in hemodialysis patients. Author(s): Nasstrom B, Olivecrona G, Olivecrona T, Stegmayr BG. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 2003; 63(1): 45-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12729069

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Lipoprotein lipase gene is in linkage with blood pressure phenotypes in Chinese pedigrees. Author(s): Yang W, Huang J, Ge D, Yao C, Duan X, Shen Y, Qiang B, Gu D. Source: Human Genetics. 2004 June; 115(1): 8-12. Epub 2004 May 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15127290

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Lipoprotein lipase gene polymorphisms in Croatian patients with coronary artery disease. Author(s): Ferencak G, Pasalic D, Grskovic B, Cheng S, Fijal B, Sesto M, Skodlar J, Rukavina AS. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2003 April; 41(4): 541-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12747600

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Lipoprotein lipase gene variants and progression of nephropathy in hypercholesterolaemic patients with type 2 diabetes. Author(s): Solini A, Passaro A, Fioretto P, Nannipieri M, Ferrannini E. Source: Journal of Internal Medicine. 2004 July; 256(1): 30-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15189363

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Lipoprotein lipase gene variants and the effect of environmental factors on cardiovascular disease risk. Author(s): Talmud PJ, Stephens JW. Source: Diabetes, Obesity & Metabolism. 2004 January; 6(1): 1-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14686956

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Lipoprotein lipase is a gene for insulin resistance in Mexican Americans. Author(s): Goodarzi MO, Guo X, Taylor KD, Quinones MJ, Saad MF, Yang H, Hsueh WA, Rotter JI. Source: Diabetes. 2004 January; 53(1): 214-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14693718

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Lipoprotein lipase protects bovine endothelial cells from human NK cytotoxic activity. Author(s): De Sanctis JB, Arciniegas E, Bianco NE. Source: Cellular Immunology. 2004 January; 227(1): 59-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15051515

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Lipoprotein metabolism in subjects with hepatic lipase deficiency. Author(s): Tilly-Kiesi M, Schaefer EJ, Knudsen P, Welty FK, Dolnikowski GG, Taskinen MR, Lichtenstein AH. Source: Metabolism: Clinical and Experimental. 2004 April; 53(4): 520-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15045702

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Liver receptor homolog 1 controls the expression of carboxyl ester lipase. Author(s): Fayard E, Schoonjans K, Annicotte JS, Auwerx J. Source: The Journal of Biological Chemistry. 2003 September 12; 278(37): 35725-31. Epub 2003 July 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853459

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Macrophage-specific expression of human lipoprotein lipase accelerates atherosclerosis in transgenic apolipoprotein e knockout mice but not in C57BL/6 mice. Author(s): Wilson K, Fry GL, Chappell DA, Sigmund CD, Medh JD. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2001 November; 21(11): 1809-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11701470

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Mapping of the epitope on lipoprotein lipase recognized by a monoclonal antibody (5D2) which inhibits lipase activity. Author(s): Liu MS, Ma Y, Hayden MR, Brunzell JD. Source: Biochimica Et Biophysica Acta. 1992 September 22; 1128(1): 113-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1382603

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Maturation of hepatic lipase. Formation of functional enzyme in the endoplasmic reticulum is the rate-limiting step in its secretion. Author(s): Ben-Zeev O, Doolittle MH. Source: The Journal of Biological Chemistry. 2004 February 13; 279(7): 6171-81. Epub 2003 November 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14630921

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Measurement of the serum lipoprotein lipase concentration is useful for studying triglyceride metabolism: Comparison with postheparin plasma. Author(s): Hirano T, Nishioka F, Murakami T. Source: Metabolism: Clinical and Experimental. 2004 April; 53(4): 526-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15045703

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Mechanisms of HDL lowering in insulin resistant, hypertriglyceridemic states: the combined effect of HDL triglyceride enrichment and elevated hepatic lipase activity. Author(s): Rashid S, Watanabe T, Sakaue T, Lewis GF. Source: Clinical Biochemistry. 2003 September; 36(6): 421-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12951168

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Metabolic and genetic determinants of HDL metabolism and hepatic lipase activity in normolipidemic females. Author(s): De Oliveira e Silva ER, Kong M, Han Z, Starr C, Kass EM, Juo SH, Foster D, Dansky HM, Merkel M, Cundey K, Brinton EA, Breslow JL, Smith JD. Source: Journal of Lipid Research. 1999 July; 40(7): 1211-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10393206

110

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Metabolic characteristics of a human hepatoma cell line stably transfected with hormone-sensitive lipase. Author(s): Pease RJ, Wiggins D, Saggerson ED, Tree J, Gibbons GF. Source: The Biochemical Journal. 1999 July 15; 341 ( Pt 2): 453-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10393105

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Metabolism of apoA-I as lipid-free protein or as component of discoidal and spherical reconstituted HDLs: studies in wild-type and hepatic lipase transgenic rabbits. Author(s): Kee P, Rye KA, Taylor JL, Barrett PH, Barter PJ. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 November 1; 22(11): 1912-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12426224

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Metabolism of chylomicron-like emulsions in carriers of the S447X lipoprotein lipase polymorphism. Author(s): Almeida KA, Schreiber R, Amancio RF, Bydlowski SP, Debes-Bravo A, Issa JS, Strunz CM, Maranhao RC. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 September; 335(1-2): 157-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927697

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Mice expressing only covalent dimeric heparin binding-deficient lipoprotein lipase: muscles inefficiently secrete dimeric enzyme. Author(s): Lutz EP, Kako Y, Yagyu H, Heeren J, Marks S, Wright T, Melford K, BenZeev O, Radner H, Merkel M, Bensadoun A, Wong H, Goldberg IJ. Source: The Journal of Biological Chemistry. 2004 January 2; 279(1): 238-44. Epub 2003 October 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570890

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Mismatch PCR: a rapid method to screen for the Pro207-->Leu mutation in the lipoprotein lipase (LPL) gene. Author(s): Bijvoet SM, Hayden MR. Source: Human Molecular Genetics. 1992 October; 1(7): 541. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1307255

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Missense mutations in exon 5 of the human lipoprotein lipase gene. Inactivation correlates with loss of dimerization. Author(s): Hata A, Ridinger DN, Sutherland SD, Emi M, Kwong LK, Shuhua J, Lubbers A, Guy-Grand B, Basdevant A, Iverius PH, et al. Source: The Journal of Biological Chemistry. 1992 October 5; 267(28): 20132-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1400331

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111

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Moderate hyperalphalipoproteinaemia in a Brazilian population is related to lipoprotein lipase activity, apolipoprotein A-I concentration, age and body mass index. Author(s): Alarcon SB, Oliveira HC, Harada LM, Nunes VS, Kaplan D, Quintao EC, de Faria EC. Source: Clinical Science (London, England : 1979). 2004 January; 106(1): 11-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12889988

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Molecular cloning and characterization of the mouse carboxyl ester lipase gene and evidence for expression in the lactating mammary gland. Author(s): Lidmer AS, Kannius M, Lundberg L, Bjursell G, Nilsson J. Source: Genomics. 1995 September 1; 29(1): 115-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8530060

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Muscle-specific overexpression of lipoprotein lipase causes a severe myopathy characterized by proliferation of mitochondria and peroxisomes in transgenic mice. Author(s): Levak-Frank S, Radner H, Walsh A, Stollberger R, Knipping G, Hoefler G, Sattler W, Weinstock PH, Breslow JL, Zechner R. Source: The Journal of Clinical Investigation. 1995 August; 96(2): 976-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7635990

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Mutations in the gene for lipoprotein lipase. A cause for low HDL cholesterol levels in individuals heterozygous for familial hypercholesterolemia. Author(s): Pimstone SN, Gagne SE, Gagne C, Lupien PJ, Gaudet D, Williams RR, Kotze M, Reymer PW, Defesche JC, Kastelein JJ, et al. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1995 October; 15(10): 170412. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7583547

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Mutations in the lipoprotein lipase gene associated with ischemic heart disease in men. The Copenhagen city heart study. Author(s): Wittrup HH, Tybjaerg-Hansen A, Steffensen R, Deeb SS, Brunzell JD, Jensen G, Nordestgaard BG. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1999 June; 19(6): 1535-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10364086

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Myocardial dysfunction and male mortality in peroxisome proliferator-activated receptor alpha knockout mice overexpressing lipoprotein lipase in muscle. Author(s): Nohammer C, Brunner F, Wolkart G, Staber PB, Steyrer E, Gonzalez FJ, Zechner R, Hoefler G. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2003 February; 83(2): 259-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12594240

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Neonatal pancreatitis associated with familial lipoprotein lipase deficiency. Author(s): Siafakas CG, Brown MR, Miller TL. Source: Journal of Pediatric Gastroenterology and Nutrition. 1999 July; 29(1): 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10400113

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New mutations in the lipoprotein lipase gene in a young boy with chylomicronaemia syndrome and in his family. Author(s): Brites F, Henriksen F, Fernandez K, Brusgaard K, Castro G, Wikinski R. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 May; 92(5): 621-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12839295

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No association between the lipoprotein lipase S447X polymorphism and Alzheimer's disease. Author(s): Fidani L, Compton D, Hardy J, Petersen RC, Tangalos E, Mirtsou V, Goulas A, De Vrieze FW. Source: Neuroscience Letters. 2002 April 12; 322(3): 192-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897170

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No evidence of accelerated atherosclerosis in a 66-yr-old chylomicronemia patient homozygous for the nonsense mutation (Tyr61-->stop) in the lipoprotein lipase gene. Author(s): Ebara T, Okubo M, Horinishi A, Adachi M, Murase T, Hirano T. Source: Atherosclerosis. 2001 December; 159(2): 375-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11730817

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No linkage of the lipoprotein lipase locus to hypertension in Caucasians. Author(s): Hunt SC, Province MA, Atwood LD, Sholinsky P, Lalouel JM, Rao DC, Williams RR, Leppert MF. Source: Journal of Hypertension. 1999 January; 17(1): 39-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10100092

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Normal and pathological human testes express hormone-sensitive lipase and the lipid receptors CLA-1/SR-BI and CD36. Author(s): Arenas MI, Lobo MV, Caso E, Huerta L, Paniagua R, Martin-Hidalgo MA. Source: Human Pathology. 2004 January; 35(1): 34-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14745722

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Novel compound heterozygous mutations for lipoprotein lipase deficiency. A G-to-T transversion at the first position of exon 5 causing G154V missense mutation and a 5' splice site mutation of intron 8. Author(s): Ikeda Y, Takagi A, Nakata Y, Sera Y, Hyoudou S, Hamamoto K, Nishi Y, Yamamoto A. Source: Journal of Lipid Research. 2001 July; 42(7): 1072-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441134

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Novel site in lipoprotein lipase (LPL415;-438) essential for substrate interaction and dimer stability. Author(s): Keiper T, Schneider JG, Dugi KA. Source: Journal of Lipid Research. 2001 August; 42(8): 1180-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11483618

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Nutrient regulation of post-heparin lipoprotein lipase activity in obese subjects. Author(s): Ranganath LR, Beety JM, Wright J, Morgan LM. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 2001 January; 33(1): 57-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11280717

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Nutritional regulation of lipoprotein lipase. Author(s): Olivecrona T, Bergo M, Hultin M, Olivecrona G. Source: The Canadian Journal of Cardiology. 1995 October; 11 Suppl G: 73G-78G. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7585297

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One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Author(s): Finer N, James WP, Kopelman PG, Lean ME, Williams G. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2000 March; 24(3): 306-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10757623

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Optimal step length EM algorithm (OSLEM) for the estimation of haplotype frequency and its application in lipoprotein lipase genotyping. Author(s): Zhang P, Sheng H, Morabia A, Gilliam TC. Source: Bmc Bioinformatics [electronic Resource]. 2003 January 15; 4(1): 3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12529185

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Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study. Author(s): Hill JO, Hauptman J, Anderson JW, Fujioka K, O'Neil PM, Smith DK, Zavoral JH, Aronne LJ. Source: The American Journal of Clinical Nutrition. 1999 June; 69(6): 1108-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10357727

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Overexpressing human lipoprotein lipase in mouse skeletal muscle is associated with insulin resistance. Author(s): Ferreira LD, Pulawa LK, Jensen DR, Eckel RH. Source: Diabetes. 2001 May; 50(5): 1064-8. Erratum In: Diabetes 2001 June; 50(6): 1512. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11334409

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Overexpression of apoC-I in apoE-null mice: severe hypertriglyceridemia due to inhibition of hepatic lipase. Author(s): Conde-Knape K, Bensadoun A, Sobel JH, Cohn JS, Shachter NS. Source: Journal of Lipid Research. 2002 December; 43(12): 2136-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12454276

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Overexpression of human lipoprotein lipase protects diabetic transgenic mice from diabetic hypertriglyceridemia and hypercholesterolemia. Author(s): Shimada M, Ishibashi S, Gotoda T, Kawamura M, Yamamoto K, Inaba T, Harada K, Ohsuga J, Perrey S, Yazaki Y, et al. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1995 October; 15(10): 168894. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7583545

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Overexpression of lipoprotein lipase in transgenic rabbits inhibits diet-induced hypercholesterolemia and atherosclerosis. Author(s): Fan J, Unoki H, Kojima N, Sun H, Shimoyamada H, Deng H, Okazaki M, Shikama H, Yamada N, Watanabe T. Source: The Journal of Biological Chemistry. 2001 October 26; 276(43): 40071-9. Epub 2001 July 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11477088

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Overexpression of lipoprotein lipase in transgenic rabbits leads to increased small dense LDL in plasma and promotes atherosclerosis. Author(s): Ichikawa T, Kitajima S, Liang J, Koike T, Wang X, Sun H, Okazaki M, Morimoto M, Shikama H, Watanabe T, Yamada N, Fan J. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2004 June; 84(6): 715-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15122303

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Overexpression of lipoprotein lipase in transgenic Watanabe heritable hyperlipidemic rabbits improves hyperlipidemia and obesity. Author(s): Koike T, Liang J, Wang X, Ichikawa T, Shiomi M, Liu G, Sun H, Kitajima S, Morimoto M, Watanabe T, Yamada N, Fan J. Source: The Journal of Biological Chemistry. 2004 February 27; 279(9): 7521-9. Epub 2003 December 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14660566

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Oxidative modifications of LDL increase its binding to extracellular matrix from human aortic intima: influence of lesion development, lipoprotein lipase and calcium. Author(s): Wang X, Greilberger J, Ratschek M, Jurgens G. Source: The Journal of Pathology. 2001 September; 195(2): 244-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11592105

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Pancreatic bile salt-dependent lipase induces smooth muscle cells proliferation. Author(s): Auge N, Rebai O, Lepetit-Thevenin J, Bruneau N, Thiers JC, Mas E, Lombardo D, Negre-Salvayre A, Verine A. Source: Circulation. 2003 July 8; 108(1): 86-91. Epub 2003 June 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821548

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Pancreatic lipase-related protein 2 is the major colipase-dependent pancreatic lipase in suckling mice. Author(s): D'Agostino D, Lowe ME. Source: The Journal of Nutrition. 2004 January; 134(1): 132-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14704305

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Pancreatic triacylglycerol lipase in a hibernating mammal. I. Novel genomic organization. Author(s): Squire TL, Andrews MT. Source: Physiological Genomics. 2003 December 16; 16(1): 119-30. Epub 2003 October 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583598

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Pancreatic triacylglycerol lipase in a hibernating mammal. II. Cold-adapted function and differential expression. Author(s): Squire TL, Lowe ME, Bauer VW, Andrews MT. Source: Physiological Genomics. 2003 December 16; 16(1): 131-40. Epub 2003 October 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583599

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Pathogenic mutations of the lipoprotein lipase gene in Chinese patients with hypertriglyceridemic type 2 diabetes. Author(s): Yang T, Pang CP, Tsang MW, Lam CW, Poon PM, Chan LY, Wu XQ, Tomlinson B, Baum L. Source: Human Mutation. 2003 April; 21(4): 453. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12655575

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Plasma lipoprotein lipase, hepatic lipase activities, VLDL, LDL compositions at different times of hemodialysis. Author(s): Mekki K, Prost J, Bouchenak M, Remaoun M, Belleville J. Source: Atherosclerosis. 2003 August; 169(2): 269-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921978

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Postprandial triglyceride levels in familial combined hyperlipidemia. The role of apolipoprotein E and lipoprotein lipase polymorphisms. Author(s): Reiber I, Mezo I, Kalina A, Palos G, Romics L, Csaszar A. Source: The Journal of Nutritional Biochemistry. 2003 July; 14(7): 394-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915220

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Pre-heparin lipoprotein lipase mass. Author(s): Kobayashi J. Source: J Atheroscler Thromb. 2004; 11(1): 1-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15067192

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Preparation and characterization of reference materials for human pancreatic lipase: BCR 693 (from human pancreatic juice) and BCR 694 (recombinant). Author(s): Lessinger JM, Arzoglou P, Ramos P, Visvikis A, Parashou S, Calam D, Profilis C, Ferard G. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2003 February; 41(2): 169-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667003

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Pyrrolopyrazinedione-based inhibitors of human hormone-sensitive lipase. Author(s): Slee DH, Bhat AS, Nguyen TN, Kish M, Lundeen K, Newman MJ, McConnell SJ. Source: Journal of Medicinal Chemistry. 2003 March 27; 46(7): 1120-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12646020

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Quantification of lipoprotein lipase (LPL) by dissociation-enhanced lanthanide fluorescence immunoassay. Comparison of immunoreactivity of LPL mass and enzyme activity of LPL. Author(s): Wicher I, Sattler W, Ibovnik A, Kostner GM, Zechner R, Malle E. Source: Journal of Immunological Methods. 1996 June 10; 192(1-2): 1-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8699004

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Quantitative trait locus mapping of human blood pressure to a genetic region at or near the lipoprotein lipase gene locus on chromosome 8p22. Author(s): Wu DA, Bu X, Warden CH, Shen DD, Jeng CY, Sheu WH, Fuh MM, Katsuya T, Dzau VJ, Reaven GM, Lusis AJ, Rotter JI, Chen YD. Source: The Journal of Clinical Investigation. 1996 May 1; 97(9): 2111-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8621801

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Race differences in the response of postheparin plasma lipoprotein lipase and hepatic lipase activities to endurance exercise training in men: results from the HERITAGE Family Study. Author(s): Bergeron J, Couillard C, Despres JP, Gagnon J, Leon AS, Rao DC, Skinner JS, Wilmore JH, Bouchard C. Source: Atherosclerosis. 2001 December; 159(2): 399-406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11730820

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Rapid exchange of pancreatic lipase between triacylglycerol droplets. Author(s): Haiker H, Lengsfeld H, Hadvary P, Carriere F. Source: Biochimica Et Biophysica Acta. 2004 June 1; 1682(1-3): 72-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15158758

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Redesigning the active site of Geotrichum candidum lipase. Author(s): Schrag JD, Vernet T, Laramee L, Thomas DY, Recktenwald A, Okoniewska M, Ziomek E, Cygler M. Source: Protein Engineering. 1995 August; 8(8): 835-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8637854

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Regulation of lipolysis and lipoprotein lipase after weight loss in obese, postmenopausal women. Author(s): Berman DM, Nicklas BJ, Ryan AS, Rogus EM, Dennis KE, Goldberg AP. Source: Obesity Research. 2004 January; 12(1): 32-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742840

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Relation between pancreatic lipase activity and gastric emptying rate in children with cystic fibrosis. Author(s): Symonds EL, Omari TI, Webster JM, Davidson GP, Butler RN. Source: The Journal of Pediatrics. 2003 December; 143(6): 772-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657826

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Relationship between serum HDL-C levels and common genetic variants of the endothelial lipase gene in Japanese school-aged children. Author(s): Yamakawa-Kobayashi K, Yanagi H, Endo K, Arinami T, Hamaguchi H. Source: Human Genetics. 2003 September; 113(4): 311-5. Epub 2003 July 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12884003

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Relevance of hepatic lipase to the metabolism of triacylglycerol-rich lipoproteins. Author(s): Zambon A, Bertocco S, Vitturi N, Polentarutti V, Vianello D, Crepaldi G. Source: Biochemical Society Transactions. 2003 October; 31(Pt 5): 1070-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505482

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Remodeling of HDL by CETP in vivo and by CETP and hepatic lipase in vitro results in enhanced uptake of HDL CE by cells expressing scavenger receptor B-I. Author(s): Collet X, Tall AR, Serajuddin H, Guendouzi K, Royer L, Oliveira H, Barbaras R, Jiang XC, Francone OL. Source: Journal of Lipid Research. 1999 July; 40(7): 1185-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10393203

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Requirement for enzymatically active lipoprotein lipase in neuronal differentiation: a site-directed mutagenesis study. Author(s): Paradis E, Julien P, Ven Murthy MR. Source: Brain Research. Developmental Brain Research. 2004 March 22; 149(1): 29-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013626

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Retroviral-mediated gene transfer and expression of human lipoprotein lipase in somatic cells. Author(s): Lewis ME, Forsythe IJ, Marth JD, Brunzell JD, Hayden MR, Humphries RK. Source: Human Gene Therapy. 1995 July; 6(7): 853-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7578404

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Sequence analysis of amplified DNA fragments containing the region encoding the putative lipase substrate-binding domain and genotyping of Aeromonas hydrophila. Author(s): Watanabe N, Morita K, Furukawa T, Manzoku T, Endo E, Kanamori M. Source: Applied and Environmental Microbiology. 2004 January; 70(1): 145-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14711636

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Serum amylase and lipase alone are not cost-effective screening methods for pediatric pancreatic trauma. Author(s): Adamson WT, Hebra A, Thomas PB, Wagstaff P, Tagge EP, Othersen HB. Source: Journal of Pediatric Surgery. 2003 March; 38(3): 354-7; Discussion 354-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12632348

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Serum amylase and lipase in diabetic ketoacidosis. Author(s): Rizvi AA. Source: Diabetes Care. 2003 November; 26(11): 3193-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578269

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Serum levels of bile salt-stimulated lipase and breast feeding. Author(s): Shamir R, Nganga A, Berkowitz D, Diamond E, Lischinsky S, Lombardo D, Shehadeh N. Source: J Pediatr Endocrinol Metab. 2003 December; 16(9): 1289-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714753

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Severe acute necrotizing pancreatitis associated with lipoprotein lipase deficiency in childhood. Author(s): van Walraven LA, de Klerk JB, Postema RR. Source: Journal of Pediatric Surgery. 2003 September; 38(9): 1407-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523833

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Spontaneous rupture of mediastinal cystic teratoma with high levels of amylase, lipase, CA 19-9, CA 125 and CEA in cystic fluid: a case report. Author(s): Ege G, Akman H, Cakiroglu G, Kalayci G. Source: Acta Radiologica (Stockholm, Sweden : 1987). 2004 February; 45(1): 111-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15164790

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Stated versus actual lipase activity in pancreatic enzyme supplements: implications for clinical use. Author(s): O'Hare MM, McMaster C, Dodge JA. Source: Journal of Pediatric Gastroenterology and Nutrition. 1995 July; 21(1): 59-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8576816

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Structure of the pancreatic lipase-procolipase complex. Author(s): van Tilbeurgh H, Sarda L, Verger R, Cambillau C. Source: Nature. 1992 September 10; 359(6391): 159-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1522902

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Synthesis of monocaprin catalyzed by lipase. Author(s): Da Silva MA, Medeiros VC, Langone MA, Freire DM. Source: Applied Biochemistry and Biotechnology. 2003 Spring; 105 -108: 757-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12721413

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Systemic and forearm triglyceride metabolism: fate of lipoprotein lipase-generated glycerol and free fatty acids. Author(s): Miles JM, Park YS, Walewicz D, Russell-Lopez C, Windsor S, Isley WL, Coppack SW, Harris WS. Source: Diabetes. 2004 March; 53(3): 521-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14988233

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Testosterone administration to men increases hepatic lipase activity and decreases HDL and LDL size in 3 wk. Author(s): Herbst KL, Amory JK, Brunzell JD, Chansky HA, Bremner WJ. Source: American Journal of Physiology. Endocrinology and Metabolism. 2003 June; 284(6): E1112-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12736156

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The amino acid sequences of the carboxyl termini of human and mouse hepatic lipase influence cell surface association. Author(s): Brown RJ, Schultz JR, Ko KW, Hill JS, Ramsamy TA, White AL, Sparks DL, Yao Z. Source: Journal of Lipid Research. 2003 July; 44(7): 1306-14. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12700335

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The G-250A promoter polymorphism of the hepatic lipase gene predicts the conversion from impaired glucose tolerance to type 2 diabetes mellitus: the Finnish Diabetes Prevention Study. Author(s): Todorova B, Kubaszek A, Pihlajamaki J, Lindstrom J, Eriksson J, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Tuomilehto J, Uusitupa M, Laakso M; Finnish Diabetes Prevention Study. Source: The Journal of Clinical Endocrinology and Metabolism. 2004 May; 89(5): 2019-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15126514

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The interactive effects of hepatic lipase gene promoter polymorphisms with sex and obesity on high-density-lipoprotein cholesterol levels in Taiwanese-Chinese. Author(s): Ko YL, Hsu LA, Hsu KH, Ko YH, Lee YS. Source: Atherosclerosis. 2004 January; 172(1): 135-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14709367

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The lipoprotein lipase gene HindIII polymorphism is associated with lipid levels in early-onset type 2 diabetic patients. Author(s): Ma YQ, Thomas GN, Ng MC, Critchley JA, Chan JC, Tomlinson B. Source: Metabolism: Clinical and Experimental. 2003 March; 52(3): 338-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12647273

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The lipoprotein lipase Ser447Ter mutation and risk of stroke in the Chinese. Author(s): Zhao SP, Tong QG, Xiao ZJ, Cheng YC, Zhou HN, Nie S. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 April; 330(1-2): 161-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12636935

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The presence of a catalytically inactive form of hormone-sensitive lipase is associated with decreased lipolysis in abdominal subcutaneous adipose tissue of obese subjects. Author(s): Ray H, Beylot M, Arner P, Larrouy D, Langin D, Holm C, Large V. Source: Diabetes. 2003 June; 52(6): 1417-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12765952

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Triacylglycerols based on 2-(N-tert-butoxycarbonylamino)oleic acid are potent inhibitors of pancreatic lipase. Author(s): Magrioti V, Verger R, Constantinou-Kokotou V. Source: Journal of Medicinal Chemistry. 2004 January 15; 47(2): 288-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14711301

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Two cases with transient lipoprotein lipase (LPL) activity impairment: evidence for the possible involvement of an LPL inhibitor. Author(s): Nagasaka H, Kikuta H, Chiba H, Murano T, Harashima H, Ohtake A, Senzaki H, Sasaki N, Inoue I, Katayama S, Shirai K, Kobayashi K. Source: European Journal of Pediatrics. 2003 March; 162(3): 132-8. Epub 2003 January 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12655414

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Underestimation of acute pancreatitis: patients with only a small increase in amylase/lipase levels can also have or develop severe acute pancreatitis. Author(s): Lankisch PG, Burchard-Reckert S, Lehnick D. Source: Gut. 1999 April; 44(4): 542-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10075962

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Upregulation of macrophage lipoprotein lipase in patients with type 2 diabetes: role of peripheral factors. Author(s): Sartippour MR, Renier G. Source: Diabetes. 2000 April; 49(4): 597-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10871197

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Uptake of hypertriglyceridemic very low density lipoproteins and their remnants by HepG2 cells: the role of lipoprotein lipase, hepatic triglyceride lipase, and cell surface proteoglycans. Author(s): Huff MW, Miller DB, Wolfe BM, Connelly PW, Sawyez CG. Source: Journal of Lipid Research. 1997 July; 38(7): 1318-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9254059

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Use of naturally fluorescent triacylglycerols from Parinari glaberrimum to detect low lipase activities from Arabidopsis thaliana seedlings. Author(s): Beisson F, Ferte N, Nari J, Noat G, Arondel V, Verger R. Source: Journal of Lipid Research. 1999 December; 40(12): 2313-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10588957

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Use of pyrenemethyl laurate for fluorescence-based determination of lipase activity in intact living lymphoblastoid cells and for the diagnosis of acid lipase deficiency. Author(s): Negre-Salvayre A, Dagan A, Gatt S, Salvayre R. Source: The Biochemical Journal. 1993 September 15; 294 ( Pt 3): 885-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8397511

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Variants in the cholesterol ester transfer protein and lipoprotein lipase genes are predictors of plasma cholesterol response to dietary change. Author(s): Wallace AJ, Mann JI, Sutherland WH, Williams S, Chisholm A, Skeaff CM, Gudnason V, Talmud PJ, Humphries SE. Source: Atherosclerosis. 2000 October; 152(2): 327-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10998460

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Variation at the lipoprotein lipase and apolipoprotein AI-CIII gene loci are associated with fasting lipid and lipoprotein traits in a population sample from Iceland: interaction between genotype, gender, and smoking status. Author(s): Peacock RE, Temple A, Gudnason V, Rosseneu M, Humphries SE. Source: Genetic Epidemiology. 1997; 14(3): 265-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9181356

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Variation in the promoter of the human hormone sensitive lipase gene shows gender specific effects on insulin and lipid levels: results from the Ely study. Author(s): Talmud PJ, Palmen J, Luan J, Flavell D, Byrne CD, Waterworth DM, Wareham NJ. Source: Biochimica Et Biophysica Acta. 2001 November 29; 1537(3): 239-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11731226

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Variation near the region of the lipoprotein lipase gene and hypertension or blood pressure levels in Chinese. Author(s): Yang W, Huang J, Ge D, Yao C, Duan X, Gan W, Huang G, Zhao J, Hui R, Shen Y, Qiang B, Gu D. Source: Hypertens Res. 2003 June; 26(6): 459-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12862202

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Very-low-density lipoprotein of uremic patients is a poor substrate for bovine lipoprotein lipase in vitro. Author(s): Arnadottir M, Dallongeville J, Fruchart JC, Nilsson-Ehle P. Source: Metabolism: Clinical and Experimental. 1996 June; 45(6): 686-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8637441

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Virolytic action of lipoprotein lipase on hepatitis C virus in human sera. Author(s): Thomssen R, Bonk S. Source: Medical Microbiology and Immunology. 2002 May; 191(1): 17-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12137195

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Visceral adiposity, C-peptide levels, and low lipase activities predict HIVdyslipidemia. Author(s): Yarasheski KE, Tebas P, Claxton S, Marin D, Coleman T, Powderly WG, Semenkovich CF. Source: American Journal of Physiology. Endocrinology and Metabolism. 2003 October; 285(4): E899-905. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12837664

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Visceral obesity attenuates the effect of the hepatic lipase -514C>T polymorphism on plasma HDL-cholesterol levels in French-Canadian men. Author(s): St-Pierre J, Miller-Felix I, Paradis ME, Bergeron J, Lamarche B, Despres JP, Gaudet D, Vohl MC. Source: Molecular Genetics and Metabolism. 2003 January; 78(1): 31-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12559845

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Visceral obesity, hepatic lipase activity, and dyslipidemia in type 1 diabetes. Author(s): Sibley SD, Palmer JP, Hirsch IB, Brunzell JD. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 July; 88(7): 3379-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843191

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VLDL-bound lipoprotein lipase facilitates the cholesteryl ester transfer proteinmediated transfer of cholesteryl esters from HDL to VLDL. Author(s): Pruneta V, Pulcini T, Lalanne F, Marcais C, Berthezene F, Ponsin G, Moulin P. Source: Journal of Lipid Research. 1999 December; 40(12): 2333-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10588959

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What is the long-term efficacy and tolerability of orlistat, a gastrointestinal lipase inhibitor, for the treatment of obesity in primary care? Author(s): Leiser JP, Gunning K. Source: The Journal of Family Practice. 2000 June; 49(6): 572-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10923560

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

Finding Nutrition Studies on Lipase 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 “lipase” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on lipase: •

Characteristics and benefits of bile salt-stimulated lipase in human milk. Source: Nutrition-reviews (USA). (November 1984). volume 42(11) page 372-373.

Additional consumer oriented references include: •

Free fatty acids in plasma may exert feed-back control of lipoprotein lipase activity. Author(s): Department of Biochemistry, Vanderbilt University, Nashville, TN 37232. Source: Coniglio, J G Nutr-Revolume 1993 January; 51(1): 18-9 0029-6643

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Gastric lipase and digestion of human milk fat. Source: Schoeller, D.A. Nutr-Rev. New York, N.Y. : Springer-Verlag New York Inc. October 1990. volume 48 (10) page 385-387. 0029-6643

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Lipoprotein lipase genetic variation and gender-specific ischemic cerebrovascular disease risk. Author(s): Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA. Source: Ordovas, J M Nutr-Revolume 2000 October; 58(10): 315-8 0029-6643

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Rapid movement of lipoprotein lipase among substrate globules. Source: Nutr-Rev. Washington, D.C. : Nutrition Foundation. January 1985. volume 43 (1) page 29-30. 0029-6643

The following information is typical of that found when using the “Full IBIDS Database” to search for “lipase” (or a synonym): •

The effects of the long-term feeding of dietary lipase on the performance of laying hens. Author(s): Mendelova Zemedelska a Lesnicka Univ., Brno (Czech Republic). Ustav Chovu Hospodarskych Zvirat Source: Lichovnikova, M. Zeman, L. Klecker, D. Fialova, M. Czech-Journal-of-AnimalScience-UZPI (Czech Republic). (April 2002). volume 47(4) page 141-145.

Additional physician-oriented references include: •

A novel missense mutation in the gene for lipoprotein lipase resulting in a highly conservative amino acid substitution (Asp180 replaced by Glu) causes familial chylomicronemia (Type 1 hyperlipoproteinemia). Source: Haubenwallner, S. Horl, G. Shachter, N.S. Presta, E. Fried, S.K. Hofler, G. Kostner, G.M. Breslow, J.L. Zechner, R. Genomics. Orlando, Fla. : Academic Press, Inc. November 1993. volume 18 (2) page 392-396. 0888-7543

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Alternate conformations observed in catalytic serine of Bacillus subtilis lipase determined at 1.3 A resolution. Author(s): Structural Biology Group, Research Institute of Biological Resources, National Institute of Advanced Industrial Science and Technology (AIST), 2-17-2-1 Tsukisamu-Higashi, Toyohira, Sapporo 062-8517, Japan. Source: Kawasaki, K Kondo, H Suzuki, M Ohgiya, S Tsuda, S Acta-Crystallogr-D-BiolCrystallogr. 2002 July; 58(Pt 7): 1168-74 0907-4449

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Blocking the tunnel: engineering of Candida rugosa lipase mutants with short chain length specificity. Author(s): Institute of Technical Biology, University of Stuttgart, Allmandring 31, D70569 Stuttgart, Germany. Source: Schmitt, J Brocca, S Schmid, R D Pleiss, J Protein-Eng. 2002 July; 15(7): 595-601 0269-2139

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Changes in lipid content and lipase activity in the hen liver before and after the onset of laying. Source: Fujii, M. Fukunaga, T. Koga, K. New strategies for improving animal production for human welfare : proceedings / the Fifth World Conference on Animal Production, August 14-19, 1983. Tokyo, Japan : Japanese Society of Zootechnical Science, 1983. volume 2 page 285-286.

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Changes of gastric lipase activity after ethanol and indomethacin administration: influence of pretreatment with allopurinol, pentoxifylline and L-DOPA. Author(s): Department of Pharmacology, Faculty of Medicine, P.J. Safarik University, Kosice, Slovak Republic. Source: Sedlakova, A Kohut, A Sarissky, M Physiol-Res. 2001; 50(3): 299-307 0862-8408

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Combined effect of a lecithin and a bile salt on pancreatic lipase activity. Source: Lykidis, A. Avranas, A. Arzoglou, P. Comp-biochem-physiol-Part-B,-Biochemmol-biol. Tarrytown, NY : Elsevier Science Inc. January 1997. volume 116B (1) page 5155.

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Conversion of Bacillus thermocatenulatus lipase into an efficient phospholipase with increased activity towards long-chain fatty acyl substrates by directed evolution and rational design. Author(s): Institute for Technical Biochemistry, University of Stuttgart, Allmandring 31, D-70569 Stuttgart, Germany. Source: Kauffmann, I Schmidt Dannert, C Protein-Eng. 2001 November; 14(11): 919-28 0269-2139

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Effect of dichlorvos on the activity of lipoprotein lipase from adipose tissue, on plasma lipids and postheparin lipolytic plasma activity in rats. Source: Kozlowska, A. Sadurska, B. Szymczyk, T. Arch-Toxicol. Berlin, W. Ger. : Springer. 1988. volume 62 (2/3) page 227-229. 0340-5761

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Effect of dietary fatty acids on lipoprotein lipase gene expression in the liver and visceral adipose tissue of fed and starved red sea bream Pagrus major. Author(s): National Research Institute of Aquaculture, Nansei, Mie 516-0193, Japan. Source: Liang, X F Ogata, H Y Oku, H Comp-Biochem-Physiol-A-Mol-Integr-Physiol. 2002 August; 132(4): 913-9 1095-6433

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Effect of lipase activities of Propionibacterium granulosum and Propionibacterium acnes. Author(s): Department of Dermatology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan. Source: Higaki, S Nakamura, M Kitagawa, T Morohashi, M Yamagishi, T Drugs-ExpClin-Res. 2001; 27(5-6): 161-4 0378-6501

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Effects of hepatic lipase gene promoter nucleotide variations on serum HDL cholesterol concentration in the general Japanese population. Author(s): The Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan. [email protected]

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Source: Inazu, A Nishimura, Y Terada, Y Mabuchi, H J-Hum-Genet. 2001; 46(4): 172-7 1434-5161 •

Effects of hormones, fasting and diabetes on triglyceride lipase activities in rat heart and liver. Source: Stam, H. Schoonderwoerd, K. Breeman, W. Hulsmann, W.C. Horm-Metab-Res. Stuttgart, W. Ger. : Georg Thieme. June 1984. volume 16 (6) page 293-297. ill. 0018-5043

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Familial lipoprotein lipase deficiency and related disorders of chylomicron metabolism. Source: Nikkila, E.A. The Metabolic basis of inherited disease / [edited by] John B. Stanbury. [et al.]. 5th ed. New York : McGraw-Hill, 1983. page 622-642. ill. ISBN: 0070607265

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Hydrolysis of plant oils by means of lipase from Rhizopus nigricans. Source: Rucka, M. Turkiewicz, B. Zuk, J.S. Krystynowicz, A. Galas, E. Bioprocess-Eng. Berlin, W. Ger. : Springer-Verlag. November 1991. volume 7 (3) page 133-135. 0178-515X

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Influence of phytostanol phosphoryl ascorbate, FM-VP4, on pancreatic lipase activity and cholesterol accumulation within Caco-2 cells. Author(s): Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, B.C, Canada. Source: Ramaswamy, Manisha Yau, Edwin Wasan, Kishor M Boulanger, Kathy D Li, Ming Pritchard, P Haydn J-Pharm-Pharm-Sci. 2002 April; 5(1): 29-38 1482-1826

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Influence of processing temperature and seasonal change in diet on lipase activity and lipolysis during the mechanical separation of bovine milk. Source: Needs, E.C. Anderson, M. Payne, S.J. Ridout, E.A. J-Dairy-Res. Cambridge : Cambridge University Press. May 1985. volume 52 (2) page 255-266. ill. 0022-0299

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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

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Lipoprotein lipase and lysosomal acid lipase: two key enzymes of lipid metabolism. Source: Ameris, D. Greten, H. NATO-ASI-ser,-Ser-A,-Life-sci. New York : Plenum, 1984-. 1994. volume 266 page 121-128. 0258-1213

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Microwave-assisted rapid characterization of lipase selectivities. Author(s): Biotechnology Department, Center for Chemistry and Chemical Engineering, Lund University, Box 124, SE-22100, Lund, Sweden. Source: Bradoo, Sapna Rathi, Pooja Saxena, R K Gupta, Rani J-Biochem-BiophysMethods. 2002 April 18; 51(2): 115-20 0165-022X

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Modifying the chain-length selectivity of the lipase from Burkholderia cepacia KWI56 through in vitro combinatorial mutagenesis in the substrate-binding site. Author(s): Laboratory of Molecular Biotechnology, Graduate School of Biological and Agricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. Source: Yang, J Koga, Y Nakano, H Yamane, T Protein-Eng. 2002 February; 15(2): 147-52 0269-2139

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Modulation of adipocyte lipoprotein lipase expression as a strategy for preventing or treating visceral obesity. Author(s): Pantox Laboratories, 4622 Santa Fe St, San Diego, CA 92109, USA. Source: McCarty, M F Med-Hypotheses. 2001 August; 57(2): 192-200 0306-9877

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Retinal pigment epithelial acid lipase activity and lipoprotein receptors: effects of dietary omega-3 fatty acids. Author(s): Department of Ophthalmology, University of Michigan, Ann Arbor, USA. Source: Elner, V M Trans-Am-Ophthalmol-Soc. 2002; 100: 301-38 0065-9533

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Site differences in lipoprotein lipase activity. Source: Lithell, H. Recent-Adv-Obesity-Res. London : John Libbey & Company. 1987. page 77-81. 0306-7548

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Structural characterization of the N-linked oligosaccharides in bile salt-stimulated lipase originated from human breast milk. Source: Mechref, Y. Chen, P. Novotny, M.V. Glycobiology. Oxford : Oxford University Press. March 1999. volume 9 (3) page 227-234. 0959-6658

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Studies on the production of lipase from recombinant Staphylococcus carnosus. Source: Falk, M.P.F. Sanders, E.A. Deckwer, W.D. Appl-Microbiol-Biotech. Berlin, W. Ger. : Springer International. April 1991. volume 35 (1) page 10-13. 0175-7598

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Synthesis of extracellular lipase by a strain of Pseudomonas fluorescens isolated from raw camel milk. Source: Al Saleh, A.A. Zahran, A.S. Food-microbiol. London; Orlando : Academic Press, c1984-. April 1999. volume 16 (2) page 149-156. 0740-0020

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The crystal and molecular structure of the Rhizomucor miehei triacylglyceride lipase at 1.9 angstrom resolution. Source: Derewenda, Z.S. Derewenda, U. Dodson, G.G. J-Mol-Biol. London : Academic Press. October 5, 1992. volume 227 (3) page 818-839. 0022-2836

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The Drosophila melanogaster lipase homologs: a gene family with tissue and developmental specific expression. Source: Pistillo, D. Manzi, A. Tino, A. Boyl, P.P. Graziani, F. Malva, C. J-mol-biol. London; New York : Academic Press, 1959-. March 13, 1998. volume 276 (5) page 877885. 0022-2836

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The effects of feeding condition and dietary lipid level on lipoprotein lipase gene expression in liver and visceral adipose tissue of red sea bream Pagrus major. Author(s): Fish Nutrition Division, National Research Institute of Aquaculture, Nansei, Mie 516-0193, Japan. Source: Liang, Xu Fang Oku, Hiromi Ogata, Hiroshi Y Comp-Biochem-Physiol-A-MolIntegr-Physiol. 2002 February; 131(2): 335-42 1095-6433

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The role of nitrogen sources, vitamines and growth factors in lipase production by Penicillium lanosum westling. Source: Elwan, S.H. El Naggar, M.R. El Sheikh, H.H. J-Coll-Sci-King-Saud-Univ. Riyadh, Saudi Arabia : University Libraries, King Saud University. 1982. volume 13 (2) page 215226. 0735-9799

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The structure of truncated recombinant human bile salt-stimulated lipase reveals bile salt-independent conformational flexibility at the active-site loop and provides insights into heparin binding. Author(s): Institute of Molecular Biosciences, Massey University, Palmerston North, New Zealand.

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Source: Moore, S A Kingston, R L Loomes, K M Hernell, O Blackberg, L Baker, H M Baker, E N J-Mol-Biol. 2001 September 21; 312(3): 511-23 0022-2836 •

Yeast whole-cell biocatalyst constructed by intracellular overproduction of Rhizopus oryzae lipase is applicable to biodiesel fuel production. Author(s): Division of Molecular Science, Graduate School of Science and Technology, Kobe University, Japan. Source: Matsumoto, T Takahashi, S Kaieda, M Ueda, M Tanaka, A Fukuda, H Kondo, A Appl-Microbiol-Biotechnol. 2001 November; 57(4): 515-20 0175-7598

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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

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Healthnotes: http://www.healthnotes.com/

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

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

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

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

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

2,3,7,8-Tetrachlorodibenzo-p-dioxin mechanism of action to reduce lipoprotein lipase activity in the 3T3-L1 preadipocyte cell line. Author(s): Olsen H, Enan E, Matsumura F. Source: Journal of Biochemical and Molecular Toxicology. 1998; 12(1): 29-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9414485

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3-Methylethergalangin isolated from Alpinia officinarum inhibits pancreatic lipase. Author(s): Shin JE, Joo Han M, Kim DH. Source: Biological & Pharmaceutical Bulletin. 2003 June; 26(6): 854-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12808299

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A novel spectrophotometric assay for lipase activity utilizing cis-parinaric acid. Author(s): Rogel AM, Stone WL, Adebonojo FO.

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Source: Lipids. 1989 June; 24(6): 518-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2770430 •

A rapid colorimetric assay for the extracellular lipase of Pseudomonas fluorescens B52 using beta-naphthyl caprylate. Author(s): McKellar RC. Source: The Journal of Dairy Research. 1986 February; 53(1): 117-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3082952

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A vanadyl sulfate-bovine serum albumin complex stimulates the release of lipoprotein lipase activity from isolated rat fat pads through an increase in the cellular content of cAMP and myo-inositol 1,4,5-trisphosphate. Author(s): Motoyashiki T, Miyake M, Yoshida A, Morita T, Ueki H. Source: Biological & Pharmaceutical Bulletin. 1999 August; 22(8): 780-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10480313

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Acid lipase in rat intestinal mucosa: physiological parameters. Author(s): Rao RH, Mansbach CM 2nd. Source: Biochimica Et Biophysica Acta. 1990 April 17; 1043(3): 273-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2322572

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Adaptation of pancreatic lipase to the amount and nature of dietary lipids in the growing pig. Author(s): Simoes Nunes C. Source: Reproduction, Nutrition, Development. 1986; 26(6): 1273-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3823602

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Adipose hormone-sensitive lipase preferentially releases polyunsaturated fatty acids from triglycerides. Author(s): Gavino VC, Gavino GR. Source: Lipids. 1992 December; 27(12): 950-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1362594

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Ajoene prevents fat digestion by human gastric lipase in vitro. Author(s): Gargouri Y, Moreau H, Jain MK, de Haas GH, Verger R. Source: Biochimica Et Biophysica Acta. 1989 November 6; 1006(1): 137-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2804064

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Alkaline lipase in rat intestinal mucosa: physiological parameters. Author(s): Rao RH, Mansbach CM 2nd.

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Source: Archives of Biochemistry and Biophysics. 1993 August 1; 304(2): 483-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8346923 •

An accessory gene, lipB, required for the production of active Pseudomonas glumae lipase. Author(s): Frenken LG, Bos JW, Visser C, Muller W, Tommassen J, Verrips CT. Source: Molecular Microbiology. 1993 August; 9(3): 579-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8412704

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Anti-lipase activity of Kampo formulations, coptidis rhizoma and its alkaloids against Propionibacterium acnes. Author(s): Higaki S, Nakamura M, Morohashi M, Hasegawa Y, Yamagishi T. Source: The Journal of Dermatology. 1996 May; 23(5): 310-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8675819

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Anti-lipase activity of Unsei-in against Propionibacterium avidum in the human axilla. Author(s): Higaki S, Morohashi M, Yamagishi T. Source: International Journal of Antimicrobial Agents. 2003 June; 21(6): 597-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791480

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Anti-obesity effect of Dioscorea nipponica Makino with lipase-inhibitory activity in rodents. Author(s): Kwon CS, Sohn HY, Kim SH, Kim JH, Son KH, Lee JS, Lim JK, Kim JS. Source: Bioscience, Biotechnology, and Biochemistry. 2003 July; 67(7): 1451-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12913286

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Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame Herba, on rats fed a high-fat diet. Author(s): Yamamoto M, Shimura S, Itoh Y, Ohsaka T, Egawa M, Inoue S. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2000 June; 24(6): 758-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10878683

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ATP-induced potentiation of G-protein-dependent phospholipase D activity in a cellfree system from U937 promonocytic leukocytes. Author(s): Kusner DJ, Schomisch SJ, Dubyak GR. Source: The Journal of Biological Chemistry. 1993 September 25; 268(27): 19973-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8376359

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Basic fibroblast growth factor-stimulated arachidonic acid release in rat pancreatic acini: sequential action of tyrosine kinase, phospholipase C, protein kinase C and

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diacylglycerol lipase. Author(s): Hou W, Arita Y, Morisset J. Source: Cellular Signalling. 1996 November; 8(7): 487-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9023013 •

Beneficial effects of fish-oil supplements on lipids, lipoproteins, and lipoprotein lipase in patients with glycogen storage disease type I. Author(s): Levy E, Thibault L, Turgeon J, Roy CC, Gurbindo C, Lepage G, Godard M, Rivard GE, Seidman E. Source: The American Journal of Clinical Nutrition. 1993 June; 57(6): 922-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8503363

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Bile salt-dependent lipase biosynthesis in rat pancreatic AR 4-2 J cells. Essential requirement of N-linked oligosaccharide for secretion and expression of a fully active enzyme. Author(s): Abouakil N, Mas E, Bruneau N, Benajiba A, Lombardo D. Source: The Journal of Biological Chemistry. 1993 December 5; 268(34): 25755-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8245011

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Biocatalytic potential of Fusarium globulosum lipase in selective acetylation/deacetylation reactions and in ester synthesis. Author(s): Gulati R, Bhattacharya A, Prasad AK, Gupta R, Parmar VS, Saxena RK. Source: Journal of Applied Microbiology. 2001 April; 90(4): 609-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11309073

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Biochemical analysis of a native and proteolytic fragment of a high-molecular-weight thermostable lipase from a mesophilic Bacillus sp. Author(s): Dosanjh NS, Kaur J. Source: Protein Expression and Purification. 2002 February; 24(1): 71-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11812225

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Biotechnology for the production of nutraceuticals enriched in conjugated linoleic acid: I. Uniresponse kinetics of the hydrolysis of corn oil by a pseudomonas sp. lipase immobilized in a hollow fiber reactor Author(s): Sehanputri PS, Hill CG Jr. Source: Biotechnology and Bioengineering. 1999 September 5; 64(5): 568-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10404237

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Biotechnology for the production of nutraceuticals enriched in conjugated linoleic acid: II. Multiresponse kinetics of the hydrolysis of corn oil by a Pseudomonas sp. lipase immobilized in a hollow-fiber reactor. Author(s): Sehanputri PS, Hill CG Jr.

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Source: Biotechnology and Bioengineering. 2000 August 20; 69(4): 450-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10862683 •

Calcium ion-dependent reactivation of a Pseudomonas lipase by its specific modulating protein, LipB. Author(s): Shibata H, Kato H, Oda J. Source: Journal of Biochemistry. 1998 January; 123(1): 136-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9504420

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Changes in lipolysis and hormone-sensitive lipase expression caused by procyanidins in 3T3-L1 adipocytes. Author(s): Ardevol A, Blade C, Salvado MJ, Arola L. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2000 March; 24(3): 319-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10757625

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Characterisation of a phospholipase C produced by Pseudomonas fluorescens. Author(s): Ivanov A, Titball RW, Kostadinova S. Source: New Microbiol. 1996 April; 19(2): 113-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8722307

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Characterization and physicochemical properties of a lipase from Pseudomonas mendocina 3121-1. Author(s): Surinenaite B, Bendikiene V, Juodka B, Bachmatova I, Marcinkevichiene L. Source: Biotechnology and Applied Biochemistry. 2002 August; 36(Pt 1): 47-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149122

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Characterization of a highly thermostable extracellular lipase from Lactobacillus plantarum. Author(s): Lopes Mde F, Leitao AL, Regalla M, Marques JJ, Carrondo MJ, Crespo MT. Source: International Journal of Food Microbiology. 2002 June 5; 76(1-2): 107-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12038566

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Characterization of a novel mutation causing hepatic lipase deficiency among French Canadians. Author(s): Ruel IL, Couture P, Gagne C, Deshaies Y, Simard J, Hegele RA, Lamarche B. Source: Journal of Lipid Research. 2003 August; 44(8): 1508-14. Epub 2003 June 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12777476

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Characterization of a pyoverdine-deficient mutant of Pseudomonas fluorescens impaired in the secretion of extracellular lipase. Author(s): Fernandez L, San Jose C, Cholette H, McKellar RC.

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Source: Archives of Microbiology. 1988; 150(6): 523-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3144957 •

Characterization of LDL particle size among carriers of a defective or a null mutation in the lipoprotein lipase gene: the Quebec LIPD Study. Author(s): Ruel IL, Gaudet D, Perron P, Bergeron J, Julien P, Lamarche B. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 July 1; 22(7): 1181-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117735

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Characterization of lipoprotein lipase activity, secretion, and degradation at different sites of post-translational processing in primary cultures of rat adipocytes. Author(s): Simsolo RB, Ong JM, Kern PA. Source: Journal of Lipid Research. 1992 December; 33(12): 1777-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1479287

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Comparative effects of dietary fish oil and carbohydrate on plasma lipids and hepatic activities of phosphatidate phosphohydrolase, diacylglycerol acyltransferase and neutral lipase activities in the rat. Author(s): Marsh JB, Topping DL, Nestel PJ. Source: Biochimica Et Biophysica Acta. 1987 November 21; 922(2): 239-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2823908

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Comparison of a high lipase pancreatic enzyme extract with a regular pancreatin preparation in adult cystic fibrosis patients. Author(s): Gan KH, Heijerman HG, Geus WP, Bakker W, Lamers CB. Source: Alimentary Pharmacology & Therapeutics. 1994 December; 8(6): 603-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7696449

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Comparison of the lipolysis of chylomicron remnants derived from corn oil or olive oil by hepatic lipase in vitro. Author(s): Botham KM, Mayes PA, Avella M, Cantafora A, Bravo E. Source: Biochemical Society Transactions. 1995 May; 23(2): 284S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7672310

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Corn oil, palm oil and butterfat fractions affect postprandial lipemia and lipoprotein lipase in meal-fed rats. Author(s): Lai HC, Ney DM. Source: The Journal of Nutrition. 1995 June; 125(6): 1536-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7782908

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Daio-Orengedokuto inhibits HMG-CoA reductase and pancreatic lipase. Author(s): Kim YS, Jung EA, Shin JE, Chang JC, Yang HK, Kim NJ, Cho KH, Bae HS, Moon SK, Kim DH.

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Degradation of arachidonyl phospholipids catalyzed by two phospholipases A2 and phospholipase C in a lipopolysaccharide-treated macrophage cell line RAW264.7. Author(s): Tanaka Y, Amano F, Kishi H, Nishijima M, Akamatsu Y. Source: Archives of Biochemistry and Biophysics. 1989 July; 272(1): 210-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2500062

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Differences in glucose-dependent insulinotrophic polypeptide hormone and hepatic lipase in subjects of southern and northern Europe: implications for postprandial lipemia. Author(s): Jackson KG, Zampelas A, Knapper JM, Roche HM, Gibney MJ, Kafatos A, Gould BJ, Wright JW, Williams CM. Source: The American Journal of Clinical Nutrition. 2000 January; 71(1): 13-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10617941

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Digestion of triacylglycerols containing long-chain polyenoic fatty acids in vitro by colipase-dependent pancreatic lipase and human milk bile salt-stimulated lipase. Author(s): Chen Q, Blackberg L, Nilsson A, Sternby B, Hernell O. Source: Biochimica Et Biophysica Acta. 1994 January 3; 1210(2): 239-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8280776

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Does the bile salt-stimulated lipase of human milk have a role in the use of the milk long-chain polyunsaturated fatty acids? Author(s): Hernell O, Blackberg L, Chen Q, Sternby B, Nilsson A. Source: Journal of Pediatric Gastroenterology and Nutrition. 1993 May; 16(4): 426-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8315552

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Does vitellogenin inhibit lipoprotein lipase in the laying hen? Author(s): Griffin H. Source: Comparative Biochemistry and Physiology. B, Comparative Biochemistry. 1986; 85(2): 469-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3096631

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Dyslipidaemia in a boy with recurrent abdominal pain, hypersalivation and decreased lipoprotein lipase activity. Author(s): Matern D, Seydewitz H, Niederhoff H, Wiebusch H, Brandis M. Source: European Journal of Pediatrics. 1996 August; 155(8): 660-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8839720

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Effect of 6 dietary fatty acids on the postprandial lipid profile, plasma fatty acids, lipoprotein lipase, and cholesterol ester transfer activities in healthy young men. Author(s): Tholstrup T, Sandstrom B, Bysted A, Holmer G. Source: The American Journal of Clinical Nutrition. 2001 February; 73(2): 198-208. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11157314

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Effect of Acanthopanax senticosus on lipoprotein lipase in 3T3-L1 adipocytes. Author(s): Yang JY, Lee KS, Kim MK, Moon SK, Kang MK, Park BH, Kim JS, Park JW. Source: Phytotherapy Research : Ptr. 2004 February; 18(2): 160-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15022170

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Effect of bacterial or porcine lipase with low- or high-fat diets on nutrient absorption in pancreatic-insufficient dogs. Author(s): Suzuki A, Mizumoto A, Rerknimitr R, Sarr MG, DiMango EP. Source: Gastroenterology. 1999 February; 116(2): 431-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9922325

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Effect of capsaicin on skeletal muscle lipoprotein lipase in rats fed high fat diet. Author(s): Srinivasan MR, Satyanarayana MN. Source: Indian J Exp Biol. 1989 October; 27(10): 910-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2635151

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Effect of cod liver oil supplementation on plasma lipids, lipoproteins, lipase activity and platelet aggregation in normotensive and hypertensive volunteers. Author(s): Jethmalani SM, Viswanathan G, Noronha JM. Source: Indian J Exp Biol. 1989 December; 27(12): 1103-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2633973

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Effect of dietary fatty acids on lipoprotein lipase gene expression in the liver and visceral adipose tissue of fed and starved red sea bream Pagrus major. Author(s): Liang XF, Ogata HY, Oku H. Source: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology. 2002 August; 132(4): 913-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12095871

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Effect of dietary fiber on pancreatic lipase activity in vitro. Author(s): Hansen WE. Source: Pancreas. 1987; 2(2): 195-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2819858

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Effect of dietary saturated fatty acids on intracellular free fatty acids and kinetic properties of hormone-sensitive lipase of rat adipocytes. Author(s): Awad AB, Chattopadhyay JP.

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Effect of hepatoprotective ayurvedic drugs on lipases following CCl4 induced hepatic injury in rats. Author(s): Patil S, Kanase A, Varute AT. Source: Indian J Exp Biol. 1989 November; 27(11): 955-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2620934

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Effect of lipase activities of Propionibacterium granulosum and Propionibacterium acnes. Author(s): Higaki S, Nakamura M, Kitagawa T, Morohashi M, Yamagishi T. Source: Drugs Exp Clin Res. 2001; 27(5-6): 161-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11951573

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Effect of lipase inhibition on gastric emptying of, and the glycemic and incretin responses to, an oil/aqueous drink in type 2 diabetes mellitus. Author(s): Pilichiewicz A, O'Donovan D, Feinle C, Lei Y, Wishart JM, Bryant L, Meyer JH, Horowitz M, Jones KL. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 August; 88(8): 3829-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915676

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Effect of obesity on HDL and LDL particle sizes in carriers of the null P207L or defective D9N mutation in the lipoprotein lipase gene: the Quebec LipD Study. Author(s): Ruel IL, Gaudet D, Perron P, Bergeron J, Julien P, Lamarche B; Quebec LipD Study. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2003 May; 27(5): 631-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704407

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Effect of phosphatidylcholine and free fatty acids on the activity of pancreatic lipasecolipase. Author(s): Larsson A, Erlanson-Albertsson C. Source: Biochimica Et Biophysica Acta. 1986 May 21; 876(3): 543-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3707983

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Effect of taxol on the heparin-induced secretion of lipoprotein lipase from cardiac myocytes. Author(s): Severson DL, Carroll R. Source: Molecular and Cellular Biochemistry. 1989 June 27-July 24; 88(1-2): 17-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2571074

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Effect of temperature, moisture, and carbon supplementation on lipase production by solid-state fermentation of soy cake by Penicillium simplicissimum. Author(s): Di Luccio M, Capra F, Ribeiro NP, Vargas GD, Freire DM, de Oliveira D. Source: Applied Biochemistry and Biotechnology. 2004 Spring; 113-116: 173-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15054204

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Effects of arachidonic and docosahexaenoic acids on secretion and degradation of bile salt-dependent lipase in AR4-2J cells. Author(s): Le Petit-Thevenin J, Bruneau N, Nganga A, Lombardo D, Verine A. Source: Journal of Lipid Research. 2001 August; 42(8): 1220-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11483623

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Effects of cholestyramine feeding on tissue lipase activities and plasma fatty acids in the pregnant rat. Author(s): Haave NC, Innis SM. Source: J Dev Physiol. 1989 July; 12(1): 11-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2614036

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Effects of dietary saturated and polyunsaturated fat on lipoprotein lipase and hepatic triglyceride lipase activity. Author(s): Coiffier E, Paris R, Lecerf J. Source: Comparative Biochemistry and Physiology. B, Comparative Biochemistry. 1987; 88(1): 187-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3677597

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Effects of diets supplemented with lard fat or mackerel oil on plasma lipoprotein lipid concentrations and lipoprotein lipase activities in domestic swine. Author(s): Groot PH, Scheek LM, Dubelaar ML, Verdouw PD, Hartog JM, Lamers JM. Source: Atherosclerosis. 1989 May; 77(1): 1-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2719757

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Effects of human pancreatic lipase-colipase and carboxyl ester lipase on eicosapentaenoic and arachidonic acid ester bonds of triacylglycerols rich in fish oil fatty acids. Author(s): Chen Q, Sternby B, Akesson B, Nilsson A. Source: Biochimica Et Biophysica Acta. 1990 May 1; 1044(1): 111-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2340300

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Effects of manufactured soluble dietary fiber from Quercus mongolica on hepatic HMG-CoA reductase and lipoprotein lipase activities in epididymal adipose tissue of rats fed high cholesterol diets. Author(s): Chai YM, Lim BK, Lee JY, Kim MN, Park MR, Rhee SJ.

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Source: Journal of Medicinal Food. 2003 Winter; 6(4): 329-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977441 •

Effects of omega-3 fish oils on plasma lipids, lipoprotein composition, and postheparin lipoprotein lipase in women with IDDM. Author(s): Bagdade JD, Buchanan WE, Levy RA, Subbaiah PV, Ritter MC. Source: Diabetes. 1990 April; 39(4): 426-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2318345

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Effects of tetrahydrolipstatin, a lipase inhibitor, on absorption of fat from the intestine of the rat. Author(s): Fernandez E, Borgstrom B. Source: Biochimica Et Biophysica Acta. 1989 February 20; 1001(3): 249-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2917150

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Enhancement of the vanadate-stimulated release of lipoprotein lipase activity by astilbin from the leaves of Engelhardtia chrysolepis. Author(s): Motoyashiki T, Miyake M, Morita T, Mizutani K, Masuda H, Ueki H. Source: Biological & Pharmaceutical Bulletin. 1998 May; 21(5): 517-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9635510

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Enzymatic hydrolysis of carotenoid fatty acid esters of red pepper (Capsicum annuum L.) by a lipase from Candida rugosa. Author(s): Breithaupt DE. Source: Z Naturforsch [c]. 2000 November-December; 55(11-12): 971-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11204204

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Enzymatic synthesis of a capsinoid by the acylation of vanillyl alcohol with fatty acid derivatives catalyzed by lipases. Author(s): Kobata K, Kawaguchi M, Watanabe T. Source: Bioscience, Biotechnology, and Biochemistry. 2002 February; 66(2): 319-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11999404

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Esterification of polyunsaturated fatty acids by various forms of immobilized lipase from Rhizomucor miehei. Author(s): Kosugi Y, Roy PK, Chang Q, Shu-Gui C, Fukatsu M, Kanazawa K, Nakanishi H. Source: Lipids. 2000 April; 35(4): 461-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10858032

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Evidence of GTP-binding protein regulation of phospholipase A2 activity in isolated human platelet membranes. Author(s): Silk ST, Clejan S, Witkom K.

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Evidence that hepatic lipase deficiency in humans is not associated with proatherogenic changes in HDL composition and metabolism. Author(s): Ruel IL, Couture P, Cohn JS, Bensadoun A, Marcil M, Lamarche B. Source: Journal of Lipid Research. 2004 August; 45(8): 1528-37. Epub 2004 June 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15175359

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Extracellular protease and phospholipase C are controlled by the global regulatory gene gacA in the biocontrol strain Pseudomonas fluorescens CHA0. Author(s): Sacherer P, Defago G, Haas D. Source: Fems Microbiology Letters. 1994 February 15; 116(2): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8150259

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Fatty acid steryl, stanyl, and steroid esters by esterification and transesterification in vacuo using Candida rugosa lipase as catalyst. Author(s): Weber N, Weitkamp P, Mukherjee KD. Source: Journal of Agricultural and Food Chemistry. 2001 January; 49(1): 67-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11170561

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Further characterization of the acidic GPI-hydrolyzing phospholipase present in human sera. Author(s): Stambuk BU, Cardoso-de-Almeida ML. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 1994 February; 27(2): 383-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8081253

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Glycosylation, activity and secretion of lipoprotein lipase in cultured brown adipocytes of newborn mice. Effect of tunicamycin, monensin, 1deoxymannojirimycin and swainsonine. Author(s): Masuno H, Schultz CJ, Park JW, Blanchette-Mackie EJ, Mateo C, Scow RO. Source: The Biochemical Journal. 1991 August 1; 277 ( Pt 3): 801-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1831351

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Hydrolysis of long-chain, n-3 fatty acid enriched chylomicrons by cardiac lipoprotein lipase. Author(s): Levy R, Herzberg GR. Source: Canadian Journal of Physiology and Pharmacology. 1999 October; 77(10): 813-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10588486

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Hydrolysis of menhaden oil by a Candida cylindracea lipase immobilized in a hollow-fiber reactor. Author(s): Rice KE, Watkins J, Hill CG Jr. Source: Biotechnology and Bioengineering. 1999 April 5; 63(1): 33-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10099579

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Hydrolysis of steryl esters by a lipase (Lip 3) from Candida rugosa. Author(s): Tenkanen M, Kontkanen H, Isoniemi R, Spetz P, Holmbom B. Source: Applied Microbiology and Biotechnology. 2002 October; 60(1-2): 120-7. Epub 2002 August 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12382052

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Hypotriglyceridemic action of omega-3 fatty acids in healthy subjects does not occur by enhanced lipoprotein lipase and hepatic lipase activities. Author(s): Desager JP, Dricot J, Harvengt C. Source: Res Commun Chem Pathol Pharmacol. 1989 August; 65(2): 269-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2587847

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Identification of extracellular phospholipase B, lysophospholipase, and acyltransferase produced by Cryptococcus neoformans. Author(s): Chen SC, Wright LC, Santangelo RT, Muller M, Moran VR, Kuchel PW, Sorrell TC. Source: Infection and Immunity. 1997 February; 65(2): 405-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9009289

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Identification of the ricin lipase site and implication in cytotoxicity. Author(s): Morlon-Guyot J, Helmy M, Lombard-Frasca S, Pignol D, Pieroni G, Beaumelle B. Source: The Journal of Biological Chemistry. 2003 May 9; 278(19): 17006-11. Epub 2003 February 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611897

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Immobilization of lipases on polyethylene and application to perilla oil hydrolysis for production of alpha-linolenic acid. Author(s): Watanabe T, Suzuki Y, Sagesaka Y, Kohashi M. Source: J Nutr Sci Vitaminol (Tokyo). 1995 June; 41(3): 307-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7472675

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Influence of n-3 fatty acid supplementation on the endogenous activities of plasma lipases. Author(s): Harris WS, Lu G, Rambjor GS, Walen AI, Ontko JA, Cheng Q, Windsor SL.

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Influence of phytostanol phosphoryl ascorbate, FM-VP4, on pancreatic lipase activity and cholesterol accumulation within Caco-2 cells. Author(s): Ramaswamy M, Yau E, Wasan KM, Boulanger KD, Li M, Pritchard PH. Source: Journal of Pharmacy & Pharmaceutical Sciences [electronic Resource] : a Publication of the Canadian Society for Pharmaceutical Sciences, Societe Canadienne Des Sciences Pharmaceutiques. 2002 January-April; 5(1): 29-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12042117

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Inhibition of Candida rugosa lipase by berberine and structurally related alkaloids, evaluated by high-performance liquid chromatography. Author(s): Grippa E, Valla R, Battinelli L, Mazzanti G, Saso L, Silvestrini B. Source: Bioscience, Biotechnology, and Biochemistry. 1999 September; 63(9): 1557-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10540743

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Inhibition of human gastric lipase by intraduodenal fat involves glucagon-like peptide-1 and cholecystokinin. Author(s): Wojdemann M, Riber C, Bisgaard T, Sternby B, Larsen S, Rehfeld JF, Holst JJ, Olsen O. Source: Regulatory Peptides. 1999 April 30; 80(3): 101-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10425652

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Inhibition of lipase activities by citrus pectin. Author(s): Tsujita T, Sumiyosh M, Han LK, Fujiwara T, Tsujita J, Okuda H. Source: J Nutr Sci Vitaminol (Tokyo). 2003 October; 49(5): 340-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14703309

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Inhibitory effect of spice oils on lipase and mycotoxin production. Author(s): Hasan HA, Mahmoud AL. Source: Zentralbl Mikrobiol. 1993 December; 148(8): 543-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8303954

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Inhibitory effects of grape seed extract on lipases. Author(s): Moreno DA, Ilic N, Poulev A, Brasaemle DL, Fried SK, Raskin I. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2003 October; 19(10): 876-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14559324

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Involvement of phospholipase A2 and arachidonic acid in the depolarization-evoked accumulation of Ca2+ in hippocampal mossy fiber nerve endings. Author(s): Damron DS, Dorman RV.

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Source: Neurochemical Research. 1993 December; 18(12): 1231-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8272188 •

Kinetic assay of human gastric lipase on short- and long-chain triacylglycerol emulsions. Author(s): Gargouri Y, Pieroni G, Riviere C, Sauniere JF, Lowe PA, Sarda L, Verger R. Source: Gastroenterology. 1986 October; 91(4): 919-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3743968

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Lipase activity and gene cloning of Acinetobacter calcoaceticus LP009. Author(s): Dharmsthiti S, Pratuangdejkul J, Theeragool GT, Luchai S. Source: J Gen Appl Microbiol. 1998 April; 44(2): 139-145. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12501281

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Lipase and protease extraction from activated sludge. Author(s): Gessesse A, Dueholm T, Petersen SB, Nielsen PH. Source: Water Research. 2003 September; 37(15): 3652-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12867331

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Lipase from Chromobacterium viscosum: biochemical characterization indicating homology to the lipase from Pseudomonas glumae. Author(s): Taipa MA, Liebeton K, Costa JV, Cabral JM, Jaeger KE. Source: Biochimica Et Biophysica Acta. 1995 June 6; 1256(3): 396-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7786905

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Lipase mediated upgradation of dietary fats and oils. Author(s): Gupta R, Rathi P, Bradoo S. Source: Critical Reviews in Food Science and Nutrition. 2003; 43(6): 635-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14669881

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Lipase production by Aspergillus niger under various growth conditions using solid state fermentation. Author(s): Olama ZA, el-Sabaeny AH. Source: Microbiologia. 1993 December; 9(2): 134-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8172691

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Lipase-catalyzed chemo- and enantioselective acetylation of 2-alkyl/aryl-3hydroxypropiophenones. Author(s): Kumar R, Azim A, Kumar V, Sharma SK, Prasad AK, Howarth OW, Olsen CE, Jain SC, Parmar VS.

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Lipase-catalyzed ethanolysis of fish oils: multi-response kinetics. Author(s): Torres CF, Moeljadi M, Hill CG Jr. Source: Biotechnology and Bioengineering. 2003 August 5; 83(3): 274-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12783483

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Lipase-catalyzed interesterification of soybean oil with an omega-3 polyunsaturated fatty acid concentrate prepared from sardine oil. Author(s): Akimoto M, Izawa M, Hoshino K, Abe K, Takahashi H. Source: Applied Biochemistry and Biotechnology. 2003 February; 104(2): 105-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603099

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Lipase-mediated acidolysis of butteroil with free conjugated linoleic acid in a packed bed reactor. Author(s): Sehanputri PS, Hill CG Jr. Source: Biotechnology and Bioengineering. 2003 September 5; 83(5): 608-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827703

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Lipolysis of menhaden oil triacylglycerols and the corresponding fatty acid alkyl esters by pancreatic lipase in vitro: a reexamination. Author(s): Yang LY, Kuksis A, Myher JJ. Source: Journal of Lipid Research. 1990 January; 31(1): 137-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2313198

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Lipolysis of polyenoic fatty acid esters of human chylomicrons by lipoprotein lipase. Author(s): Ekstrom B, Nilsson A, Akesson B. Source: European Journal of Clinical Investigation. 1989 June; 19(3): 259-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2553422

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Lipophorin lipase from the yolk of Manduca sexta eggs: identification and partial characterization. Author(s): Van Antwerpen R, Law JH. Source: Archives of Insect Biochemistry and Physiology. 1992; 20(1): 1-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1623220

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Lipoprotein lipase activation by red ginseng saponins in hyperlipidemia model animals. Author(s): Inoue M, Wu CZ, Dou DQ, Chen YJ, Ogihara Y.

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Lipoprotein lipase activity in skeletal muscles of the rat: effects of denervation and tenotomy. Author(s): Smol E, Zernicka E, Czarnowski D, Langfort J. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2001 March; 90(3): 954-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11181606

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Lipoprotein lipase in rats fed fish oil: apparent relationship to plasma insulin levels. Author(s): Baltzell JK, Wooten JT, Otto DA. Source: Lipids. 1991 April; 26(4): 289-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1865765

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Lipoprotein lipase synthesis and secretion: effects of concentration and type of fatty acids in adipocyte cell culture. Author(s): Montalto MB, Bensadoun A. Source: Journal of Lipid Research. 1993 March; 34(3): 397-407. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8468524

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Lipoprotein lipases, lipoprotein density gradient profile and LDL receptor activity in miniature pigs fed fish oil and corn oil. Author(s): Huff MW, Telford DE, Edmonds BW, McDonald CG, Evans AJ. Source: Biochimica Et Biophysica Acta. 1993 December 2; 1210(1): 113-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8257713

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Lipoprotein lipases, lipoproteins and tissue lipids in rats fed fish oil or coconut oil. Author(s): Haug A, Hostmark AT. Source: The Journal of Nutrition. 1987 June; 117(6): 1011-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3598712

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Low-temperature lipase from psychrotrophic Pseudomonas sp. strain KB700A. Author(s): Rashid N, Shimada Y, Ezaki S, Atomi H, Imanaka T. Source: Applied and Environmental Microbiology. 2001 September; 67(9): 4064-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11526006

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Lysophospholipase A activity of Pseudomonas aeruginosa type III secretory toxin ExoU. Author(s): Tamura M, Ajayi T, Allmond LR, Moriyama K, Wiener-Kronish JP, Sawa T.

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Mechanism of angiotensin II-induced arachidonic acid metabolite release in aortic smooth muscle cells: involvement of phospholipase D. Author(s): Shinoda J, Kozawa O, Suzuki A, Watanabe-Tomita Y, Oiso Y, Uematsu T. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1997 February; 136(2): 207-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9116917

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Mechanism of cAMP-induced Ca2+ influx in Dictyostelium: role of phospholipase A2. Author(s): Schaloske R, Malchow D. Source: The Biochemical Journal. 1997 October 1; 327 ( Pt 1): 233-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9355757

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Method for the measurement of lipase activity in milk. Author(s): Humbert G, Guingamp MF, Linden G. Source: The Journal of Dairy Research. 1997 August; 64(3): 465-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9275261

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Milk lipid digestion in the neonatal dog: the combined actions of gastric and bile salt stimulated lipases. Author(s): Iverson SJ, Kirk CL, Hamosh M, Newsome J. Source: Biochimica Et Biophysica Acta. 1991 April 24; 1083(1): 109-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2031934

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Modulation of adipocyte lipoprotein lipase expression as a strategy for preventing or treating visceral obesity. Author(s): McCarty MF. Source: Medical Hypotheses. 2001 August; 57(2): 192-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11461172

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Monoclonal antibodies to avian lipoprotein lipase. Purification of the enzyme by immunoaffinity chromatography. Author(s): Gershenwald JE, Bensadoun A, Saluja A. Source: Biochimica Et Biophysica Acta. 1985 October 2; 836(3): 286-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4041471

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Monoglyceride and diglyceride lipases from human platelet microsomes. Author(s): Chau LY, Tai HH.

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Mutations in the lipoprotein lipase gene as a cause of hypertriglyceridemia and pancreatitis in Taiwan. Author(s): Jap TS, Jenq SF, Wu YC, Chiu CY, Cheng HM. Source: Pancreas. 2003 August; 27(2): 122-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12883259

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New enteric-coated high-lipase pancreatic extract in the treatment of pancreatic steatorrhea. Author(s): Malesci A, Mariani A, Mezzi G, Bocchia P, Basilico M. Source: Journal of Clinical Gastroenterology. 1994 January; 18(1): 32-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8113582

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Oral treatment with Lactococcus lactis expressing Staphylococcus hyicus lipase enhances lipid digestion in pigs with induced pancreatic insufficiency. Author(s): Drouault S, Juste C, Marteau P, Renault P, Corthier G. Source: Applied and Environmental Microbiology. 2002 June; 68(6): 3166-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12039786

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Overproduction in Escherichia coli, purification and characterization of a family I.3 lipase from Pseudomonas sp. MIS38. Author(s): Amada K, Haruki M, Imanaka T, Morikawa M, Kanaya S. Source: Biochimica Et Biophysica Acta. 2000 May 23; 1478(2): 201-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10825531

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Pancreatic adaptation to dietary lipids is mediated by changes in lipase mRNA. Author(s): Wicker C, Scheele GA, Puigserver A. Source: Biochimie. 1988 September; 70(9): 1277-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2465787

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Paracellular leakage of lipoprotein lipase across the mammary epithelium of the goat. Author(s): Azzara CD, Dimick PS. Source: Journal of Dairy Science. 1989 May; 72(5): 1159-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2745824

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Partial purification and characterization of phosphatidic acid-specific phospholipase A(1) in porcine platelet membranes. Author(s): Miyazawa D, Ikemoto A, Fujii Y, Okuyama H.

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Phospholipase C, protein kinase C, Ca/calmodulin-dependent protein kinase II, and redox state are involved in epigallocatechin gallate-induced phospholipase D activation in human astroglioma cells. Author(s): Kim SY, Ahn BH, Kim J, Bae YS, Kwak JY, Min G, Kwon TK, Chang JS, Lee YH, Yoon SH, Min do S. Source: European Journal of Biochemistry / Febs. 2004 September; 271(17): 3470-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15317582

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Phosphorylation of the rat pancreatic bile-salt-dependent lipase by casein kinase II is essential for secretion. Author(s): Pasqualini E, Caillol N, Valette A, Lloubes R, Verine A, Lombardo D. Source: The Biochemical Journal. 2000 January 1; 345 Pt 1: 121-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10600647

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Plant sources of acid stable lipases: potential therapy for cystic fibrosis. Author(s): Tursi JM, Phair PG, Barnes GL. Source: Journal of Paediatrics and Child Health. 1994 December; 30(6): 539-43. Erratum In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7865271

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Postprandial lipoprotein lipase, insulin and gastric inhibitory polypeptide responses to test meals of different fatty acid composition: comparison of saturated, n-6 and n-3 polyunsaturated fatty acids. Author(s): Zampelas A, Murphy M, Morgan LM, Williams CM. Source: European Journal of Clinical Nutrition. 1994 December; 48(12): 849-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7889893

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Precise localization of the genes for glucose phosphate isomerase (GPI), calcium release channel (CRC), hormone-sensitive lipase (LIPE), and growth hormone (GH) in pigs, using nonradioactive in situ hybridization. Author(s): Chowdhary BP, Thomsen PD, Harbitz I, Landset M, Gustavsson I. Source: Cytogenetics and Cell Genetics. 1994; 67(3): 211-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8062599

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Pretranslational regulation of the expression of the lipoprotein lipase (EC 3.1.1.34) gene by dietary fatty acids in the rat. Author(s): Murphy MC, Zampelas A, Puddicombe SM, Furlonger NP, Morgan LM, Williams CM.

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Processing of extracellular lipase of Lactobacillus plantarum: involvement of a metalloprotease. Author(s): Silva Lopes Mde F, Leitao AL, Marques JJ, Carrondo MJ, Crespo MT. Source: Fems Microbiology Letters. 1999 July 15; 176(2): 483-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10427731

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Purification and characterization of a regiospecific lipase from Aspergillus terreus. Author(s): Yadav RP, Saxena RK, Gupta R, Davidson WS. Source: Biotechnology and Applied Biochemistry. 1998 December; 28 ( Pt 3): 243-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9799723

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Purification and characterization of lipase from a raw-milk yeast (Trichosporon asteroides). Author(s): Dharmsthiti S, Ammaranond P. Source: Biotechnology and Applied Biochemistry. 1997 October; 26 ( Pt 2): 111-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9357107

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Purification and characterization of lipase from Aeromonas sobria LP004. Author(s): Lotrakul P, Dharmsthiti S. Source: Journal of Biotechnology. 1997 April 25; 54(2): 113-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9195755

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Purification and characterization of lipase from psychrophilic Acinetobacter calcoaceticus LP009. Author(s): Pratuangdejkul J, Dharmsthiti S. Source: Microbiological Research. 2000 July; 155(2): 95-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10950191

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Purification and properties of a lipase from Cephaloleia presignis (Coleoptera, chrysomelidae). Author(s): Arreguin-Espinosa R, Arreguin B, Gonzalez C. Source: Biotechnology and Applied Biochemistry. 2000 June; 31 ( Pt 3): 239-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10814595

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Purification and properties of extracellular lipase from Pseudomonas aeruginosa EF2. Author(s): Gilbert EJ, Cornish A, Jones CW. Source: J Gen Microbiol. 1991 September; 137 ( Pt 9): 2223-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1748875

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Purification and properties of lysophospholipase isoenzymes from pig gastric mucosa. Author(s): Sunaga H, Sugimoto H, Nagamachi Y, Yamashita S. Source: The Biochemical Journal. 1995 June 1; 308 ( Pt 2): 551-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7772041

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Purification and properties of the extracellular lipase, LipA, of Acinetobacter sp. RAG-1. Author(s): Snellman EA, Sullivan ER, Colwell RR. Source: European Journal of Biochemistry / Febs. 2002 December; 269(23): 5771-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444965

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Purification of extracellular lipase from Pseudomonas aeruginosa. Author(s): Stuer W, Jaeger KE, Winkler UK. Source: Journal of Bacteriology. 1986 December; 168(3): 1070-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3096967

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Purification of stearidonic acid (18:4(n-3)) and hexadecatetraenoic acid (16:4(n-3)) from algal fatty acid with lipase and medium pressure liquid chromatography. Author(s): Ishihara K, Murata M, Kaneniwa M, Saito H, Komatsu W, Shinohara K. Source: Bioscience, Biotechnology, and Biochemistry. 2000 November; 64(11): 2454-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11193415

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Purification, properties, sequencing, and cloning of a lipoprotein-associated, serinedependent phospholipase involved in the oxidative modification of low-density lipoproteins. Author(s): Tew DG, Southan C, Rice SQ, Lawrence MP, Li H, Boyd HF, Moores K, Gloger IS, Macphee CH. Source: Arteriosclerosis, Thrombosis, and Vascular Biology. 1996 April; 16(4): 591-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8624782

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Purinergic stimulation of rat cardiomyocytes induces tyrosine phosphorylation and membrane association of phospholipase C gamma: a major mechanism for InsP3 generation. Author(s): Puceat M, Vassort G. Source: The Biochemical Journal. 1996 September 1; 318 ( Pt 2): 723-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8809068

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Regulation of fatty acid 18O exchange catalyzed by pancreatic carboxylester lipase. 2. Effects of lateral lipid distribution in mixtures with phosphatidylcholine. Author(s): Muderhwa JM, Brockman HL.

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Source: Biochemistry. 1992 January 14; 31(1): 149-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1531021 •

Retinal pigment epithelial acid lipase activity and lipoprotein receptors: effects of dietary omega-3 fatty acids. Author(s): Elner VM. Source: Trans Am Ophthalmol Soc. 2002; 100: 301-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12545699

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Role of processing of the oligosaccharide chains in the affinity of lipoprotein lipase for heparin. Author(s): Masuno H, Okuda H. Source: Biochimica Et Biophysica Acta. 1994 April 14; 1212(1): 125-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8155721

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Role of protein kinase C alpha in endothelin-1 stimulation of cytosolic phospholipase A2 and arachidonic acid release in cultured cat iris sphincter smooth muscle cells. Author(s): Husain S, Abdel-Latif AA. Source: Biochimica Et Biophysica Acta. 1998 May 20; 1392(1): 127-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9593858

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Salacia reticulata and its polyphenolic constituents with lipase inhibitory and lipolytic activities have mild antiobesity effects in rats. Author(s): Yoshikawa M, Shimoda H, Nishida N, Takada M, Matsuda H. Source: The Journal of Nutrition. 2002 July; 132(7): 1819-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12097653

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Screening of lipase inhibitors from marine algae. Author(s): Bitou N, Ninomiya M, Tsujita T, Okuda H. Source: Lipids. 1999 May; 34(5): 441-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10380115

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Secretion of rat hepatic lipase is blocked by inhibition of oligosaccharide processing at the stage of glucosidase I. Author(s): Verhoeven AJ, Jansen H. Source: Journal of Lipid Research. 1990 October; 31(10): 1883-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2150412

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Short-term intake of conjugated linoleic acid inhibits lipoprotein lipase and glucose metabolism but does not enhance lipolysis in mouse adipose tissue. Author(s): Xu X, Storkson J, Kim S, Sugimoto K, Park Y, Pariza MW.

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Spinal cord of the rat contains more lipoprotein lipase than other brain regions. Author(s): Bessesen DH, Richards CL, Etienne J, Goers JW, Eckel RH. Source: Journal of Lipid Research. 1993 February; 34(2): 229-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8429258

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Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signalregulated kinase pathway. Author(s): Greenberg AS, Shen WJ, Muliro K, Patel S, Souza SC, Roth RA, Kraemer FB. Source: The Journal of Biological Chemistry. 2001 November 30; 276(48): 45456-61. Epub 2001 October 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11581251

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Structured lipids via lipase-catalyzed incorporation of eicosapentaenoic acid into borage (Borago officinalis L.) and evening primrose (Oenothera biennis L.) oils. Author(s): Senanayake SP, Shahidi F. Source: Journal of Agricultural and Food Chemistry. 2002 January 30; 50(3): 477-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11804516

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Substrate specificities of lipases from corn and other seeds. Author(s): Lin YH, Yu C, Huang AH. Source: Archives of Biochemistry and Biophysics. 1986 January; 244(1): 346-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3947065

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The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein binds lipoprotein lipase and beta-migrating very low density lipoprotein associated with the lipase. Author(s): Nykjaer A, Bengtsson-Olivecrona G, Lookene A, Moestrup SK, Petersen CM, Weber W, Beisiegel U, Gliemann J. Source: The Journal of Biological Chemistry. 1993 July 15; 268(20): 15048-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7686910

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The anti-lipase activity of shiunko on Propionibacterium acnes. Author(s): Higaki S, Morimatsu S, Morohashi M, Yamagishi T. Source: International Journal of Antimicrobial Agents. 1998 August; 10(3): 251-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9832288

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The effect of concentration of tannin-rich bean hulls (Vicia faba L.) on activities of lipase (EC 3.1.1.3) and alpha-amylase (EC 3.2.1.1) in digesta and pancreas and on the digestion of lipid and starch by young chicks. Author(s): Longstaff MA, McNab JM.

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Source: The British Journal of Nutrition. 1991 July; 66(1): 139-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1931901 •

The effect of dietary fish oil on muscle and adipose tissue lipoprotein lipase. Author(s): Herzberg GR, Rogerson M. Source: Lipids. 1989 April; 24(4): 351-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2755312

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The effect of hashish-smoking on serum levels of pancreatic lipase (EC 3.1.1.3) in man. Author(s): Dionyssiou-Asteriou A, Kalofoutis A, Maravelias C, Koutselinis A. Source: Journal of Toxicology. Clinical Toxicology. 1990; 28(2): 263-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2398524

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The enteral bioavailability of eicosapentaenoic acid and docosahexaenoic acid is as good from ethyl esters as from glyceryl esters in spite of lower hydrolytic rates by pancreatic lipase in vitro. Author(s): Krokan HE, Bjerve KS, Mork E. Source: Biochimica Et Biophysica Acta. 1993 May 20; 1168(1): 59-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8504143

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The lipolysis of chylomicrons derived from different dietary fats by lipoprotein lipase in vitro. Author(s): Botham KM, Avella M, Cantafora A, Bravo E. Source: Biochimica Et Biophysica Acta. 1997 November 30; 1349(3): 257-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9434140

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The quantitation of lipoprotein lipase mRNA in biopsies of human adipose tissue, using the polymerase chain reaction, and the effect of increased consumption of n-3 polyunsaturated fatty acids. Author(s): Murphy MC, Brooks CN, Rockett JC, Chapman C, Lovegrove JA, Gould BJ, Wright JW, Williams CM. Source: European Journal of Clinical Nutrition. 1999 June; 53(6): 441-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10403579

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Tissue-specific changes in lipid composition and lipoprotein lipase activity during the development of the chick embryo. Author(s): Speake BK, Noble RC, McCartney RJ. Source: Biochimica Et Biophysica Acta. 1993 January 10; 1165(3): 263-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8418884

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Triacylglycerol-rich lipoprotein margination: a potential surrogate for whole-body lipoprotein lipase activity and effects of eicosapentaenoic and docosahexaenoic acids. Author(s): Park Y, Jones PG, Harris WS. Source: The American Journal of Clinical Nutrition. 2004 July; 80(1): 45-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15213026

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Various dietary fibers have different effects on lipase-catalyzed hydrolysis of tributyrin in vitro. Author(s): Hendrick JA, Tadokoro T, Emenhiser C, Nienaber U, Fennema OR. Source: The Journal of Nutrition. 1992 February; 122(2): 269-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1310109

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Zinc deficiency and the activities of lipoprotein lipase in plasma and tissues of rats force-fed diets with coconut oil or fish oil. Author(s): Kettler SI, Eder K, Kettler A, Kirchgessner M. Source: The Journal of Nutritional Biochemistry. 2000 March; 11(3): 132-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10742657

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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

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

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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

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HealthGate: http://www.tnp.com/

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

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

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

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The following is a specific Web list relating to lipase; 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 Acne Rosacea Source: Healthnotes, Inc.; www.healthnotes.com Allergies Source: Integrative Medicine Communications; www.drkoop.com Autoimmune Conditions Source: Integrative Medicine Communications; www.drkoop.com Celiac Disease Source: Healthnotes, Inc.; www.healthnotes.com Celiac Disease Source: Integrative Medicine Communications; www.drkoop.com Crohn's Disease Source: Healthnotes, Inc.; www.healthnotes.com Cystic Fibrosis Source: Healthnotes, Inc.; www.healthnotes.com Cystic Fibrosis Source: Integrative Medicine Communications; www.drkoop.com Digestive Disorders Source: Integrative Medicine Communications; www.drkoop.com Food Allergy Source: Integrative Medicine Communications; www.drkoop.com Gallbladder Disease Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Prima Communications, Inc.www.personalhealthzone.com Inflammation Source: Integrative Medicine Communications; www.drkoop.com Malabsorption Syndromes Source: Integrative Medicine Communications; www.drkoop.com Migraine Headaches Source: Prima Communications, Inc.www.personalhealthzone.com

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Pancreatic Insufficiency Source: Healthnotes, Inc.; www.healthnotes.com •

Herbs and Supplements Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Aristolochia Alternative names: Snakeroot, Guaco; Aristolochia sp Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Blue-Green Algae Source: Healthnotes, Inc.; www.healthnotes.com Cinnamomum Alternative names: Cinnamon; Cinnamomum zeylanicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Curcuma Alternative names: Turmeric; Curcuma longa L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Digestive Enzymes Source: Healthnotes, Inc.; www.healthnotes.com Digestive Enzymes Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10051,00.html Feverfew Alternative names: Tanacetum parthenium Source: Healthnotes, Inc.; www.healthnotes.com Feverfew Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Grape Seed Alternative names: Vitis vinifera Source: Integrative Medicine Communications; www.drkoop.com Lipase Source: Healthnotes, Inc.; www.healthnotes.com Lipase Source: Integrative Medicine Communications; www.drkoop.com

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Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Pimpinella Alternative names: Anise; Pimpinella anisum (L) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piper Nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tanacetum Alternative names: Feverfew; Tanacetum parthenium (L.) Schultz-Bip. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Trigonella Alternative names: Fenugreek; Trigonella foenum graecum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Uncaria Asian Alternative names: Asian species; Uncaria sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Viburnum Alternative names: Cramp Bark, Highbush Cranberry; Viburnum sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Vitis Vinifera Source: Integrative Medicine Communications; www.drkoop.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 LIPASE Overview In this chapter, we will give you a bibliography on recent dissertations relating to lipase. 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 “lipase” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lipase, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Lipase 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 lipase. 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: •

Association of a variant lipase with breast milk jaundice. by SCHULTZ, GARY EDWARD, PHD from WAYNE STATE UNIVERSITY, 1977, 160 pages http://wwwlib.umi.com/dissertations/fullcit/7805224

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Chimeras of lipoprotein lipase and hepatic lipase: Localization of the apolipoprotein C-II activation site of lipoprotein lipase by McIlhargey, Trina Leann, PhD from THE UNIVERSITY OF BRITISH COLUMBIA (CANADA), 2003, 224 pages http://wwwlib.umi.com/dissertations/fullcit/NQ85390

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E. coli lipase and lysophospholipase by Nantel, Guy, PhD from UNIVERSITY OF OTTAWA (CANADA), 1977 http://wwwlib.umi.com/dissertations/fullcit/NK33712

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Early studies on the lipase homolog of the Marek's disease herpesvirus: An enzymatically inactive alpha beta hydrolase fold that may serve to bond fatty acids by Kamil, Jeremy Phillip, PhD from UNIVERSITY OF CALIFORNIA, DAVIS, 2003, 146 pages http://wwwlib.umi.com/dissertations/fullcit/3097438

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Effects of reduced free fatty acid availibility on hormone-sensitive lipase activity in human skeletal muscle during aerobic exercise by O'Neill, Marcus G., MSc from UNIVERSITY OF GUELPH (CANADA), 2003, 81 pages http://wwwlib.umi.com/dissertations/fullcit/MQ80184

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Expression and mutagenesis studies of Candida antarctica lipase B by Rotticci-Mulder, Johanna C., PhD from KUNGLIGA TEKNISKA HOGSKOLAN (SWEDEN), 2003, 110 pages http://wwwlib.umi.com/dissertations/fullcit/f204817

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Identification of novel candidate obesity genes in hepatic lipase knockout BSB mice by Farahani, Poupak, PhD from UNIVERSITY OF CALIFORNIA, DAVIS, 2003, 131 pages http://wwwlib.umi.com/dissertations/fullcit/3097962

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Induction de cytokines pro-inflammatoires dans la deficience primaire en lipase lipoproteique: Effet de la lysophosphatidylcholine (French text) by Laflamme, Nathalie, MSc from UNIVERSITE LAVAL (CANADA), 2003, 90 pages http://wwwlib.umi.com/dissertations/fullcit/MQ83070

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Les effets de l'heredite de l'exercice et de l'entrainement aerobie sur la lipogenese et la lipoproteine lipase du tissu adipeux chez l'humain by Savard, Roland, PhD from UNIVERSITE LAVAL (CANADA), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK67127

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Studies on oat, Avena sativa L. partial characterization of oat lipase : structure and biosynthesis of globulin by Matlashewski, Gregory John, PhD from UNIVERSITY OF OTTAWA (CANADA), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK64030

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The effects of caffeine and exercise on adipose cellularity, lipoprotein lipase activity, and energy substrate utilization in the rat by WILCOX, ANTHONY ROBERT, PHD from UNIVERSITY OF MASSACHUSETTS, 1980, 148 pages http://wwwlib.umi.com/dissertations/fullcit/8101410

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The isolation and partial characterization of a deacylase from wheat germ lipase Studies on the products of enzymic deacylation of some mono-and disaccharide esters by Fink, Anthony L, ADVDEG from QUEEN'S UNIVERSITY AT KINGSTON (CANADA), 1967 http://wwwlib.umi.com/dissertations/fullcit/NK01669

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Variants in the lipoprotein lipase gene and paraoxonase gene and risk of preeclampsia by Zhang, Cuilin, PhD from UNIVERSITY OF WASHINGTON, 2003, 93 pages http://wwwlib.umi.com/dissertations/fullcit/3111141

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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. PATENTS ON LIPASE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “lipase” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lipase, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Lipase By performing a patent search focusing on lipase, 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

8Adapted

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

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on lipase: •

Cosmetic product containing enzymes Inventor(s): Golz-Berner; Karin (Monaco, DE), Zastrow; Leonhard (Monaco, DE) Assignee(s): Coty B.V. (NL) Patent Number: 6,551,606 Date filed: December 5, 2001 Abstract: The invention relates to a cosmetic product that contains enzymes and has an intensive skin action, especially a regenerative effect The inventive cosmetic product contains 0.01 to 5 wt. % of a concentrate of the coconut milk of Cocos nucifera, containing peroxidase, lipase and protease; 0.1 to 10 wt. % of a plant milkwater, the plants being selected from the following group: banana, dandelion, convolvus, poppy, soya and mixtures thereof; and 0.01 to 5 wt. % of a glycerol extract of a mixture consisting of honey, rice hulls, rice hull oil and/or rice germ oil; with the remainder consisting of cosmetic auxiliary agents, active agents and carrier substances. Excerpt(s): This application is a 371 of PCT/DE00/01891, submitted Jun. 8, 2000. The invention relates to a cosmetic product that contains enzymes and has an intensive skin action, especially a regenerative effect. There is already a number of known cosmetic products which are produced using animal milk or a derivate of lactic acid. DE-A-44 08 258, for example, discloses an oil/water emulsion containing whole milk, which emulsion contains polyethoxylated vitamin E as an emulsifier and has a viscosity of less than 100 Pa.multidot.s. DE-A-195 37 297 discloses cosmetic preparations containing growth factors which are produced from fresh or pasteurized milk and colostrum of cows and mares. Furthermore, EP-A-908171 discloses a dry, plant-based cleansing composition, in which various dried and crushed plants, which serve as detergent, foaming agent, foam enhancer, pigment and conditioner, are combined in a powder, Cocos nucifera being used as a foam enhancer. Web site: http://www.delphion.com/details?pn=US06551606__

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Diaper dermatitis preventative medication and a method for making and using same Inventor(s): Moehring; Richard J. (Houston, TX) Assignee(s): Mentis Technologies, L.C. (Houston, TX) Patent Number: 6,592,879 Date filed: August 27, 2002 Abstract: The invention discloses a composition for the prevention and treatment of diaper dermatitis which includes an effective amount of an anti-lipase agent and/or an anti-protease agent in a suitable vehicle. The composition is designed to maintain an effective amount of the lipase and/or protease inhibitors and to be applied to tissues susceptible to fecal enzyme insult. The invention also discloses a composition for the prevention and treatment of diaper dermatitis which includes an effective amount of a sacrificial lipase substrate and/or a sacrificial protease substrate in a suitable vehicle. The composition is designed to maintain an effective amount of the substrates and to be applied to tissues susceptible to fecal enzyme insult. The present invention also discloses a combination or mixtures of an effective amount of an anti-lipase agent and/or an anti-

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protease agent in a suitable vehicle and an effective amount of a sacrificial lipase substrate and/or a sacrificial protease substrate in a suitable vehicle. Excerpt(s): The present invention relates to a composition for the prophylaxis and/or treatment of diaper dermatitis or similar dermal irritation and methods for making and using the composition. More particularly, the present invention relates to a composition including an enzyme inhibitor system, a sacrificial substrate system or a combined system for the prophylaxis and/or treatment of tissue irritation due to enzyme activity, especially protease and lipase enzyme activity, and methods for making and using such compositions. The compositions of the present invention are especially useful in inhibiting the activity of lipase and protease enzymes present in expressed feces that cause diaper dermatitis or similar dermal conditions or in tissues exposed to bodily fluids or any fluid containing lipase and protease enzymes or the exposure of tissues to any composition (solid, liquid, emulsion, dispersion, etc.) containing lipase and protease enzymes. Diaper dermatitis is a phenomenon frequently encountered by parents of small children or by patients in nursing homes who are required to wear a diaper. Although the dermatitis is treatable, occurrence and persistence often results in unhappy children and sleep deprived parents. In severe cases, it results in painful decubitus ulcers. Many ointments and powders exist on the market for treating and preventing diaper dermatitis, but most function by merely forming a barrier between the skin and expressed feces. Web site: http://www.delphion.com/details?pn=US06592879__ •

Enzymatic methods for polyunsaturated fatty acid enrichment Inventor(s): Breton; Gildas (Penanguer, Concarneau, FR F-29900) Assignee(s): none reported Patent Number: 6,537,787 Date filed: March 13, 1998 Abstract: A process for obtaining polyunsaturated fatty acid concentrates comprising subjecting a fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), to a selective enzymatic hydrolysis in position 1, 3 or 2, to obtain a mixture of free fatty acids, monoglycerides and diglycerides, separating the constituents of this mixture, collecting the free fatty acids which are purified by crystallization from urea, to increase the EPA and DHA content, decomplexing the isolated fatty acids by an interesterification between the free fatty acids concentrated into polyunsaturated fatty acids and the crude oil, in the presence of a lipase specific for position or steric hindrance, to obtain a mixture enriched with polyunsaturated fatty acid triglycerides which is separated and freed from the free fatty acids and a process for enrichment with polyunsaturated fatty acids (EPA, DHA) of phospholipids by an enzymatic route, as well as in the synthesis of monoacylglycerols of polyunsaturated fatty acids of the n3 series, by enzymatic synthesis starting with a 1,2-dialkylene glycerol which are useful in the domain of foodstuffs, cosmetics and pharmacology. Excerpt(s): A subject of the present invention is new processes for the production of polyunsaturated fatty acid esters in a pure or concentrated form. A more particular subject of the invention is processes for the production of esters of polyunsaturated fatty acids of the.omega.-3 series starting with glycerides of fatty acids extracted from fish oils, phospholipids, or 1,2-dialkyene glycerols, using an enzymatic treatment. A specific subject of the invention is a process for the production of glycerides of polyunsaturated

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fatty acids in a pure or concentrated form from fish oil or other sources, characterized in that it allows, by enzymatic treatment, a mixture to be obtained containing a high content of docosahexaenoic acid (DHA) and/or of eicosapentaenoic acid (EPA), which can reach, in the case of fish oils, 60%. Web site: http://www.delphion.com/details?pn=US06537787__ •

Esterification or hydrolysis with substrate treated un-dried immobilized lipolytic enzyme Inventor(s): Kase; Minoru (Ibaraki, JP), Komatsu; Toshiteru (Ibaraki, JP), Shimizu; Masami (Ibaraki, JP), Shimizu; Masao (Ibaraki, JP) Assignee(s): Kao Corporation (Tokyo, JP) Patent Number: 6,716,610 Date filed: December 2, 1999 Abstract: A lipolytic enzyme such as lipase is adsorbed on a porous anion-exchange resin carrier to obtain an immobilized enzyme without drying. The un-dried immobilized enzyme is contacted with a fat or oil for a time which may be about 2 hours to about 24 hours to stabilize the immobilized enzyme, and the immobilized enzyme is recovered from the fat or oil. The recovered immobilized enzyme is then used for esterifying or hydrolyzing a substrate. Water content of the un-dried immobilized enzyme may be 20% or more be weight such as 20-60%. Prior to immobilization, the resin carrier may be treated with a lypophylic aliphatic acid which preferably has 8 to 18 carbons. Excerpt(s): The present invention relates to a process for preparing an immobilized enzyme showing a high activity with a less loss in the enzyme activity, which is used for hydrolysis of fats and oils, ester-exchange of fats and oils, and esterification of aliphatic acids and alcohols. The term of "fats and oils" means an inclusion of a fat, an oil, a lard, a grease and so on. In hydrolyzing fats and oils by a lipolytic (or fat and/or oildecomposing) enzyme, an immobilized enzyme prepared by immobilizing a lipolytic enzyme onto an inorganic or organic carrier is used for efficient use of the enzyme. To raise the absorptivity of the enzyme onto a carrier and to improve an enzyme activity, various studies have been made, and for example, JP-A 9-257 discloses a process for producing an immobilized enzyme carrier prepared by immobilizing a lipase onto an inorganic carrier treated with a silane coupling agent having a special functional group, washing and drying it, and impregnating it with an aliphatic acid. Even by this method, however, the amount of the adsorbed enzyme and the enzyme activity remain still insufficient. Further, an immobilized enzyme prepared by immobilizing a lipolytic enzyme called lipase onto a carrier is used as an enzyme mainly for use in reactions for the object of ester-exchanging (ester-interchanging or transesterifying) fats and oils and esterifying aliphatic acids and alcohols. These reactions are advantageously conducted at concentrations of water as low as possible (1000 ppm or less) to inhibit hydrolysis, and thus the immobilized enzyme is forcibly dried to give only several % water content in the carrier, since the immobilized enzyme is prepared. Web site: http://www.delphion.com/details?pn=US06716610__

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•

Expression methods Inventor(s): Dalrymple; Michael (Dalgety Bay, GB), Lundberg; Lennart (Billdal, SE), Stromqvist; Mats (Ume.ang., SE) Assignee(s): AstraZeneca AB (Sodertalje, SE) Patent Number: 6,525,241 Date filed: July 18, 1999 Abstract: The present invention relates to human bile salt-stimulated lipase (BSSL) obtainable from transgenic sheep. The invention further relates to transgenic sheep whose germ cells and somatic cells contain a recombinant nucleotide molecule comprising a nucleotide sequence encoding for human BSSL. The invention also relates to methods for producing said transgenic animals, as well as to methods for producing human BSSL derived from transgenic animals. In addition, the invention provides the use of compositions comprising BSSL in the treatment of diseases relating to exocrine pancreatic insufficiency, and for improvement of the utilization of dietary lipids in preterm born infants. Excerpt(s): Bile Salt-Stimulated Lipase (BSSL) is the major lipolytic activity present in human milk (Wang & Johnson, 1983; Wang & Hartsuck, 1993). As its name implies, the enzyme is not active in the milk but is activated in the intestine by bile salts. In mammals a similar enzyme activity is also secreted from the pancreas into the intestine. The cDNA sequences for both the mammary and pancreatic enzyme are identical indicating that they are the product of a single gene (Reue et al., 1991; Lidberg et al., 1992). BSSL shares with other pancreatic lipases a triacylglycerol hydrolase activity but BSSL is the only intestinal lipase which hydrolyses cholesterol ester and other fatty acid esters, such as vitamin A ester. The protein is stable to both proteases and the acid environment in infant stomachs. These unique activities and the large quantity of BSSL in human milk suggest that this enzyme is physiologically important. The cDNA sequence (SEQ ID NO: 2) and deduced amino acid sequence (SEQ ID NOS: 3and 4) of BSSL have been disclosed by Nilsson et al. (1990); in U.S. Pat. No. 5,200,183 (Oklahoma Medical Research Foundation); and in WO 91/18923 (Astra AB). Human BSSL is a glycoprotein consisting of 772 amino acids. The C-terminal portion is composed of 16 repeats each of 11 amino acids having consensus PVPPTGDSGAP (SEQ ID NO: 5). The genomic DNA sequence (SEQ ID NO: 1) encoding human BSSL is disclosed by Lidberg et al. (1992) in U.S. Pat. No. 5,616,483 (Astra AB). Web site: http://www.delphion.com/details?pn=US06525241__

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Fatty acid polyol ester-coated lipase complex immobilized on insoluble matrix Inventor(s): Basheer; Sobhi (Sakhnine, IL) Assignee(s): Enzymotec, Ltd. (Nazareth Illit, IL) Patent Number: 6,605,452 Date filed: March 23, 1999 Abstract: A lipase preparation is prepared containing a surfactant-coated lipase complex immobilized onto an insoluble matrix. A preferred surfactant is a fatty acid polyol ester such as sorbitan monostearate (SMS). The lipase preparation may be provided in granulated form or in an organic solvent, and can be used in esterifying, inter-esterifying, trans-esterifying and alcoholysing reactions with no added water. The

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lipase preferably has 1,3-positional specificity with respect to triacylglycerols, and the insoluble matrix may be modified with a fatty acid derivative. A lipase in aqueous medium is contacted with a surfactant to coat the lipase with the surfactant, and the coated lipase is immobilized onto an insoluble matrix to produce the lipase preparation which may be dried such as by freeze drying. Alternatively, the lipase may be first contacted with the insoluble matrix, and thereafter with the surfactant. Excerpt(s): The present invention relates to an insoluble matrix immobilized surfactantcoated lipase complex, to a method of preparing same and to the use of same as a biocatalyst for catalyzing, for example, inter- and/or trans-esterification of oils and fats in hydrophobic organic media. The novel procedures include two steps. In the first step, the enzyme is activated by being coated with a surfactant. In the second step, the enzyme is immobilized on the matrix of choice. These steps can be executed in any order. Enzymatic modification of the structure and composition of oils and fats is of great industrial and clinical interest. This process is accomplished by exploiting regiospecific lipases in inter-esterification and/or trans-esterification reactions utilizing fats or oils as substrates (Macrea, A. R., 1983, J. Am. Oil Chem. Soc. 60: 291-294). Using an enzymatic process, it is possible to incorporate a desired fatty acyl group on a specific position of a triacylglycerol molecule, whereas conventional chemical inter-esterification does not possess regio-specificity. Conventionally, chemical reactions are promoted by sodium metal, sodium alkoxide or cobalt chloride that catalyze acyl migration among triglyceride molecules, leading to the production of triglycenrdes possessing randomly distributed fatty acyl residues (Erdem-Senatalar, A., Erencek, E. and Erciyes, A. T., 1995, J. Am. Oil Chem. Soc. 72: 891-894). Web site: http://www.delphion.com/details?pn=US06605452__ •

Gastric emptying-promoting composition Inventor(s): Kondo; Takaharu (Kani, JP) Assignee(s): Amano Pharmaceutical Co., Ltd. (Aichi, JP) Patent Number: 6,656,464 Date filed: December 21, 1998 Abstract: Compositions having an effect of promoting gastric emptying. These compositions comprise a lipase which was found to have an effect of promoting gastric emptying together with lipase activity-free ingredient(s) acting on the digestive tracts such as a prokinetic, a histamine H.sub.2 receptor antagonist, a proton pump inhibitor and/or a stomachic ingredient. They are efficaciously employed as medicaments for ameliorating or treating chronic gastrointestinal symptoms such as sinking feelings, heartburn and heaviness in the stomach, i.e., complaints about the digestive tracts. Excerpt(s): This invention relates to compositions having an effect of promoting the gastric emptying. More particularly, it relates to medicaments containing a lipase preparation which is a digestive enzyme. The medicaments of the present invention are efficaciously used in ameliorating or treating chronic gastrointestinal symptoms such as sinking feelings, heartburn and heaviness in the stomach, i.e., complaints about the digestive tracts. Even healthy people often notice subjective gastric symptoms (sinking feelings, heartburn, anorexia, etc.) in the everyday life. These symptoms are caused by stress, overeating, excessive intake of alcoholic drinks and intake of drugs. Moreover, it is frequently observed that the stress of the complicated current social structure or side effects of medicaments result in chronic gastrointestinal symptoms such as sinking

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feelings and heaviness in the stomach, i.e., complaints about the digestive tracts, which is now a serious social problem. In the present aging society, furthermore, the aged are largely affected by the above-mentioned problem. Web site: http://www.delphion.com/details?pn=US06656464__ •

Human lipase proteins, nucleic acids encoding them, and uses of both of these Inventor(s): Kapeller-Libermann; Rosana (Chestnut Hill, MA), Khodadoust; Mehran (Chestnut Hill, MA) Assignee(s): Millennium Pharmaceuticals, Inc. (Cambridge, MA) Patent Number: 6,558,936 Date filed: October 1, 1999 Abstract: The invention provides isolated nucleic acids encoding human lipase proteins and fragments, derivatives, and variants thereof. These nucleic acids and proteins are useful for diagnosis, prevention, and therapy of a number of human and other animal disorders associated, for example, with aberrant lipid metabolism or aberrant pancreatic activity. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides, and antibodies. Diagnostic, prognostic, screening, and therapeutic methods involving use of compositions of the invention are also provided. The nucleic acids and polypeptides of the present invention are useful as modulating agents in regulating a variety of cellular processes relating to mono-, di-, and triglyceride metabolism and pancreatic function. Excerpt(s): Lipids are esters of long chain fatty acids (generally C.sub.14 to C.sub.24 saturated and unsaturated fatty acids in animal fats) and polyols such as glycerol, glycerol phosphates, alkyl glyceryl ethers, glycerol phosphoryl-choline, glycerol phosphoryl-serine, glycerol phosphoryl-ethanolamine, and the like. Lipids, in the form of cell membranes and fats, for example, constitute a significant proportion of animal body weight (e.g., about 5% to 25% of body weight in normal humans). Lipids are not water-soluble, and generally do not cross biological membranes efficiently by simple diffusion. Dietary lipids are taken up primarily by hydrolysis of fatty acyl moieties from their corresponding polyol moiety and diffusion of the two moieties across the gut wall (although limited uptake of intact lipids occurs). Following absorption, lipids are reformed by reestablishment of ester bonds between polyol and fatty acyl moieties, and lipids are delivered throughout the body in esterified form (generally in lipoproteincontaining particles such as chylomicrons, very low, intermediate, low, and high density lipoprotein particles, and the like). Prior to uptake by cells (either for storage or for metabolism), lipids must again be hydrolyzed in order to facilitate passage across the cell membrane. Thus, enzymes which catalyze formation and hydrolysis of the ester bonds between fatty acyl moieties and polyol moieties of lipids must be present at several physiological locations, and the particular activities catalyzed by these enzymes (`lipases` ) varies depending on the physiological location and function of the enzyme. A number of lipase enzymes have been characterized in various organisms, including in humans. However, it is far from clear that all physiologically relevant lipases have been discovered or characterized. The present invention provides novel nucleotide and amino acid sequence information corresponding to one or more human lipases.

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Web site: http://www.delphion.com/details?pn=US06558936__ •

Immobilization of enzymes on particulate porous carriers for use in organic mediums Inventor(s): Christensen; Morten Wurtz (Lyngby, DK), Kirk; Ole (Virum, DK), Pedersen; Christian (Roedovre, DK) Assignee(s): Novozymes A/S (Bagsvaerd, DK) Patent Number: 6,582,942 Date filed: August 29, 2000 Abstract: An immobilized enzyme is prepared for use in organic mediums essentially devoid of free water. An enzyme-containing liquid medium is contacted with a particulate porous carrier which preferably has a particle size of 200-1000.mu.m and a surface area of 20-1000 m.sup.2 /g to adsorb the enzyme on the carrier, and volatile components of the liquid medium contained by the carrier are removed. The carrier may have a hydrophilic surface, and an amount of liquid medium is used to prevent agglomeration of the carrier. Alternatively, the carrier has a hydrophobic surface, and the addition of a hygroscopic substance suppresses agglomeration of the carrier by absorbing excess liquid. The hygroscopic substance may be removed during the removal of volatile components. Contacting of the enzyme-containing liquid and carrier can be in a fluidized bed where immobilization and removing volatile components are conducted simultaneously, or contacting can be in mixer followed by removing volatile components in a fluidized bed. The enzyme-containing liquid may be atomized onto the carrier in the fluidized bed or in the mixer. Enzymes immobilized include lipase, and the immobilized lipase can be used in trans-esterification reactions. Excerpt(s): The invention relates to a process for producing an immobilized enzyme preparation for use in a mainly organic medium essentially devoid of free water, and use of the immobilized enzyme preparation for organic synthesis. Immobilized enzymes are known to be used for organic synthesis. The most commonly immobilized enzymes are lipases used for esterification reactions in mainly organic media essentially devoid of free water. Web site: http://www.delphion.com/details?pn=US06582942__

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Immobilizing lipase by adsorption from a crude solution onto nonpolar polyolefin particles Inventor(s): Friedrich; Thomas (Darmstadt, DE), Sturmer; Rainer (Rodersheim-Gronau, DE) Assignee(s): BASF Aktiengesellschaft (Ludwigshafen, DE) Patent Number: 6,596,520 Date filed: July 6, 2000 Abstract: Immobilized lipase is prepared by adsorbing lipase from a crude lipase solution onto polyolefin particles such as polypropylene particles which are nonpolar. The crude solution may be a cell-free culture broth. Lipase sources include Pseudomonas burkholderia and Pseudomonas aeruginosa. Uses of the immobilized lipase include enantioselective conversion of substrates such as enantioselective acylating or hydrolyzing.

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Excerpt(s): The present invention relates to a process for preparing immobilized lipase, to the immobilized lipase itself and to a process for enzyme-catalyzed conversion in the presence of the immobilized lipase. Lipases can be used in solution as enzymatic catalysts for converting substrates. Immobilized lipases are distinguished from free lipases by having an increased stability and useful life on carrying out the reaction continuously and batchwise, and by easy recovery of the catalytically active species in batchwise reactions. It is known to immobilize lipases by adsorption onto a solid support. It is also known to prepare immobilized lipases by contacting polyolefin particles with an aqueous solution of a purified lipase. Web site: http://www.delphion.com/details?pn=US06596520__ •

Lipase inhibiting compositions Inventor(s): de Smidt; Passchier Christiaan (Pamplona, ES), Hadvary; Paul (Biel-Benken, CH), Lengsfeld; Hans (Basel, CH), Schmid; Marcel (Reinach, CH), Small; Donald MacFarland (Quincy, MA), Steffen; Hans (Liestal, CH), Tardio; Joseph (St. Louis, FR) Assignee(s): Hoffman-La Roche Inc. (Nutley, NJ) Patent Number: 6,703,369 Date filed: September 13, 2000 Abstract: A pharmaceutical composition contains at least one inhibitor of lipases and at least one fatty acid ester of polyol. In this composition, the fatty acid ester has a melting point above the body temperature and the polyols are chosen from the group consisting of sugars, sugar derivatives, and mixtures thereof. Excerpt(s): The present invention relates to pharmaceutical compositions comprising at least one lipase inhibitor. Lipase inhibitors include lipstatin and orlistat. The latter is also known as tetrahydrolipstatin or THL and is derived from a natural product excreted by Streptomyces toxytricini. This class of compounds was found to exhibit in vitro as well as in vivo activity against various lipases, such as lingual lipase, pancreatic lipase, gastric lipase, and carboxylester lipase. Its use for the control or prevention of obesity and hyperlipidemia is described, for instance, in U.S. Pat. No. 4,598,089. Orlistat is currently administered at doses of 120 mg per meal and dosing is independent of the body mass of the human subject. Orlistat acts locally in the gastrointestinal (GI) tract and prevents lipase from digesting triglycerides and subsequently inhibits the formation of absorbable lipid degradation products. For this reason, systemic availability of the lipase inhibitors is not required; instead, local residence in the gastrointestinal tract is preferred. Web site: http://www.delphion.com/details?pn=US06703369__

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Lipase variant Inventor(s): Bojsen; Kirsten (Hellerup, DK), Borch; Kim (Copenhagen, DK), Halkier; Dorte Aaby (Birkerod, DK), Patkar; Shamkant Anant (Lyngby, DK), Svendsen; Allan (Horsholm, DK), Vind; Jesper (Lyngby, DK) Assignee(s): Novozymes A/S (Bagsvaerd, DK) Patent Number: 6,624,129 Date filed: August 1, 2000

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Abstract: The present invention relates to lipase variants having at least 90% identity to the wild-type lipase derived from Humicola lanuginosa strain DSM 4109 and having a certain distribution of electrically charged amino acids. The present invention also relates to detergents comprising such lipases. Excerpt(s): The present invention relates to lipase variants suited for use in detergent compositions, particularly detergents with a high content of anionic surfactant. More particularly, the invention relates to variants of the wild-type lipase from Humicola lanuginosa strain DSM 4109. For a number of years, lipases have been used as detergent enzymes to remove lipid or fatty stains from clothes and other textiles, particularly a lipase derived from Humicola lanuginosa (EP 258 068 and EP 305 216) sold under the tradename Lipolase.RTM. (product of Novo Nordisk A/S). There is an ever existing need for providing novel lipases with improved properties, in particular improved washing properties in commercial detergents, including detergents with a high content of anionic surfactants. The present invention relates to such novel lipases. Web site: http://www.delphion.com/details?pn=US06624129__ •

Lipase-catalysed esterification of marine oil Inventor(s): Haraldsson; Gudmundur G. (Reykjavik, IS), Kristiansson; Bj.o slashed.rn (Reykjavik, IS), Thorstad; Olav (Heistad, NO) Assignee(s): Norsk Hydro ASA (Oslo, NO) Patent Number: 6,518,049 Date filed: November 2, 2001 Abstract: Marine oil compositions which contain EPA and DHA as free acids are esterified with glycerol in the presence of a lipase catalyst under reduced pressure and essentially organic solvent-free conditions to form a free fatty acid fraction enriched in at least one of EPA and DHA. Excerpt(s): This invention relates to the lipase catalysed esterification of marine oils. It is well known in the art to refine oil products of various kinds, including marine oils, with the aid of lipase catalysts whose specificity under the refining conditions employed enhances the recovery of a desired product. For example, in PCT/WO95/00050 we disclosed a process for treating an oil composition containing saturated and unsaturated fatty acids in the form of triglycerides to transesterification reaction conditions with a C.sub.1-6 alcohol such as ethanol under substantially anhydrous conditions in the presence of a lipase active to preferentially catalyse the transesterification of the saturated and monounsaturated fatty acids. With the preferred lipases, Pseudomonas sp. lipase (PSL) and Pseudomonas fluorescens lipase (PFL) it was possible to prepare from marine oil sources concentrates containing more than 70% by weight of the commercially and therapeutically important omega-3 polyunsaturated fatty acids EPA (eicosapentaenoic acid, C20:5) and DHA (docosahexaenoic acid, C22:6) in the form of glycerides. Web site: http://www.delphion.com/details?pn=US06518049__

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Method of producing activated lipase Inventor(s): Ichikawa; Sosaku (Ibaraki, JP), Maruyama; Tatsuo (Ibaraki, JP), Nabetani; Hiroshi (Ibaraki, JP), Nakajima; Mitsutoshi (Ibaraki, JP), Seki; Minoru (Tokyo, JP) Assignee(s): Bio-Oriented Technology Research Advancement Institution (), Japan as represented by Director of National Food Research Institute (Ibaraki, JP), Ministry of Agriculture, Forestry and Fisheries (Tokyo, JP) Patent Number: 6,528,293 Date filed: October 12, 1999 Abstract: A method is disclosed for activating a lipase by adding a solution of lipase in an aqueous buffer at a pH near neutrality to an organic phase, e.g., tetradecane. Under these conditions lipase is activated as a function of an organic-and-water boundary surface between the organic and water phases. The lipase that is activated in this manner remains active even after lyophilization to remove the water and the organic phase. This activated lipase efficiently catalyzes a fat reforming reaction in non-aqueous and nano-aqueous conditions. Excerpt(s): The present invention relates to a method of activating of an enzyme such as lipase, etc., to reaction of such activated enzyme including reformation of fat, and further to a method of deactivating the enzyme once it is activated. Conventionally, the production of many useful products has been achieved with use of enzymes. In particular, lipase was widely used for reforming fat so as to produce edible oil, soap, glycerin, dairy or milk products, etc., because of the versatility thereof. Today where resources, energy, and ecological problems are discussed daily on a global scale, many expectations are applied to efficient and safe production of important materials (i.e., fatty acids, etc.) in the chemical industry, as well as to high-performance materials to which much attention is paid in the fields of pharmaceuticals and foodstuffs, with the use of the enzyme which can be represented by lipase. Web site: http://www.delphion.com/details?pn=US06528293__

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Method of reducing gastrointestinal side effects associated with orlistat treatment Inventor(s): Barbier; Pierre (Rixheim, FR), Hadvary; Paul (Biel-Benken, CH), Lengsfeld; Hans (Basel, CH) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 6,756,364 Date filed: July 25, 2001 Abstract: A pharmaceutical combination or composition containing a lipase inhibitor, preferably orlistat, and a bile acid sequestrant is useful for treating obesity. Excerpt(s): The present invention relates to pharmaceutical combinations, compositions and methods for treating obesity. Bile acids are synthesized in the liver and enter the bile as glycine and taurine conjugates. They are released in salt form in bile during digestion and act as detergents to solubilize and consequently aid in digestion of dietary fats. Following digestion, bile acid salts are mostly reabsorbed in the ileum, complexed with proteins, and returned to the liver through the hepatic portal vein. The small amount of bile acid salts which are not reabsorbed by active transport are excreted via the distal ileum and large intestine as a portion of fecal material. Reducing reabsorption of bile acids within the intestinal tract can lower levels of bile acid circulating in the

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enterohepatic system thereby potentially reducing emulsification in the upper intestinal tract of dietary fat and reducing intestinal absorption of fat soluble drugs. One method of reducing the amount of bile acids that are reabsorbed, is oral administration of compounds that sequester the bile acids within the intestinal tract and cannot themselves be absorbed. Orlistat (also known as tetrahydrolipstatin and sold under the brand name XENICAL.RTM.) is a potent inhibitor of gastrointestinal lipases, i.e. lipases that are responsible for breaking down ingested fat (gastric lipase, carboxylester lipase, pancreatic lipase). As a consequence of this, unabsorbed fat is excreted in the feces. Pancreatic lipase is the key enzyme for the hydrolysis of dietary triglycerides. Triglycerides that have escaped hydrolysis are not absorbed in the intestine. Pharmacological studies with human patients demonstrate potent inhibition of fat absorption and medically relevant reduction of body weight was achieved using lipase inhibitors. However, in a subgroup of the patients, unpleasant gastrointestinal side effects such as oily spotting, fatty/oily stools, fecal urgency, increased defecation and fecal incontinence are observed. Accordingly, there is a need in the art for lipase inhibiting compositions that minimize or suppress the side effects caused by inhibitors of digestive lipases. Web site: http://www.delphion.com/details?pn=US06756364__ •

Method of stabilizing graham flour, and cracker produced from said flour Inventor(s): Adrianson; Tim Michael (Oak Ridge, NJ), Gannon; Diane Louise (Perrysburg, OH), Howey; Edward Douglas (Toledo, OH), Levine; Harold Ira (Morris Plains, NJ), Mozeke; Patricia Ann (Bedminster, NJ), Slade; Louise (Morris Plains, NJ), Wilhelm; Carolyn Louise (Hackettstown, NJ) Assignee(s): Kraft Foods Holdings, Inc. (Northfield, IL) Patent Number: 6,616,957 Date filed: November 28, 2000 Abstract: A process is provided for making reduced fat, low fat or no-fat graham-based crackers and flour for the production thereof. The process for making the flour includes providing whole wheat berries having a moisture content of from about 15% by weight to about 20% by weight, radiating the berries with infrared (IR) energy, optionally maintaining the berries at an elevated temperature of from about 80.degree. C. to about 110.degree. C. for a period of time up to about one hour, and cooling, drying and comminuting the treated berries. The moisture content of the berries can be adjusted by moistening or tempering the berries prior to treatment with IR energy. The moisture content, optional tempering conditions, amount of irradiated IR energy, the elevated temperature, and the various treatment periods are sufficient to inactivate lipase and lipoxygenase in the berries yet insufficient to gelatinize more than about 20% of the starch in the berries. The graham flour has excellent shelf-life stability, and can be used to obtain machinable doughs on a mass production, continuous basis. Baked goods made from the flour have a surprisingly crunchy texture. Excerpt(s): The present invention relates to processes for making graham-based flours which exhibit low rancidity and extended shelf-life and to baked goods having a crunchy texture made from such flours. The present invention also relates to reduced fat, low fat, or no-fat baked goods, such as graham crackers and snacks, produced from such flours. Whole cereal grains and graham flour provide a high dietary fiber content but also provide natural lipids and enzymes, such as lipase and lipoxygenase (LPO), which may deleteriously interact during storage. The interaction of the lipids and

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enzymes can lead to rancidity problems such as off-flavors and odors in baked goods made from graham flour. Generally, to avoid rancidity problems in baked goods, graham flour is employed which is less than about ten days old. Rancidity in cereal products may be due to hydrolytic (enzymatic) or oxidative degradation reactions, or both. Often, hydrolysis may predispose products to subsequent oxidative rancidity. Nature has provided a number of protective features in seeds to prevent rancidity and spoilage, enabling seeds to survive periods of adverse conditions before attaining an appropriate environment for germination and growth. Rancidity is less likely to develop when lipid materials, for example, seed oil, are unable to interact with reactants or catalysts such as air and enzymes. One protective feature in cereal grains is the provision of separate compartments for storing lipids and enzymes so that they cannot interact. Web site: http://www.delphion.com/details?pn=US06616957__ •

Method of treating high plasma cholesterol levels Inventor(s): Hadvary; Paul (Biel-Benken, CH), Lengsfeld; Hans (Basel, CH), Steffen; Hans (Liestal, CH) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 6,562,329 Date filed: July 25, 2001 Abstract: A method prevents or treats diseases associated with high plasma cholesterol levels. In addition, this method reduces plasma cholesterol levels. The method comprises administering a lipase inhibitor, e.g. orlistat, and a pharmaceutically acceptable bile acid sequestrant. Excerpt(s): The present invention relates to a new method for the prevention and treatment of diseases associated with high plasma cholesterol levels (hypercholesterolemia). Bile acid sequestrants have been proposed for use in lowering circulating blood cholesterol levels. Biologically, cholesterol is eliminated from the body by conversion to bile acids and excretion as neutral steroids. Bile acids are synthesized from cholesterol in the liver and enter the bile as glycine and taurine conjugates. They are released in salt form in bile during digestion and act as detergents to solubilize and consequently aid in digestion of dietary fats. Following digestion, bile acid salts are mostly reabsorbed in the ileum, complexed with proteins, and returned to the liver through hepatic portal veins. The small amount of bile acid salts which are not reabsorbed by active transport are excreted via the distal ileum and large intestine as a portion of fecal material. Bile acids are synthesized from cholesterol transported in lipoproteins in the liver. Therefore, reabsorption of bile acids, which can be present as the corresponding salts or conjugates, from the intestine conserves lipoprotein cholesterol in the bloodstream. As such, reducing reabsorption of bile acids within the intestinal tract can lower levels of bile acid circulating in the enterohepatic system thereby promoting replacement of bile acids through synthesis from cholesterol, in the liver. The result is a lowering of circulating blood cholesterol levels. One method of reducing the amount of bile acids that are reabsorbed, is oral administration of compounds that sequester the bile acids within the intestinal tract and cannot themselves be absorbed. The sequestered bile acids consequently are excreted. As a consequence of gastrointestinal lipase inhibition, unabsorbed fat is egested in the faeces. Pancreatic lipase is the key enzyme for the hydrolysis of dietary triglycerides. Triglycerides, which have escaped hydrolysis are not absorbed in the intestine. Orlistat

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has been shown in animal models to inhibit fat absorption and to reduce body weight. In pharmacological studies with humans potent inhibition of fat absorption was demonstrated. Web site: http://www.delphion.com/details?pn=US06562329__ •

Nutritional composition for improving the efficacy of a lipase inhibitor Inventor(s): Portman; Robert (Fair Haven, NJ) Assignee(s): Pacific Health Laboratories, Inc. (Woodbridge, NJ) Patent Number: 6,558,690 Date filed: December 14, 2001 Abstract: A nutritional intervention composition is provided for enhancing the efficacy of an orally administered lipase inhibitor comprising a protein component of at least a glycomacropeptide or caseinmacropeptide, at least one C.sub.12-18 fatty acid comprising at least oleic acid and a fiber preferably comprising both soluble and insoluble fibers. The composition is administered concurrently with the lipase inhibitor to negate the action of the latter in inhibiting the release of cholecystokinin (CCK) which, in turn, reduces the feeling of satiety and stimulates appetite. These effects are all countered by the subject compositions which stimulate release of CCK and increase the level of bile in the intestine. These effects achieved by the subject nutritional intervention compositions, while not directly increasing the effectiveness of the lipase inhibitor, nonetheless enhance its efficacy. Excerpt(s): The present invention relates to a nutritional composition that is taken with a lipase inhibitor prior to the consumption of a meal which enhances the efficacy of the lipase inhibitor by increasing CCK levels and enhancing and extending post meal satiety. Lipase inhibitors are being prescribed for weight reduction in obese patients. A lipase inhibitor functions by inhibiting gastric and pancreatic lipases, thereby rendering them temporarily unavailable to hydrolyze dietary fat in the form of triglycerides into absorbable free fatty acids and monoglycerides. The undigested triglycerides are excreted without being metabolized. As the undigested triglycerides are not absorbed, the resulting caloric deficit may have a positive effect on weight control. Clinical studies have shown that lipase inhibitors, taken prior to consuming a meal containing a moderate amount of fat, significantly increase the excretion of fat. In this fashion, a lipase inhibitor produces weight loss by blocking a percentage of fat that would normally be absorbed. Indeed, it has been shown that lipase inhibitors, such as the prescription drug tetrahydrolipstatin, generically known as Orlistat, are effective in obesity management. Cholecystokinin (CCK) is a peptide released following the consumption of food which is a major satiety signal in humans. Studies have shown that individuals receiving CCK demonstrate a reduction in caloric intake of from about 1622%. Although the full mechanism whereby CCK exerts its effect on satiety is not known, there appear to be two components, a central component involving CCK receptors in the brain and a peripheral component involving the stomach and small intestine. When food is consumed, CCK releasing protein (CCKRP) is released in the small intestine. CCKRP stimulates CCK release from intestinal cells. Web site: http://www.delphion.com/details?pn=US06558690__

Patents 181

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Percyquinnin, a process for its production and its use as a pharmaceutical Inventor(s): Hopmann; Cordula (Frankfurt am Main, DE), Kurz; Michael (Hofheim, DE), Mueller; Guenter (Sulzbach, DE), Toti; Luigi (Hochheim am Main, DE) Assignee(s): Aventis Pharma Deutschland GmbH (Frankfurt am Main, DE) Patent Number: 6,596,518 Date filed: April 6, 2001 Abstract: The present invention relates to a compound named Percyquinnin that is obtainable by cultivating a basidiomycetes Stereum complicatum (DSM 13303), and to its pharmaceutically acceptable salts. The present invention further relates to a process for the production of Percyquinnin and to the use of Percyquinnin and its pharmaceutically acceptable salts as pharmaceuticals, in particular to their use as inhibitors of lipase. Excerpt(s): This invention relates to a compound named Percyquinnin, its pharmaceutically acceptable salts and derivatives, and to methods for obtaining the compound. One method of obtaining the compound is by cultivation of the Basidiomycete Stereum complicatum, ST 001837 (DSM 13303). The present invention further relates to a process for the production of Percyquinnin, to the fungus ST 001837 (DSM 13303), to the use of Percyquinnin and its pharmaceutically acceptable salts and derivatives as pharmaceuticals, in particular to their use as lipase inhibitors, and to pharmaceutical compositions comprising Percyquinnin or a pharmaceutically acceptable salt or derivative thereof. Lipid metabolism normally keeps a delicate balance between synthesis and degradation. When the balance is upset, hyperlipidemia may occur, which in turn can cause atherosclerosis, hypertension, diabetes etc. Modulators of lipid metabolism may be expected to be useful in controlling these and other disorders. Inhibition of lipolysis in non-insulin-dependent diabetes mellitus (NIDDM) is supposed to reduce hyperglycemia. The initial event in the utilization of fat as an energy source is the hydrolysis of triacylglycerol by lipases, e.g., hormone sensitive lipase, and monoacylglycerol lipase. Hydrolyses of triacylglycerols may lead to increased levels of glycerol and fatty acids in the blood. Lipase inhibitors may be expected to reduce both plasma fatty acid levels and hyperglycemia with reduced side effects. Web site: http://www.delphion.com/details?pn=US06596518__

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Pharmaceutical composition and method for treatment of dyspepsia Inventor(s): Feinle; Christine (Adelaide, AU), Fried; Michael (Zurich, CH), Lengsfeld; Hans (Basel, CH), Rades; Thomas (Dunedin, NZ) Assignee(s): Hoffman-La Roche Inc. (Nutley, NJ) Patent Number: 6,534,539 Date filed: August 6, 2001 Abstract: The present invention relates to compositions containing lipase inhibitors, e.g. orlistat, and the use of such compositions for treating, reducing or preventing functional dyspepsiaafter ingestion of meals, especially of fat containing or fat rich meals. Excerpt(s): The present invention relates to compositions containing lipase inhibitors, e.g. orlistat, and the use of said compositions for treating, reducing or preventing functional dyspepsia after ingestion of meals, especially of fat containing or fat rich meals. Functional dyspepsia is a condition characterized by sensations of gastric

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fullness, nausea, bloating, gastric distress, etc., after intake of meals (even small meals), especially after intake of fat containing or fat rich meals. A large number of people are afflicted by this condition, continuously or more regularly in response to fat rich meals or fat rich meal items. The arrival of lipid in the small intestinal lumen normally causes gastric relaxation, modulation of phasic motor activity, and pancreaticobiliary secretion. However, in patients with functional dyspepsia, lipids often provoke postprandial symptoms. Gastric and pancreatic lipases in the intestinal lumen hydrolyze triglycerides to free fatty acids, which may act on brain centers involved in dyspeptic symptoms. Web site: http://www.delphion.com/details?pn=US06534539__ •

Plant lipases Inventor(s): Cahoon; Edgar B. (Wilmington, DE) Assignee(s): E. I. du Pont de Nemours and Company (Wilmington, DE) Patent Number: 6,673,988 Date filed: September 22, 2000 Abstract: This invention relates to an isolated nucleic acid fragment encoding a lipase. The invention also relates to the construction of a chimeric gene encoding all or a portion of the lipase, in sense or antisense orientation, wherein expression of the chimeric gene results in production of altered levels of the lipase in a transformed host cell. Excerpt(s): This invention is in the field of plant molecular biology. More specifically, this invention pertains to nucleic acid fragments encoding lipases in plants and seeds. True lipases act at an oil-water interface; they constitute a ubiquitous group of enzymes catalyzing a wide variety of reactions, many with industrial potential. Lipases have been grouped into families according to their amino acid sequence, enzymatic specificity, and differential expression. A family of lipolytic enzymes with members in Arabidopsis thaliana, rice and corn has been described (Brick et al. (1995) FEBS Lett. 377:475-480). It is possible to change the structure of fats and oils by manipulating the lipase specificity ending with products containing the desired fatty acid at a specific position on the glycerol backbone. Lipases play important roles in pathogen defense and in activating membrane formation. Web site: http://www.delphion.com/details?pn=US06673988__

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Polycondensation of organic silicon compounds Inventor(s): Friedrich; Thomas (Darmstadt, DE) Assignee(s): BASF Aktiengesellschaft (Ludwigshafen, DE) Patent Number: 6,617,411 Date filed: November 22, 2000 Abstract: A process is described for the polycondensation of organic silicon compounds at from pH 6 to 8 in the presence of a lipase which is, where appropriate, immobilized on a carrier composed of polymer materials. Suitable organic silicon compounds capable of polycondensation are (RO)(R.sup.1 O)(R.sup.2 O)(R.sup.3 O)Si, (RO)(R.sup.1 O)(R.sup.2 O)SiR.sup.3, (RO)(R.sup.1 O)Si (R.sup.2)(R.sup.3) and (RO) SiR.sup.1 R.sup.2 R.sup.3, where R, R.sup.1, R.sup.2 and R.sup.3 are independently of one another C.sub.1

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- to C.sub.10 -alkyl, C.sub.3 - to C.sub.10 -cycloalkyl, C.sub.4 - to C.sub.20 alkylcycloalkyl, aryl, C.sub.6 - to C.sub.16 -alkylaryl, the alkyl groups being linear or branched. It is advantageous and possible to obtain the lipase on a large scale relatively simply by fermentation processes. Preference is given to employing lipases from Pseudomonas species. Excerpt(s): The invention relates to a process for polycondensation of organic silicon compounds in the presence of an enzyme. Silicones and silicates are of industrial-scale importance. Silicates are employed, for example, as phase material in chromatography. There are numerous processes for their preparation. Processes leading to amorphous silicates, for example, start from orthosilicic acid which is condensed in aqueous solution with acid or base catalysis (A. F. Holleman, E. Wiberg, Lehrbuch der Anorganischen Chemie [Textbook of Inorganic Chemistry], Walter de Gruyter Verlag, Berlin N.Y. 1985, 91st-100th edition, pp. 757-764). Silicones can be prepared by condensation of silanols, silanediols and silanetriols (A. F. Holleman, E. Wiberg, Lehrbuch der Anorganischen Chemie, Walter de Gruyter Verlag, Berlin N.Y. 1983, 91st100th edition, pp.786-788). In novel processes developed in the last few years it is possible to condense organic silicon compounds under mild conditions. Enzymes are employed as catalysts. The reactions can be carried out at from pH 6 to pH 8. In 1998 a suitable enzyme has been isolated for the first time from a marine sponge, as described in J. N. Cha, K. Shimizu, Y. Zhou, S. C. Christiansen, B. F. Chmelka, G. D. Stucky, D. E. Morse, Proc. Natl. Acad. Sci. USA 1999, 96, 361-365. The enzyme is composed of three subunits, the so-called silicateins. Extracting the enzyme is relatively costly. Besides polycondensation in buffer solution, the organic silicon compounds (EtO).sub.4 Si and (EtO).sub.3 SiPh have been converted directly using air-dried enzyme. Moreover, WO 00/35993 describes employing synthetic homopolymers composed of cysteine and block polypeptides composed of lysine and cysteine for polycondensation of silicon alkoxides, metal alkoxides and derivatives thereof into silicates, polysiloxanes and polymetaloxanes. It is an object of the present invention to provide a further process for the polycondensation of organic silicon compounds, which can be carried out at from pH 6 to 8, and to find a suitable catalyst for this reaction. Web site: http://www.delphion.com/details?pn=US06617411__ •

Polypeptides having lipase activity and nucleic acids encoding same Inventor(s): Rey; Michael W. (Davis, CA), Golightly; Elizabeth J. (Davis, CA) Assignee(s): Novozymes Biotech, Inc. (Davis, CA) Patent Number: 6,686,189 Date filed: June 12, 2002 Excerpt(s): The present invention relates to isolated polypeptides having lipase activity and isolated nucleic acid sequences encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the nucleic acid sequences as well as methods for producing and using the polypeptides. Lipases (EC 3.1.1.3) are enzymes that can hydrolyze triglycerides to release fatty acid. Detergents formulated with lipolytic enzymes are known to have improved properties for removing fatty stains. For example, LIPOLASE.TM. (Novo Nordisk A/S, Bagsvaerd, Denmark), a microbial lipase obtained from the fungus Thermomyces lanuginosus (also called Humicola lanuginosa), has been introduced into many commercial brands of detergent.

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Web site: http://www.delphion.com/details?pn=US06686189__ •

Process for the manufacture of a vitamin E intermediate Inventor(s): Bonrath; Werner (Freiburg, DE), Eisenkraetzer; Detlef (Penzberg, DE), Enjolras; Valerie (St. Jean Bonnefonds, FR), Karge; Reinhard (Staufen, DE), Netscher; Thomas (Bad Krozingen, DE), Schneider; Michael (Frick, CH) Assignee(s): Roche Vitamins, Inc. (Parsippany, NJ) Patent Number: 6,743,615 Date filed: February 19, 2002 Abstract: The present invention is a process for converting trimethylhydroquinone diacetate (TMHQ-DA) into trimethylhydroquinone-1-monoacetate (TMHQ-1-MA) by contacting TMHQ-DA with a lipase to effect an enzymatic monosaponification of the TMHQ-DA. Also provided are methods of making (all-rac)-.alpha.-tocopherol and (allrac)-.alpha.-tocopherol acetate. Excerpt(s): The present invention relates to a process for converting trimethylhydroquinone diacetate (TMHQ-DA) into trimethylhydroquinone-1-monoacetate (TMHQ-1-MA) by contacting TMHQ-DA with a lipase to effect an enzymatic monosaponification of the TMHQ-DA. Methods of making (all-rac)-.alpha.-tocopherol and (all-rac)-.alpha.-tocopherol acetate are also provided. The major commercial form of vitamin E is its acetate derivative, synthesized by acetylation of (all-rac)-.alpha.tocopherol, e.g. with acetic anhydride. Industrial syntheses of (all-rac)-.alpha.tocopherol are based on the condensation of trimethylhydroquinone (TMHQ) with isophytol, phytol or a derivative thereof, such as a phytyl halide. TMHQ is normally obtained from 2,3,6-trimethylphenol which is expensive, however, and acidic catalysts have to be used for the condensation of the TMHQ with isophytol, phytol or a derivative thereof, such as a phytyl halide. Web site: http://www.delphion.com/details?pn=US06743615__

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Process for the preparation of acidic lipase Inventor(s): Bastawde; Kulbhushan Balwant (Pune, IN), Gokhale; Digambar Vitthal (Pune, IN), Khire; Jayant Malhar (Pune, IN), Mahadik; Nutan Dattatraya (Pune, IN), Puntambekar; Ulka Shrirang (Pune, IN) Assignee(s): Council of Scientific & Industrial Research (New Delhi, IN) Patent Number: 6,534,303 Date filed: March 13, 2001 Abstract: The present invention provides a process for the preparation of acidic lipase from microbial sources with activity at highly acidic pH, the process comprising growing Aspergillus niger sp. in a fermentation medium containing carbon and nitrogen sources along with nutrients, separating the fungal biomass and recovering the culture filtrate/broth and separating the lipase enzyme. Excerpt(s): The present invention relates to a process for the preparation of an acidic lipase. More particularly, the present invention relates to the production of thermostable and acid stable lipase using Aspergillus niger. Research on microbial lipases has increased in recent years because of their practical application in industry in

Patents 185

the hydrolysis of fats, production of fatty acids and food additives, synthesis of esters and peptides, resolution of racemic mixtures or as additives for detergents. [Bjorkling F., Godtfredsen S. E., and Kirk O., (1991), Trends Biotechnol. 9, 360-363]. These enzymes are widely distributed in filamentous fungi [Sugihara A., Shimada Y., and Tominaga Y., (1990), J. Biochem. 107, 426-430; Torossian K. and Bell A. W. (1991) Biotechnol. Appl. Biochem. 13, 205-211; Yadav R. P., Saxena R. K., Gupta R., and Davidson W. S., (1998) Biotechnol. Appl. Biochem. 28, 243-249], yeasts [Kalkote U. R., Joshi R. A., Ravindranathan T., Bastawade K. B., Patil S. G., and Gokhale D. V., (1992) Biotechnol. Lett. 14, 785-788; Valero F., Ayats F., Lopez-Santin J., and Poch M. (1998) Biotechnol. Lett. 10, 741-744; Dalmau E., Montesions J. L., Lotti M. and Casas C., (2000), Enzyme Microb. Technol. 26, 657-663] and bacteria [Jaeger K. E., Ransae S., Dijkstra B. W., Colson C., van Heuvel M. S. and Misset O. (1994) FEMS Microbiol. Rev. 15, 29-63; Jaeger K. E., Dijkstra B. W. and Reetz M. T., (1999) Ann. Rev. Microbiol. 53, 315-351]. Filamentous fungi are preferred sources of lipase since they secrete the enzymes extracellularly. The most productive strains known till date belong to the genera Rhizopus, Mucor, Geotrichum, Penicillium and Aspergillus [Bjorkling F., Godtfredsen S. E., and Kirk O., (1991), Trends Biotechnol. 9, 360-363]. An acid resistant lipase preparation active between pH 4.5-5.5 was reported from Aspergillus niger [Torossian K. and Bell A. W. (1991) Biotechnol. Appl. Biochem. 13, 205-211]. Lipases active at highly acidic pH's have not been reported so far from microbial sources. Such acidic lipases have potential applications in the food industry. It is therefore desirable to obtain such acidic lipases which are active at highly acidic pH from microbial sources. Web site: http://www.delphion.com/details?pn=US06534303__ •

Processes for synthesis and purification of nondigestible fats Inventor(s): Howie; John Keeney (Oregonia, OH), Trout; James Earl (West Chester, OH) Assignee(s): The Procter & Gamble Co. (Cincinnati, OH) Patent Number: 6,566,124 Date filed: September 15, 2000 Abstract: A process for removing digestible fat from a crude reaction mixture comprising nondigestible fat and at least one digestible fat selected from the group consisting of digestible fats having fatty acid chains, comprising the steps of: (1) treating the crude reaction mixture with an aqueous solution comprising lipase at a pH sufficient to obtain soaps from the fatty acid chains; and (2) removing the soaps. Excerpt(s): This patent application cross-references and incorporates by reference copending patent application "Synthesis of Higher Polyol Fatt) Acid Polyesters by Transesterification", filed in the name of Trout et al. and co-pending application "Improved Processes for Synthesis and Purification of Nondigestible Fats Using Lipase", filed in the name of Trout et al., both applications filed on the same date as this application. This invention relates to low-temperature atmospheric pressure processes for the purification of polyol fatty acid polyesters or other nondigestible fats that have a digestible fat, such as a triglyceride, in the final product. More particularly, this invention relates to processes for purifying nondigestible fats from a crude reaction mixture by use of an aqueous solution comprising lipase. The food industry has recently focused attention on polyol fatty acid polyesters for use as low-calorie fats in food products. Triglycerides (triacylglycerols) constitute about 90% of the total fat consumed in the average diet. One method by which the caloric value of edible fat could be lowered would be to decrease the amount of triglycerides that is absorbed in the human

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system, since the usual edible triglyceride fats are almost completely absorbed (see Lipids, 2, H. J. Deuel, Interscience Publishers, Inc., New York, 1955, page 215). Low calorie fats which can replace triglycerides are described in Mattson, et al., U.S. Pat. No. 3,600,186. Mattson, et al. disclose low calorie, fat-containing food composition in which at least a portion of the triglyceride content is replaced with a polyol fatty acid ester having at least four fatty acid ester groups, with each fatty acid having from eight to twenty-two carbon atoms. Web site: http://www.delphion.com/details?pn=US06566124__ •

Product for topical application containing a lipase and a hydroxy acid precursor Inventor(s): Guth; Gerard (Montmorency, FR), Maurin; Emmanuelle (L'Isle-Adam, FR), Sera; Daniel (L'Hay les Roses, FR) Assignee(s): L'Oreal (Paris, FR) Patent Number: 6,488,928 Date filed: October 24, 1995 Abstract: The present invention concerns a product for topical application, capable of releasing a hydroxy acid on the skin, containing a lipase as enzyme and at least one precursor of the hydroxy acid. The precursor is an ester of the hydroxy acid, containing at least one ester functional group having a saturated or unsaturated, linear or branched chain and from 2 to 25 carbon atoms. According to a preferred form, the precursor and the lipase are packaged so as not to be in contact with one another until the time of application to the skin. Excerpt(s): The present invention concerns a product for topical application which is capable of releasing a hydroxy acid on the skin, and the use thereof in imparting softness to the skin, including the scalp. The present invention also concerns a process for the cosmetic and/or dermatological treatment of the skin, particularly for the treatment of acne, wrinkles and fine lines, and the use of the present product therein. Hydroxy acids are increasingly used in the cosmetics or dermatological fields for caring for the face and/or the body, and more especially, for giving the face a luminous and radiant complexion, and therefore a healthy, smooth and younger appearance, and for causing the disappearance of blackheads due to acne. Unfortunately, hydroxy acid compounds are generally provided in compositions having a pH of less than or equal to 4, for the purpose of maintaining the activity of these acids. The application of these compositions to the skin has the major disadvantage of causing stinging, itching and stabbing pains, which can produce great discomfort. The use of these acidic compositions for users with sensitive skin is therefore often out of the question. Web site: http://www.delphion.com/details?pn=US06488928__

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Solid detergents with active enzymes and bleach Inventor(s): Scepanski; William H. (Bloomington, MN) Assignee(s): Sunburst Chemicals, Inc. (Bloomington, MN) Patent Number: 6,777,383 Date filed: March 27, 2002

Patents 187

Abstract: A detergent composition is described which is a solid homogeneous, evenly dispersed composition containing anionic and nonionic surfactants, soil suspending agents, chelating or sequestering agents, and alkaline builders. The detergent compositions will contain either active enzymes, an oxygen releasing bleaching agent or both. The active enzymes can be protease, amylase or lipase enzymes. Said composition can be used for laundry washing or hard surface cleaning. Manufacturing procedures and methods of use are described. Excerpt(s): The invention relates to solid detergents. The invention relates more specifically to solid detergents having enzymes and stable oxygen-releasing bleaching agents that are stable upon storage of the detergent. Detergent systems for laundry, warewashing, hard surface cleaning (food plant, institutional, industrial, transportation), and numerous other similar applications have long been available where powders are manually scooped into water and dissolved. The resulting detergent solution is applied to the surface or article being cleaned. Also, concentrated liquid detergents have been found to be highly desirable by certain consumers. Important considerations in the selection of a detergent composition include ease of handling, cleaning ability and stability of the product during storage. The basic ingredients of a detergent are surfactants, which emulsify and suspend soils, and alkaline builders, which saponify fats and oils. One advantage of powder detergents is the high concentrations of active ingredients because few or no inert ingredients are required. In powder detergents, high levels of inorganic or organic salts can be used to raise alkalinity and soften water by chelating or sequestering water hardness ions. The powdered detergents can be used to provide oxidizing agents (bleaches) or reducing agents (for example, sodium thiosulfate) and granular enzyme materials, which can be blended into free flowing powder detergents. The oxidizing or reducing agents and the enzymes are stable in the powdered detergents with no significant loss of activity on extended storage. Web site: http://www.delphion.com/details?pn=US06777383__ •

Stabilized rice bran deer feed, attractant and browse supplement Inventor(s): Chastain; Jason N. (Stuttgart, AR) Assignee(s): Producers Rice Mill, Inc. (Stuttgart, AR) Patent Number: 6,616,924 Date filed: June 2, 2000 Abstract: Deer attractant and feed comprising stabilized rice bran and calcium carbonate is disclosed. Limestone is added to the rice during the milling process. The residue from this process, rice bran and a small amount of pulverized limestone, is the cooked in an extruder, resulting in stabilized rice bran. The extrusion process destroys lipase activity and reduces the free fatty acid content to under 4%. The product contains about 12.5% or more protein, and preferably has a 2:1 ratio of calcium to phosphorous. Because of the balanced nutritional analysis and the addition of calcium carbonate to the feed, the product aids in promoting overall deer growth as well as bone growth in bucks. The product also acts as a deer attractant, moving deer toward sources of adequate food supplies and away from cultivated gardens and crops. Excerpt(s): Traditional deer feeds and attractants, such as corn and salt, are not optimal for deer's health. Regulations have been enacted, such as those adopted by the Texas A&M Animal Health Divisions, concerning the use of feed grains contaminated by

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aflatoxins. Needs exist for deer feeds and attractants that are beneficial to deer and herds. The present invention is for deer attractant and feed comprising mostly of stabilized rice bran. Web site: http://www.delphion.com/details?pn=US06616924__ •

Synthesis of B-keto esters Inventor(s): Cordova; Armando (La Jolla, CA), Janda; Kim D. (La Jolla, CA) Assignee(s): The Scripps Research Institute (La Jolla, CA) Patent Number: 6,642,035 Date filed: January 26, 2001 Abstract:.beta.-keto esters are prepared by way of a lipase-catalyzed transesterification. The synthetic methodology provides a simple scheme for the synthesis of optically active.beta.-keto esters that are useful building blocks and starting materials for natural product synthesis. Moreover, the methodology employs mild, solvent-free conditions. The methodology may also be employed for resolving racemic alcohols. Excerpt(s): The invention relates to the synthesis of.beta.-keto esters. More particularly, the invention relates to a highly chemo- and stereoselective synthesis of.beta.-keto esters via a polymer-supported lipase catalyzed transesterfication.beta.-keto esters are noteworthy in that they represent an important class of organic building blocks used in the synthesis of complex natural products (S. Benetti, et al., Chem Rev. 1995, 95, 1065). A seemingly straight-forward method to prepare these molecules is through an alcohol based transesterification (J. G. Gilbert, et al., J. Org. Chem. 1988, 53, 449; D. F. Taber, et al., J. Org. Chem. 1985, 50, 3618). Yet the synthesis of allylic and propargylic.beta.-keto esters is not trivial by this route due to their acid/base lability and sigmatropic rearrangement of the.beta.-keto ester. To circumvent these problems a report has appeared describing the heating of alcohols with.beta.-keto esters in toluene (C. Mottet, et al., J. Org. Chem. 1999, 64, 138;). However, the reaction times were lengthy and yields variable for many of the substrates. Another mild method uses crystalline microporous nanosilicates (zeolites) as the catalyst for the transesterification in refluxing toluene to avoid potential side reactions, but here the yields were even lower compared to the former case (B. S. Balaji, et al., J. Chem. Soc. Chem. Commun. 1996, 707). Furthermore, none of these or any of the conventional methods display stereoselectivity or chemoselectivity between aliphatic alcohols or phenols. What is required is a general method of synthesizing.beta.-ketoesters either as racemates or as single enantiomers. What is required is a general method for resolving alcohol racemates. Candida antarctica lipase B (CALB) immobilized on a macroporous poly(propylene) resin (Novozym 435) catalyzed the transesterification of.beta.-keto esters under environmentally safe conditions. The reactions were performed by simply solubilizing the alcohols in methyl or ethyl.beta.-keto esters and then treating the reaction mixture with the lipase under reduced pressure. The.beta.-keto ester products were obtained in high yields (>90%) and CALB was chemoselective in the acylation of aliphatic alcohols in the presence of phenols. In addition, CALB was able to resolve sec-alcohols with high enantioselectivity. This is a general route to prepare.beta.-keto esters by lipase-catalyzed transesterification and it can be of ample use due to its mild, solvent-free conditions. Moreover, it also provides a simple protocol to produce optically active.beta.-keto esters that are useful building blocks and starting materials for natural product synthesis. Web site: http://www.delphion.com/details?pn=US06642035__

Patents 189

Patent Applications on Lipase As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to lipase: •

Alkaline lipase from Vibrio metschnikovii RH530 N-4-8 and nucleotide sequence encoding the same Inventor(s): Jhon, Sung Hoo; (Seoul, KR), Jin, Ghee Hong; (Seoul, KR), Lee, Hyun Hwan; (Yongin-City, KR), Rho, Hyune Mo; (Seoul, KR) Correspondence: Cantor Colburn Llp; 55 Griffin South Road; Bloomfield; CT; 06002; US Patent Application Number: 20040009570 Date filed: June 24, 2003 Abstract: An alkaline lipase isolated from Vibrio metschnikovii RH530 and a polynucleotide sequence encoding the same are provided. The isolated alkaline lipase has an amino acid sequence of SEQ ID NO: 5 and the polynucleotide having a base sequence of SEQ ID NO: 4 encodes the alkaline lipase. The isolated alkaline lipase exhibits an optimal activity at a high pH level, that is, at pH 10.about.11, and has very high ratio of residual enzyme activity and high compatibility with a surfactant, so that it can be suitably used as an enzyme for a laundry detergent. Excerpt(s): This application claims priority from Korean Patent Application No. 200235410, filed on Jun. 24, 2002, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein in its entirety by reference. The present invention relates to an alkaline lipase isolated from Vibrio metschnikovii RH530 N-4-8 and a gene encoding the same. The present invention also relates to a recombinant vector containing the gene, a transformed host cell transformed with the recombinant vector and a method of producing an alkaline lipase using the transformed host cell. An alkaline lipase hydrolyses triacylglycerol into glycerol and fatty acid at alkaline pH. Various microorganisms producing an alkaline lipase have been reported. Specifically, representative examples of such microorganisms include Pseudomonas, and Bacillus. These enzymes have been applied to industrial fields of detergents that necessitate hydrolysis of lipids under alkaline conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Anti-obesity compositions Inventor(s): Bailly, Jacques; (Rixheim, FR), Martin, Rainer Eugen; (Grenzach-Wyhlen, DE), Raab, Susanne; (Leinfelden-Echterdingen, DE) Correspondence: Hoffmann-La Roche INC.; Patent Law Department; 340 Kingsland Street; Nutley; NJ; 07110 Patent Application Number: 20040033983 Date filed: April 23, 2003 Abstract: The present invention relates to compositions and methods for treating obesity. More particularly, the invention relates to a composition comprising a lipase

9

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

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inhibitor such as orlistat, and glucomannan such as konjac as well as methods for utilizing such compositions and kits for carrying out this method. Excerpt(s): The field of this invention is the field of combating obesity utilizing compositions containing lipase inhibitors. Adverse effects which occasionally are observed in patients treated with lipase inhibitors are anal leakage of oil (oily spotting) and fecal incontinence. Oily spotting results from physical separation of some of the ingested but unabsorbed dietary fat from the bulk of the fecal mass in the colon. In U.S. Pat. No. 5,447,953 it has been shown that by combining a lipase inhibitor with substantial amounts of water insoluble crude fibers, the inhibiting effect on fat absorption can be increased. International Patent Application WO 00/09123 demonstrates that by combining a lipase inhibitor such as orlistat with low amounts of chitosan or a derivative or a salt thereof, the phenomenon of anal leakage of oil can be strongly reduced. Various approaches to control oily leakage have been discussed. Among such strategies are i) use of a surfactant to stabilize the oil/water interface in order to prevent coalescence of the oil emulsion in the colon, ii) enhancing water viscosity in the colon to reduce both intensity and frequency of droplet-droplet interactions and by that reducing the probability of coalescence, iii) physical absorption of oil by a lipophilic compound, or iv) increasing the natural stool mass by facilitating bacterial growth in the colon. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Biotin-peg-substrate for a lipase assay Inventor(s): Fowler, Anne; (Forest Farm Estate, GB), Hawes, Calvin Richard; (Forest Farm Estate, GB), James, David Martin; (Forest Farm Estate, GB), Poulsen, Fritz; (Bagsvaerd, DK), Price-Jones, Molly Jean; (Forest Farm Estate, GB), Tornqvist, Hans; (Bagsvaerd, DK) Correspondence: Amersham Biosciences; Patent Department; 800 Centennial Avenue; Piscataway; NJ; 08855; US Patent Application Number: 20040014133 Date filed: December 9, 2002 Abstract: Disclosed is a compound of Formula (I), wherein: L is a linking agent; B is a binding agent; X is an atom or group suitable for attaching L to the glycerol chain; and R is a straight chain saturated or unsaturated alkyl group having from 8 to 30 carbon atoms, substituted with M' or M" wherein at least one of M' and/or M" is a detectable label. The compound can be used as a lipase substrate in a solid phase-based assay system, such as a scintillation proximity assay, to detect lipase enzyme activity. Excerpt(s): The present invention describes a novel substrate for use in an assay for lipase enzyme activity. In particular, this novel substrate can be labelled and used in a homogeneous assay. Lipases are enzymes that catalyse the hydrolysis of triacylglycerols in the first step in recovering stored fatty acids for energy production. The sequence of hydrolysis from the three positions on glycerol depends on the specificity of the particular lipase involved. Lipase enzyme activity is an important function and its strict regulation is necessary to ensure healthy metabolism. For example, lipases in adipose tissue are key enzymes for the release of major energy stores. Their activity is under hormonal control to ensure that triacylglycerol hydrolysis is balanced with the process of triacyglycerol synthesis to assure adequate energy stores and yet avoid levels of fatty acids becoming so high as to cause adverse effects.

Patents 191

Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Carotene-specific lipase Inventor(s): Berger, Ralf G.; (Hannover, DE), Takenberg, Meike; (Garbsen, DE), Zorn, Holger; (Seelze, DE) 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: 20040147005 Date filed: September 5, 2003 Abstract: Enzymes active in the hydrolysis of carotenoid esters have been obtained from Pleurotus sapidus. A particularly active enzyme has been identified having an isoelectric point of about 5.7 and a molecular weight of about 101 kDA. A method of preparing carotenoid compounds from their respective esters comprises contacting the ester with the aforementioned enzyme. Carotene--comprising stains can be treated by the aforementioned enzyme, preferably followed by treatment with a conventional detergent or an enzyme active in cleaving carotenoids. A detergent comprising the aforementioned enzymes is also provided. Excerpt(s): This application claims priority under 35 U.S.C.sctn. 119(a) to European Application Serial No. 02447169.0, filed Sep. 6, 2002 (Attorney Docket No. CM2697F). This invention relates to a carotene-specific lipase enzyme, detergent compositions comprising the lipase enzyme and methods for degrading carotenoid esters and methods for treating carotene-comprising stains. Carotenoid substances are widely used as colorants and additives in food and animal feed as well as cosmetics. Carotenoids are found in many fruit and vegetables such as peppers, marigold, tomatoes etc. Most of the naturally occurring carotenoid substances are present as esters of fatty acids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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DNA encoding a plant lipase, transgenic plants and a method for controlling senescence in plants Inventor(s): Hong, Yuwen; (Waterloo, CA), Hudak, Katalin; (East Brunswick, NJ), Thompson, John E.; (Waterloo, CA), Wang, Tzann-Wei; (Waterloo, CA) Correspondence: Kenyon & Kenyon; 1500 K Street, N.W., Suite 700; Washington; DC; 20005; US Patent Application Number: 20040158891 Date filed: October 1, 2003 Abstract: Regulation of expression of senescence in plants is achieved by integration of a gene or gene fragment encoding senescence-induced lipase into the plant genome in antisense orientation. The carnation and Arabidopsis genes encoding senescenceinduced lipase are identified and the nucleotide sequences are used to modify senescence in transgenic plants. Excerpt(s): This application is a continuation-in-part of application Ser. No. 09/597,774, which is a continuation-in-part application of application Ser. No. 09/250,280 which is a continuation-in-part application of application Ser. No. 09/105,812, filed Jun. 26, 1998,

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and incorporated herein in its entirety by reference thereto. The present invention relates to polynucleotides which encode plant polypeptides and which exhibit senescence-induced expression, transgenic plants containing the polynucleotides in antisense orientation and methods for controlling senescence in plants. More particularly, the present invention relates to plant lipase genes whose expression is induced by the onset of senescence and the use of the lipase gene to control senescence in plants. Senescence is the terminal phase of biological development in the life of a plant. It presages death and occurs at various levels of biological organization including the whole plant, organs, flowers and fruit, tissues and individual cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Drugs and foods improving the quality of life and process for producing the same Inventor(s): Ando, Kunio; (Kanagawa, JP), Fukuda, Akio; (Tokyo, JP), Igusa, Kazuo; (Shizuoka, JP), Kawai, Juri; (Tokyo, JP), Ogasawara, Toshichika; (Shizuoka, JP), Suzuki, Seikichi; (Kanagawa, JP) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20040018190 Date filed: May 23, 2003 Abstract: The present invention relates to drugs and foods produced by applying a method whereby a biological activity can be efficiently exerted in the case of orally administering a biologically active protein.The oral composition according to the present invention contains at least one biologically active protein as the active ingredient and has a means of controlling the release. According to the composition of the present invention, at least 10% of the active ingredient is delivered to the lower digestive tract while sustaining its activity. Namely, the biologically active protein is not degraded in the stomach but delivered to the small intestine, which makes it possible to ensure the exertion of its drug's effect exert a hitherto unknown effect. It is preferable that the biologically benefical active protein contained in the composition according to the present invention is lactoferrin, immunoglobulin, lysozyme, an amylase, a protease, a lipase or a digestive enzyme inhibitor. Excerpt(s): This invention relates to drugs and foods produced by applying a method whereby a biological activity can be efficiently exerted in the case of a biologically active protein is orally administered. Namely, the present invention relates to drugs and foods wherein orally administered biologically active proteins passe through the stomach without being activated and reach the digestive tract lower than the duodenum (i.e., the action site) while sustaining its biological activity. Further, the present invention relates to diseases which can be newly treated/prevented by these drugs or foods. The method according to the present invention, wherein a biologically active protein can be delivered to the action site without being degraded, is highly efficacious for exerting biological properties. The small intestinal mucosa, which controls the digestion and absorption of foods, has fine villi covering its surface and the villi are further coated with smaller villi. Owing to this structure, the surface area of the mucosa is extremely enlarged. According to one estimate, the surface area of the human digestive tract Is 1.5 times larger than a tennis court and the small intestine accounts for major part. It is said that 150 trillion enteric gastrointestinal microflora inhabit the inner cavity of the gastrointestinal tract which can be regarded as outside of the living body. Namely, the human body is in contact with the outside over such a large area and nothing but a thin

Patents 193

mucous layer is provided as a partition wall between the body and the outside. This thin mucous layer seemingly responds to various external stimulations. However, it is almost unclear how the mucosa responds to a stimulus coming into contact with it, which part of the mucosa accepts a stimulation, and so on. That is to say, the stimulation-response mechanism of the mucosa still remains unknown. Anyway, it is true that the digestive tract mucosa plays an extremely important role In vivo. As a good example of the response of the intestinal mucosa to a stimulation, the function of the mucosa as a barrier against the invasion of intestinal microflora may be cited. That is to say, intestinal microflora would scarcely invade beyond the barrier so long as an animal is in good health. Once an animal suffers stress due to a surgical operation, trauma, burn, etc. or dies, the intestinal microflora immediately begin to invade into its body beyond the mucous layer. In the normal state, it is therefore supposed that some protection mechanism operates to prevent the intestinal microflora continuously trying to invade. In addition to the intestinal microflora, it is considered that the intestinal mucosa is stimulated by viruses, toxins present in foods and so on. Although it is considered that the intestinal mucosa having such a large area should carry some sensors receiving stimulation and reactors reacting when the sensors receive stimuli, it is scarcely known what kinds of sensors operate therein. For example, it has been clarified that a lactoferrin receptor exists In the intestinal mucosa, However, it has never been known how lactoferrin reacts after binding to the receptor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Enzymatic modification of sterols using sterol-specific lipase Inventor(s): Basheer, Sobhi; (Sachnin, IL), Plat, Dorit; (Adi, IL) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20040105931 Date filed: June 5, 2003 Abstract: The invention relates to a process for the selective alcoholysis of a free sterol, by contacting said free sterol with a fat-based product, optionally with the addition of carboxylic fatty acid(s) and/or ester derivative(s) thereof that are not derived from said fat-based product, in the presence of an immobilized lipase complex which may optionally be surfactant-coated, which complex possesses a high level of sterol-specific alcoholytic and/or esterfication activity and minimal acidolytic and transesterification activities. The fat-based product is a nutritional product or food, particularly butterfat, or a cosmetic or cosmetic or cosmetic-related product. The process may be used for preparing substantially cholesterol-free fat-based products, particularly products containing butterfat, by selectively esterfying any free cholesterol contained therein by the immobilized, preferably surfactant coated lipase. The invention also relates to a process for the in situ enrichment of a fat-based product with esterified phytosterol ester(s). In this process, the esterification of the phytosterol is simultaneously accompanied by esterification of any free cholesterol present in said fat-based product. Excerpt(s): The present invention is concerned with the use of lipases for the selective alcoholysis and/or esterification of sterols. More specifically, the invention relates to the use of lipases for the selective alcoholysis and/or esterification of free cholesterol in foods, particularly in butterfat. The present invention further relates to a process for in situ enriching a fat-based product with esterified phytosterol ester(s) and simultaneously depleting the free cholesterol content of said fat-based product. Sterols

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are alcohols containing a steroid nucleus linked to an 8 to 10-carbon side-chain and a hydroxy group. Such compounds have a wide distribution in the plant and animal kingdoms. The most prevalent plant sterol is ergosterol, while the animal sterol of greatest significance is cholesterol. In recent years it has been increasingly recognized that certain lipid components present in food, including cholesterol, constitute significant risk factors in the pathogenesis of atherosclerotic disease. As a result of research in this field, there have been many attempts to develop methods for modifying the composition of many widely consumed food products, such that the levels of potentially harmful lipid and lipid-like substances are reduced. Of particular prominence in this field are those studies directed at reducing the cholesterol content of food products. In this regard, there is a general interest in developing methods of modifying important dietary fats, such as butterfat, for use in the preparation of low- or zero-cholesterol containing foodstuffs such as butter and ice cream. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Enzymatic resolution of aryl and thio-substituted acids Inventor(s): Skonezny, Paul M.; (Cicero, NY), White, Brenda J.; (Jamesville, NY), You, Li; (Jamesville, NY), Zha, Shannon X.; (East Syracuse, NY), Zhu, Jingyang; (Jamesville, NY) Correspondence: Stephen B. Davis; Bristol-Myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20040072310 Date filed: July 23, 2003 Abstract: Provided is a method of resolving a racemic mixture of a compound of formula I to obtain a desired enantiomer: 1wherein Ar is C.sub.6 or C.sub.10 aromatic group that can be substituted with H, C.sub.1 to C.sub.6 alkyl, trifluoromethyl or halo, R.sub.5 is halo or --S--R.sub.1, wherein R.sub.1 is H or acetyl, and R.sub.2 is H or C.sub.1 to C.sub.6 alkyl, the method comprising: reacting a compound of formula I wherein the compound is an ester whereby R.sub.2 is C.sub.1 to C.sub.6 alkyl with a lipase derived from Mucor meihei to stereoselectively hydrolyze the ester bond to produce an acid; and isolating the acid, wherein the reaction is conducted in a solvent comprising 80% to 98% v/v % organic phase and a residue of water phase (which can be buffered). Excerpt(s): This application claims priority from U.S. Application No. 60/233,193 filed Sep. 15, 2000. Over the last several years compounds have been reported in the patent and technical literature as possessing angiotensin converting enzyme (ACE) inhibitory activity or neutral endopeptidase (EC 3.4.24.11; NEP) inhibitory activity. Additional compounds have been identified that possess both inhibitory activities. These dual inhibitor compounds are of interest as cardiovascular agents particularly in the treatment of hypertension, congestive heart failure, and renal disease. These compounds are also referred to as vasopeptidase, dual metalloprotease, NEP/ACE, or ACE/NEP inhibitors. Omapatrilat, its preparation, and its use in treating cardiovascular disease are disclosed by Robl in U.S. Pat. No. 5,508,272. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Enzymes cooated with ionic liquid Inventor(s): Kim, Mahn-Joo; (Pohang-city, KR), Lee, Jae Kwan; (Suwon-city, KR) Correspondence: Baker & Botts; 30 Rockefeller Plaza; New York; NY; 10112 Patent Application Number: 20040087462 Date filed: September 10, 2003 Abstract: Disclosed is an ionic liquid-coated enzyme, wherein the ionic liquid is an organic salt which presents as a liquid phase at a temperature of about 150.degree. C. or below. The ionic liquid-coated enzyme according to the present invention remarkbly improves enzyme functions, such as enantioselectivity and stability, when the enzyme which may be lipase is coated with an ionic liquid. Further, even in the case of when the ionic liquid-coated enzyme is reused, the enantiomeric excess, enantioselectivity, and activity are not degenerated. The coated enzyme is usable as a catalyst for providing a chiral intermediate required in the synthesis of chiral pesticides, medicines, natural chemicals, and so on. Excerpt(s): The present Invention relates to an enzyme coated with an Ionic liquid and more particularly, to the preparation and use of an enzyme coated with an ionic liquid, which shows better enantioselectivity than its uncoated counterpart and can be repeatedly reused with no significant loss in catalytic activities. Enzymatic kinetic resolution of racemic substrates using hydrolytic enzymes provides a useful methodology for the preparation of optically active compounds. Among the hydrolytic enzymes, lipases (lipid-hydrolyzing enzymes) are of great use since they show broad substrate specificity. Lipases are particularly useful in the resolution of racemic alcohols and their esters In organic solvents. However, they often exhibit unsatisfactory enantioselectivity, resulting in a poor resolution. Accordingly, It is highly important to develop new methods for enhancing the lipase enantioselectivity. Various techniques have been so far developed for solving the enantioselectivity problem, A representative approach is the coating of enzyme with a lipid (Okahata, Y.; Hatano, A.; Ijiro, K Tetrahedron: Asymmetry 1995, 6, 1311) or a surfactant (Huang, S. Y.; Chang, H. L; Goto, M. Enzyme Microb. Technol., 1998, 22, 552). However, these methods are rather complicated to follow and cause loss in enzyme activities. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Feline pancreatic lipase composition and method of preparing and using such composition Inventor(s): Steiner, Jorg M.; (College Station, TX), Williams, David A.; (College Station, TX) Correspondence: Bracewell & Patterson, L.L.P.; Attention: J. Wendy Davis, PH.D.; P.O. Box 61389; Houston; TX; 77208-1389; US Patent Application Number: 20030207333 Date filed: May 2, 2003 Abstract: A novel form of lipase, namely feline pancreatic lipase (also termed feline classical pancreatic lipase) has an N-terminal amino acid sequence as shown in SEQ ID NO. 1. A method of purifying this lipase includes collecting pancreatic tissue from cats, delipidating the pancreatic tissue to produce a delipidated pancreatic extract, extracting pancreatic lipase from the delipidated pancreatic extract, and eluting the extracted

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pancreatic lipase through various columns. This lipase can be used for measuring pancreatic lipase immunoreactivity in serum thereby diagnosing pancreatitis in cats. To do so, antiserum against feline pancreatic lipase is prepared, and immunoassays are then performed in serum samples using this antiserum. In the event that increased concentration of pancreatic lipase immunoreactivity above the control range is detected in the serum, the cat might have pancreatitis. Excerpt(s): This nonprovisional application claims priority of U.S. Provisional Patent Application Serial No. 60/377,522, filed on May 3, 2002. The present invention relates generally to the field of biology and medicine. More particularly, the present invention relates to feline pancreatic lipase compositions, methods for preparing such compositions, and methods for employing such compositions to detect the concentration of pancreatic lipase in cat serum for diagnosis and management of pancreatitis. Lipases are water-soluble enzymes that hydrolyze water-insoluble substrates into more polar lipolysis products (Petersen and Drabl.o slashed.s, 1994). In 1856 Claude Bernard identified the first lipase (Petersen and Drabl.o slashed.s, 1994). Since then a plethora of lipases has been identified in microorganisms, plants, and animals (Lin et al., 1986; Jaeger et al., 1994; Petersen and Drabl.o slashed.s, 1994; Mukherjee and Hills, 1994; Lawson et al., 1994). Lipases share a common triad of amino acids (serine, aspartic or glutamic acid, and histidine) in the active site, which is also shared with serine proteases (Svendsen, 1994). Another common feature of almost all lipases are glycosylation site motifs (Antonian, 1988). Many lipases have been shown to be related phylogenetically. The pancreatic lipase gene family is a large gene family with 9 subfamilies (Petersen and Drabl.o slashed.s, 1994; Carrire et al., 1997; Carrire et al., 1998; Hirata et al., 1999). In addition there are other groups of phylogenetically related lipases, and yet other lipases that do not belong to a defined gene family (Anderson and Sando, 1991). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Isolated human lipase proteins, nucleic acid molecules encoding human lipase proteins, and uses thereof Inventor(s): Beasley, Ellen M.; (Darnestown, MD), Di Francesco, Valentina; (Rockville, MD), Yan, Chunhua; (Boyds, MD) Correspondence: Celera Genomics CORP.; Attn: Wayne Montgomery, Vice Pres, Intel Property; 45 West Gude Drive; C2-4#20; Rockville; MD; 20850; US Patent Application Number: 20040121441 Date filed: September 2, 2003 Abstract: The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the lipase peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the lipase peptides, and methods of identifying modulators of the lipase peptides. Excerpt(s): The present invention is in the field of lipase proteins that are related to the lysosomal acid lipase subfamily, recombinant DNA molecules, and protein production. The present invention specifically provides novel peptides and proteins that effect protein phosphorylation and nucleic acid molecules encoding such peptide and protein molecules, all of which are useful in the development of human therapeutics and diagnostic compositions and methods. The lipases comprise a family of enzymes with the capacity to catalyze hydrolysis of compounds including phospholipids, mono-, di-,

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and triglycerides, and acyl-coa thioesters. Lipases play important roles in lipid digestion and metabolism. Different lipases are distinguished by their substrate specificity, tissue distribution and subcellular localization. Lipases have an important role in digestion. Triglycerides make up the predominant type of lipid in the human diet. Prior to absorption in the small intestine, triglycerides are broken down to monoglycerides and free fatty acids to allow solubilization and emulsification before micelle formation in conjunction with bile acids and phospholipids secreted by the liver. Secreted lipases that act within the lumen include lingual, gastric and pancreatic lipases, each having the ability to act under appropriate pH conditions. Modulating the activity of these enzymes has the potential to alter the processing and absorption of dietary fats. This may be important in the treatment of obesity or malabsorption syndromes such as those that occur in the presence of pancreatic insufficiency. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Lipase variants Inventor(s): Borch, Kim; (Birkerod, DK), Glad, Sanne O. Schroder; (Ballerup, DK), Munk, Signe; (Kobenhavn K, DK), Patkar, Shamkant Anant; (Lyngby, DK), Svendsen, Allan; (Horsholm, DK), Vind, Jesper; (Vaerlose, DK) Correspondence: Novozymes North America, INC.; 500 Fifth Avenue; Suite 1600; New York; NY; 10110; US Patent Application Number: 20040053360 Date filed: July 3, 2003 Abstract: Attaching a peptide extension to the C-terminal amino acid of a lipase reduces the tendency to form odor. This may lead to lipase variants with a reduced odor generation when washing textile soiled with fat which includes relatively short-chain fatty acyl groups (e.g. up to C8) such as dairy stains containing butter fat or tropical oils such as coconut oil or palm kernel oil. Excerpt(s): The present invention relates to lipase variants with reduced potential for odor generation and to a method of preparing them. It particularly relates to variants suited for use in detergent compositions, more particularly variants of the Thermomyces lanuginosus lipase showing a first-wash effect and a reduced tendency to form odors when washing cloth soiled with milk fat. Lipases are useful, e.g., as detergent enzymes to remove lipid or fatty stains from clothes and other textiles, as additives to dough for bread and other baked products. Thus, a lipase derived from Thermomyces lanuginosus (synonym Humicola lanuginosa, EP 258 068 and EP 305 216) is sold for detergent use under the tradename Lipolase.RTM. (product of Novo Nordisk A/S). WO 0060063 describes variants of the T. lanuginosus lipase with a particularly good first-wash performance in a detergent solution. WO 9704079, WO 9707202 and WO 0032758 also disclose variants of the T. lanuginosus lipase. In some applications, it is of interest to minimize the formation of odor-generating short-chain fatty acids. Thus, it is known that laundry detergents with lipases may sometimes leave residual odors attached to cloth soiled with milk (EP 430315). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Lipolytic enzyme genes Inventor(s): Patkar, Shamkant Anant; (Lyngby, DE), Tsutsumi, Noriko; (Ichikawa-shi Chiba-ken, JP), Vind, Jesper; (Vaerlose, DE) Correspondence: Novozymes North America, INC.; 500 Fifth Avenue; Suite 1600; New York; NY; 10110; US Patent Application Number: 20040101928 Date filed: July 2, 2003 Abstract: The inventors have isolated novel genes with a high homology to the T. lanuginosus lipase gene and are thus well suited for use in gene shuffling. Accordingly, the invention provides a method of generating genetic diversity into lipolytic enzymes by family shuffling of two or more homologous genes which encode lipolytic enzymes. The DNA shuffling technique is used to create a library of shuffled genes, and this is expressed in a suitable expression system and the expressed proteins are screened for lipolytic enzyme activity. The expressed proteins may further be screened to identify lipolytic enzymes with improved properties. The invention also provides a polynucleotide comprising a nucleotide sequence encoding a lipolytic enzyme and a lipolytic enzyme (a polypeptide with lipolytic enzyme activity). Excerpt(s): The present invention relates to a method of generating diversity into lipolytic enzymes by the use of the so-called family shuffling of homologous genes. The invention also relates to polynucleotides for use in the method, and to lipolytic enzymes encoded by the polynucleotides. The lipase of Thermomyces lanuginosus (also known as Humicola lanuginosa) is known to be useful for various industrial purposes such as detergents and baking (EP 258068, WO 9404035). Its amino acid and DNA sequences are shown in U.S. Pat. No. 5,869,438. The prior art describes the modification of the amino acid sequence of the T. lanuginosus lipase to create variants with the aim of modifying the enzyme properties. Thus, U.S. Pat. No. 5,869,438, WO 9522615, WO 9704079 and WO 0032758 disclose the use of mutagenesis of the lipase gene to produce such variants. WO 0032758 also discloses the construction of variants with the backbone from T. lanuginosus lipase and C-terminal from Fusarium oxysporum phospholipase by PCR reaction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Lipolytic enzyme variant Inventor(s): Borch, Kim; (Birkerod, DK), Danielsen, Steffen; (Kobenhavn O, DK), Glad, Sanne O. Schroder; (Ballerup, DK), Minning, Steffan; (Frederiksberg C, DK), Vind, Jesper; (Vaerlose, DK) Correspondence: Novozymes North America, INC.; 500 Fifth Avenue; Suite 1600; New York; NY; 10110; US Patent Application Number: 20040152180 Date filed: June 30, 2003 Abstract: Novel lipolytic enzymes are disclosed which are capable of removing substantial amounts of lard from a lard stained swatch in a one cycle wash. Preferred lipolytic enzymes are variants of the Humicola lanuginosa lipase which may be prepared by recombinant DNA techniques. The enzymes are advantageously used in detergent compositions.

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Excerpt(s): The present invention relates to variants of fungal lipolytic enzymes, particularly variants with improved thermostability, and to methods of producing and using such variants. It is known to use fungal lipolytic enzymes, e.g. the lipase from Thermomyces lanuginosus (synonym Humicola lanuginosa), for various industrial purposes, e.g. to improve the efficiency of detergents and to eliminate pitch problems in pulp and paper production. In some situations, a lipolytic enzyme with improved thermostability is desirable (EP 374700, WO 9213130). WO 92/05249, WO 92/19726 and WO 97/07202 disclose variants of the T. lanuginosus (H. lanuginosa) lipase. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for preparing chiral amines Inventor(s): Ahn, Yangsoo; (Seoul, KR), Choi, Yoon Kyung; (Kyungju-city, KR), Kim, Mahn-Joo; (Pohang-city, KR), Kim, Mi Jung; (Bucheon-city, KR) Correspondence: Baker & Botts; 30 Rockefeller Plaza; New York; NY; 10112 Patent Application Number: 20040077864 Date filed: August 5, 2003 Abstract: Disclosed is a method of preparing chiral amine. The method includes reacting ketoxime, palladium, lipase, acyl-donating compound, and tertiary amine to prepare amide, and amide is hydrolyzed. Excerpt(s): The present invention relates to a method of preparing chiral amines, and more preferably, to a method of preparing chiral amines by simple procedures using starting materials which are easy to handle. The procedures for preparing chiral amines are classified into two categories: chemical procedures using metal catalysts and biochemical procedures using an enzyme catalyst. The chemical procedure and the biochemical procedures have complementary advantages and shortcomings. Thus, the combination of the two catalysts has been attempted the preparation of chiral amines. Till now, only one method reported by a German group (Reetz, M. T; Schimossek, K. Chimia, 1996, 50. 668) utilized the enzyme-metal combination for preparing chiral amines. In this method, a chiral amine was prepared as optically pure amide by dynamic kinetic resolution from the mixture of racemic 1-phenylethylamine as a substrate, palladium as a racemization catalyst, and lipase as a selective acylation catalyst. The optically pure amide is formed by selective acylating the desired enantiomer with an acylating agent in the presence of lipase while the other enantiomer is simultaneously racemized in situ by the action of the palladium catalyst. The reaction was performed at a temperature of 50 to 55.degree. C. for 9 days, and the conversion was 75 to 77%. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for preparing flour doughs and products made from such doughs using glycerol oxidase Inventor(s): Madrid, Susan Mampusti; (Vedboek, DK), Poulsen, Charlotte Horsmans; (Bradbrand, DK), Rasmussen, Preben; (Kirke Hyllinge, DK), Soe, Jorn Borch; (Mundelstrup, DK), Zargahi, Masoud R.; (Arhus C., DK) Correspondence: Frommer Lawrence & Haug; 745 Fifth Avenue- 10th FL.; New York; NY; 10151; US Patent Application Number: 20040071853 Date filed: June 16, 2003 Abstract: Method of improving the rheological properties of a flour dough and the quality of bread, alimentary paste products, noodles and cakes wherein glycerol oxidase or a combination of glycerol oxidase and a lipase is added to the dough and dough improving compositions comprising these enzymes. The strength of (B/C ratio) and the gluten index of the dough was improved and in the resulting products the improvements were higher specific volume, increased crumb pore homogeneity and reduced average crumb pore diameter. Excerpt(s): The present invention relates to the field of food manufacturing, in particular to the preparation of improved bakery products and other farinaceous food products. Specifically, the invention concerns the use of glycerol oxidase as a dough strengthening agent and improvement of the quality of baked and dried products made from such improved doughs. There is also provided a method of improving the properties of doughs and baked product by combined use of glycerol oxidase and a lipase. The "strength" or "weakness" of doughs is an important aspect of making farinaceous finished products from doughs, including baking. The "strength" or "weakness" of a dough is primarily determined by its content of protein and in particular the content and the quality of the gluten protein is an important factor in that respect. Flours with a low protein content is generally characterized as "weak". Thus, the cohesive, extensible, rubbery mass which is formed by mixing water and weak flour will usually be highly extensible when subjected to stress, but it will not return to its original dimensions when the stress is removed. Flours with a high protein content are generally characterized as "strong" flours and the mass formed by mixing such a flour and water will be less extensible than the mass formed from a weak flour, and stress which is applied during mixing will be restored without breakdown to a greater extent than is the case with a dough mass formed from a weak flour. Strong flour is generally preferred in most baking contexts because of the superior rheological and handling properties of the dough and the superior form and texture qualities of the finished baked or dried products made from the strong flour dough. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for the production of (1S, 4R)-(-)-4-hydroxy cyclopent-2-enyl esters Inventor(s): Wisdom, Richard; (Hattersheim, DE) Correspondence: Clariant Corporation; Industrial Property Department; 4000 Monroe Road; Charlotte; NC; 28205; US Patent Application Number: 20040126855 Date filed: December 12, 2003

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Abstract: Process for the preparation of (1S, 4R)-4-hydroxy cyclopent-2-enyl esters comprising the steps of:a) reacting a cis-cyclopent-1-ene-3,5-diol, or racemic or a partially resolved4-hydroxy cyclopent-2-enyl ester, with a suitable ester donor in the presence a lipase from Alcaligenes sp. andb) recovering and purifying the produced (1S, 4R)-4-hydroxy cyclopent-2-enyl ester.The reaction is preferably carried out at a temperature in the range from 10.degree. C. to room temperature. Excerpt(s): The instant application refers to a new method for the production of (1S, 4R)(-)-4-hydroxy cyclopent-2-enyl esters, preferably (1S, 4R)-(-)-4-hydroxy cyclopent-2-enyl acetate and -proprionate and its derivatives. (1S, 4R)-(-)-4-Hydroxy cyclopent-2-enyl acetate has been identified as a very useful synthon in the preparation of prostaglandins and other cyclopentanoid products (M. Nara et al, Tetrahedron 36 (1980) 3161; M. Harre et al, Angew. Chemie 94 (1982) 496; Johnson C R. et al., J. Am. Chem. Soc, 115, 1101411015, (1993)). As a result, numerous approaches have been described over the years to prepare this material. Many of these approaches utilise the selective ability of enzymes and, in particular esterases and lipases, to recognise and preferentially produce the preferred enantiomer. Two related enzymatic routes to the required compound have been described. Firstly it is possible to utilise an enzyme to selectively hydrolyse cis-3,5diacetoxy cyclopent-1-ene, which may readily be prepared by the method described by Deardorff (Deardorff et al., Tetrahedron Letters 26, (46), pp 5615-5618 (1985)). Laumen et al. (Laumen et al., Tetrahedron Letters, 25 (51), pp 5875-5878, (1984)) screened a number of enzymes to identify their selectivity. U.S. Pat. No. 4,618,690 describes an example with Pig liver esterase in which a yield of the required enantiomer of 86% on starting cis-3,5-diacetoxy cyclopent-1-ene is obtained, however the ee is only 66%. Although it was possible to increase ee to 86% on one crystalisation and thereafter probably higher on subsequent recrystalisations, this would significantly reduce yields. It is known that commercial preparations of pig liver esterases are a mixture of variants, and it may be that use of a single cloned and expressed variant may give higher selectivity. A recent patent, U.S. Pat. No. 6,448,051 identifies a range of organisms of Trichosporon sp which show high selectivity in their hydrolysis of cis-3,5-diacetoxy cyclopent-1-ene and which produce the required enantiomer of 4-hydroxy cyclopent-2-enyl acetate. Yields of over 80% are described, however in the best case this process uses whole cells at a ratio of 1 part cell biomass to 1 part substrate and the concentrations of product in the biotransformation are less than 1%. Thus as well as the problems of product extraction from aqueous biological solutions, which are known to sometimes cause emulsion problems, the volumetric yields are low. It would be unlikely that the process as described would be suitable for large scale production in a chemical facility. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of purifying crude xanthophylls Inventor(s): Hukami, Tadashi; (Toyama, JP), Ikai, Hisato; (Hisato, JP), Ikushima, Heiji; (Toyama, JP), Nagao, Toshihiro; (Osaka, JP), Shimada, Yuji; (Osaka, JP), Sugihara, Akio; (Hyogo, JP), Tominaga, Yoshio; (Osaka, JP) Correspondence: Flynn Thiel; Boutell & Tanis; 2026 Rambling Road; Kalamazoo; MI; 49008-1699; US Patent Application Number: 20040115758 Date filed: January 15, 2004 Abstract: There is disclosed herein a process for purifying a crude xanthophyll which is characterized by acting a lipase on the crude xanthophyll, which is obtained by

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extracting algae with a solvent, in the present of water under an acidic condition without adjusting the pH whereupon the contaminating neutral lipids (mono-, di- and triglycerides) are selectively hydrolyzed, subjecting the lipase-treated liquor to oil/water separation and removing free fatty acids from the oil layer fractioned thereby elevating the content of xanthophyll. Excerpt(s): The present invention relates to a process for purifying crude xanthophylls, and more particularly it relates to a process for purifying crude xanthophylls, which makes it possible to provide high quality of xanthophylls so that they may be widely used in the fields of a food, a medicine, quasi-drugs, a cosmetic, a cultivation and so on, by hydrolyzing fatty esters of glycerin, principal contaminant derived from the raw material for preparing xanthophylls, with a lypase and removing the resultant hydrolyzate thereby increasing the content of xanthophyll components efficiently and further removing particular odor derived from the raw material. The xanthophylls, one kind of carotenoids are compounds containing one or more hydroxyl groups in the cyclic structure moiety of the molecular skeleton and are present in two or three forms of xanthophyll (free form), mono- and di-esters thereof depending on the number of hydroxyl group. Synthetic xanthophylls or natural ones derived from animal and vegetable are known. As astaxanthin, astaxanthin monoester and astaxanthin diester (hereinafter, referred to as "astaxanthins" collectively) being one of the representative xanthophylls, both the synthetic ones and natural ones derived from animal and vegetable have been commercially sold. Specifically, they may be obtained from an animal such as a crab, a shrimp, a krill and the like by extraction, and they may also be obtained by squeezing oil from algae, for example green algae such as Haematococcus, chlorella, Scenedesmus and the like; from yeasts such as Falfa rhodozyma and the like; or from microorganisms such as bacteria, alternatively by extraction from them through organic solvents such as acetone, ethylacetate, dichloroethane and the like or otherwise an edible oil. The astaxanthins have been expected for utilization as a natural coloring agent, an antioxidant, a health food, a cosmetic and a medicine because they convert into provitamin A after taken in the body and because they have remarkable antioxidant action (Eiji Yamashita; "Food and Development" vol. 27, No. 3, p 38-40 (1992)). Various processes are reported for extracting xanthophylls from a vegetable, green algae, bacteria, cruschimata, etc. If specifically astaxanthins are explained taking as the example, the followings are: a process for extracting astaxanthins with an alkyl ester of a fatty acid (Japanese Patent Application Laid-Open No. Sho 58-88358), a process for extracting them with trichloromonofluoromethane (Japanese Patent Application LaidOpen No. Hei 2-255711), a process wherein a shell of a shrimp or a crab is dipped in hydrochloric acid to remove calcium present in the shell and then the resultant shell is dipped in a sodium hydroxide solution for a neutral treatment and removal of the protein present in the shell and subsequently the resultant shell is dipped in a solvent comprising 80% of alcohol for brewing and 20% of water at a temperature of 78.+.5.degree. C. to separate and extract astaxanthin from the solvent (Japanese Patent Application Laid-Open No. Hei 9-301950), etc. Also, in case of yeasts, there is reported a process wherein the cell walls of yeast after cultivation are broken physically or by acting a cell wall decomposing enzyme thereon and then astaxanthin is extracted from the ruptured cell walls with a mixed solution of hexane and ethanol (Japanese Patent Application Laid-Open No. Hei 7-41687), or a process wherein the cell walls of Falfa rhodozyma yeast are ruptured by heat-treatment at a temperature of 40.degree. C. or more (Japanese Patent Application Laid-Open No. Hei 8-214870). Also, as processes for extracting astaxanthins from algae, for example a process wherein Haematococcus is subjected to a physical rupturing treatment and thereafter astaxanthins are extracted (WO 89/06910), a process wherein the cell walls are ruptured by the application of

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turbulent flow under high pressure and the ruptured cell walls are dried and astaxanthins are extracted with an organic solvent (Japanese Patent Application LaidOpen No. Hei 9-111139) or a process wherein algae containing astaxanthins for example Haematococcus is treated with acetone heated (to 40.degree. C.-boiling point) and then treated with a cell wall decomposing enzyme which comprises the respective components of.beta.-1,3-glucanase,.beta.-1,4-glucanase and.beta.-glucuronidase to extract astaxanthins (Japanese Patent Application Laid-Open No. Hei 11-56346) is reported. In addition, a process for extracting astaxanthins from krill crust in a supercritical state (carbon dioxide) (Japanese Patent Application Laid-Open No. Hei 6200179) or a process for extracting them from bacteria is reported. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for processing crustacean material Inventor(s): Nielsen, Per Munk; (Hillerod, DK) Correspondence: Novozymes North America, INC.; 500 Fifth Avenue; Suite 1600; New York; NY; 10110; US Patent Application Number: 20030185939 Date filed: March 11, 2003 Abstract: The inventor has found that enzymatic treatment of crustaceans with lipolytic enzymes promotes the extraction of coloured pigment. Accordingly, the invention relates to a method for recovering coloured pigment, e.g. astaxanthin, and/or chitin or chitosan and/or lysolecithins from crustaceans. Lipolytic enzyme(s) may e.g. be lipase or phospholipase. The lipolytic enzyme treated crustacean material may be subjected to additional process steps, including treatment with non-lipolytic enzymes such as e.g. protease. The process of the invention provides several suitable products and several uses of such products. Furthermore, the invention also relates to the cosmetic and consumable products (feed and food (including beverages) products and additives produced therefrom. Excerpt(s): The present invention relates to methods for enzymatically processing crustaceans in order to provide useful products therefrom. The usage of carotenoid pigments such as astaxanthin is increasing in the field of food and feed additives as a colorant and/or as an anti-oxidant, in particular for aquacultered fish. Aquatic animals, like terrestrial animals, generally cannot synthesize astaxanthin or other carotenoids but several of these animals, including crustaceans, accumulate astaxanthin present in their diet. Crustaceans have the capability of converting carotenes to astaxanthin. Salmonid fish and red sea bream fish accumulate dietary astaxanthin but these fish cannot convert other carotenes to astaxanthin. Thus, the astaxanthin present in salmonid fish must be derived directly from dietary source. Currently synthetic astaxanthin is employed as feed additive for coloration of farmed fish for providing its desired characteristic reddish colour. However, consumer concerns have resulted in an increased demand for providing natural astaxanthin to substitute the synthetically produced astaxanthin. This should also be seen in the light of the current general preference for natural products. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for using lipases in baking Inventor(s): Golightly, Elizabeth J.; (Davis, CA), Rey, Michael W.; (Davis, CA), Spendler, Tina; (Herlev, DK) Correspondence: Novozymes Biotech, INC.; 1445 Drew Ave; Davis; CA; 95616; US Patent Application Number: 20030180418 Date filed: May 5, 2003 Abstract: The present invention relates to methods for preparing a dough, comprising incorporating into the dough a composition comprising an effective amount of a lipase which improves one or more properties of the dough or a baked product obtained from the dough. The present invention also relates to methods for preparing a baked product. The present invention also relates to compositions comprising an effective amount of such a lipase for improving one or more properties of a dough and/or a baked product obtained from the dough. The present invention further relates to doughs or baked products and to pre-mixes for a dough. Excerpt(s): The present invention relates to methods for preparing a dough and/or baked product with a lipase. The strength of a dough is an important aspect of baking for both small-scale and large-scale applications. A strong dough has a greater tolerance of mixing time, proofing time, and mechanical vibrations during dough transport, whereas a weak dough is less tolerant to these treatments. A strong dough with superior rheological and handling properties results from flour containing a strong gluten network. Flour with a low protein content or a poor gluten quality results in a weak dough. Dough "conditioners" are well known in the baking industry. The addition of conditioners to bread dough has resulted in improved machinability of the dough and improved texture, volume, flavor, and freshness (anti-staling) of the bread. Nonspecific oxidants, such as iodates, peroxides, ascorbic acid, potassium bromate and azodicarbonamide have a gluten strengthening effect. It has been suggested that these conditioners induce the formation of interprotein bonds which strengthen the gluten, and thereby the dough. However, the use of several of the currently available chemical oxidizing agents has been met with consumer resistance or is not permitted by regulatory agencies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Modulation of endothelial lipase expression Inventor(s): Dobie, Kenneth W.; (Del Mar, CA) Correspondence: Marshall, Gerstein & Borun; 6300 Sears Tower; 233 South Wacker Drive; Chicago; IL; 60606-6357; US Patent Application Number: 20040115653 Date filed: December 12, 2002 Abstract: Compounds, compositions and methods are provided for modulating the expression of endothelial lipase. The compositions comprise oligonucleotides, targeted to nucleic acid encoding endothelial lipase. Methods of using these compounds for modulation of endothelial lipase expression and for diagnosis and treatment of disease associated with expression of endothelial lipase are provided. Excerpt(s): The present invention provides compositions and methods for modulating the expression of endothelial lipase. In particular, this invention relates to compounds,

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particularly oligonucleotide compounds, which, in preferred embodiments, hybridize with nucleic acid molecules encoding endothelial lipase. Such compounds are shown herein to modulate the expression of endothelial lipase. Atherosclerosis is the major causative factor of heart disease and stroke, and the leading cause of death in Western countries is cardiovascular disease. Dyslipidaemia is a primary contributor to atherosclerosis. Because triglycerides are insoluble in the bloodstream, they are packaged for plasma transport into micelle-like lipoprotein particles composed of protein and phospholipid shells surrounding a non-polar core of acylglycerols, free cholesterol, and cholesterol esters. Lipoproteins have been classified into five broad categories on the basis of their functional and physical properties: chylomicrons (which transport dietary lipids from intestine to tissues); very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and low density lipoproteins (LDL), (all of which transport triacylglycerols and cholesterol from the liver to tissues); and high density lipoproteins (HDL) (which transport endogenous cholesterol from tissues to the liver, as well as mediating selective cholesteryl ester delivery to steroidogenic tissues). All of these particles undergo continuous metabolic processing and have somewhat variable properties and compositions. Plasma concentrations of LDL and HDL are directly and inversely related, respectively, to the risk of atherosclerotic cardiovascular disease (Krieger, Proc. Natl. Acad. Sci U.S.A. 1998, 95, 4077-4080). HDL protect the arterial wall from the development of atherosclerosis by promoting efflux of excess cholesterol from cells in the arterial wall and returning it to the liver for excretion into the bile, as well as by protecting LDL from oxidation, thereby reducing the inflammatory response of epithelial cells, inhibiting the coagulation pathway, and promoting the availability of nitric oxide. The metabolism of HDL is influenced by several members of the triacylglycerol (TG) lipase family of proteins, which hydrolyze triglycerides, phospholipids and cholesteryl esters, generating fatty acids to facilitate intestinal absorption, energy production or storage. Of the TG lipases, lipoprotein lipase (LPL) influences the metabolism of HDL cholesterol by hydrolyzing triglycerides in triglyceride-rich lipoproteins, resulting in the transfer of lipids and apolipoproteins to HDL and is responsible for hydrolyzing chylomicron and VLDL in muscle and adipose tissues. Hepatic lipase (HL) hydrolyzes HDL triglyceride and phospholipids, generating smaller, lipid-depleted HDL particles, and plays a role in the uptake of HDL cholesterol (Jin et al., Trends Endocrinol. Metab., 2002, 13, 174-178; Wong and Schotz, J. Lipid Res., 2002, 43, 993-999). Endothelial lipase (also known as EDL, EL, LIPG, endothelial-derived lipase and endothelial cell-derived lipase) was identified using differential display to isolate mRNAs which were differentially regulated in response to oxidized-LDL (Jaye et al., Nat. Genet., 1999, 21, 424-428). Independently, the human endothelial lipase gene was identified in human umbilical vein endothelial cells (HUVECs) undergoing tube formation in a model of vascular formation (Hirata et al., J. Biol. Chem., 1999, 274, 1417014175). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel bicyclic inhibitors of hormone sensitive lipase Inventor(s): Heuer, Hubert; (Schwabenheim, DE), Mueller, Guenter; (Sulzbach, DE), Petry, Stefan; (Frankfurt, DE), Tennagels, Norbert; (Frankfurt, DE), Baringhaus, KarlHeinz; (Wolfersheim, DE) Correspondence: Ross J. Oehler; Aventis Pharmaceuticals INC.; Route 202-206; Mail Code: D303a; Bridgewater; NJ; 08807; US Patent Application Number: 20040127484 Date filed: October 14, 2003 Abstract: Benzotriazoles of formula I 1in which R1 to R8 have the abovementioned meanings and process for their preparation are described. The compounds show an inhibitory effect on hormone-sensitive lipase. Excerpt(s): This application claims the benefit of priority of German Patent Application No. 10247680.244, filed Oct. 12, 2002, as well as the benefit of U.S. Provisional Patent Application No. 60/446,913, filed Dec. 12, 2002. in which R1 to R8 have the meanings set forth below, and process for their preparation are described. The compounds show an inhibitory effect on hormone-sensitive lipase. Benzotriazoles are already known from a wide range of fields, such as for example photochemistry (U.S. Pat. No. 4,255,510, Kodak) or as orexin antagonists (WO 02/090355, SKB). Also, the synthesis for preparing benzotriazoles has been described by Katritzky et al. in J. Org. Chem. 1997, 62, 41554158. Also known are carbamates for use as lipase inhibitors such as, for example, Shamkant Patkar et al. in Paul Woolley, Steffen B. Petterson (ed), Lipase (1994) 207-227 or WO 03/051842. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nutritional supplement containing alpha-glucosidase and alpha-amylase inhibitors Inventor(s): Murray, Mary A.; (Irvine, CA), Roh-Schmidt, Haeri; (Ada, MI), Roufs, James B.; (Santa Monica, CA) Correspondence: Brinks Hofer Gilson & Lione; Post Office Box 10395; Chicago; IL; 60610; US Patent Application Number: 20040091554 Date filed: November 7, 2002 Abstract: A nutritional supplement composition contains inhibitors of alpha-glucosidase and alpha-amylase substantially in the absence of lipase inhibitors. The composition can include touchi extract and phaseolamin as the alpha-glucosidase and alpha-amylase inhibitor, respectively. A method of limiting the absorption of carbohydrates contained in a foodstuff includes administering the nutritional supplement composition prior to consumption of the carbohydrates, and a method of promoting weight loss in an individual includes administering the nutritional supplement composition to the individual over a period of days. Excerpt(s): The present invention relates to nutritional supplement compositions containing alpha-glucosidase and alpha-amylase inhibitors. More specifically, the invention relates to nutritional supplement compositions that include effective amounts of alpha-glucosidase and alpha-amylase inhibitors substantially in the absence of lipase inhibitor. The present invention also relates to methods of limiting the absorption of carbohydrates contained in a foodstuff, and to methods of promoting weight loss in an

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individual. Carbohydrates are nutritional compounds that are present in a wide array of foodstuffs. They are a group of numerous different compounds that occur in a variety of sizes and configurations. All carbohydrates are composed of one or more sugar units linked together through glycosidic bonds. Complex carbohydrates, such as starch, are relatively large molecules consisting of numerous repeating units formed into a multibranched chain structure. Monosaccharides and disaccharides, on the other hand, are simple carbohydrates that comprise single and double sugar units, respectively. The human body digests complex carbohydrates by breaking them into relatively simple units, monosaccharides, and then absorbing these units into a tissue, such as the intestine. A variety of digestive enzymes work in a stepwise manner to break the complex carbohydrates into the absorbable units. In an initial step, salivary and pancreatic enzymes known as amylases break large carbohydrates into smaller units of oligo- and disaccharides. In one of the final steps of carbohydrate digestion, alphaglucosidase enzymes in the brush border of the small intestine break the disaccharides maltose and sucrose into their respective monosaccharide units, which can then be absorbed by the body. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Orlistat compositions Inventor(s): Barbier, Pierre; (Rixheim, FR), Hadvary, Paul; (Biel-Benken, CH), Lengsfeld, Hans; (Basle, CH) Correspondence: Hoffmann-La Roche INC.; Patent Law Department; 340 Kingsland Street; Nutley; NJ; 07110 Patent Application Number: 20040105838 Date filed: November 20, 2003 Abstract: A pharmaceutical combination or composition containing a lipase inhibitor, preferably orlistat, and a bile acid sequestrant is useful for treating obesity. Excerpt(s): This application is a divisional of U.S. patent application Ser. No. 09/912,957, filed Jul. 25, 2001, currently pending. The present invention relates to pharmaceutical combinations, compositions and methods for treating obesity. Bile acids are synthesized in the liver and enter the bile as glycine and taurine conjugates. They are released in salt form in bile during digestion and act as detergents to solubilize and consequently aid in digestion of dietary fats. Following digestion, bile acid salts are mostly reabsorbed in the ileum, complexed with proteins, and returned to the liver through the hepatic portal vein. The small amount of bile acid salts which are not reabsorbed by active transport are excreted via the distal ileum and large intestine as a portion of fecal material. Reducing reabsorption of bile acids within the intestinal tract can lower levels of bile acid circulating in the enterohepatic system thereby potentially reducing emulsification in the upper intestinal tract of dietary fat and reducing intestinal absorption of fat soluble drugs. One method of reducing the amount of bile acids that are reabsorbed, is oral administration of compounds that sequester the bile acids within the intestinal tract and cannot themselves be absorbed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pancreatic lipase inhibitor compounds, their synthesis and use Inventor(s): Castelhano, Arlindo; (New City, NY), Witter, David; (Putnam Valley, NY) Correspondence: Cooper & Dunham Llp; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20030195199 Date filed: December 20, 2002 Abstract: The subject invention features compounds having the structure: 1wherein X is O, S, CH.sub.2 or NR.sub.5; Y is O or S; R.sub.1 is H, substituted or unsubstituted C.sub.1-C.sub.15 alkyl, C.sub.1-C.sub.8 alkylaryl, --C(O)OR.sub.4, -C(O)NR.sub.4R.sub.5, --CR.sub.6R.sub.6'OR.su- b.4, --CR.sub.6R.sub.6'OC(O)R.sub.4, -CR.sub.6R.sub.6'OC(O)NHR.sub.7, --C(O)NR.sub.10R.sub.11, --C(O)NR.sub.8R.sub.9 NR.sub.8R.sub.9, --N(R.sub.5)C(O)NHR.sub.5, or CH.sub.2R.sub.4; R.sub.2 is a substituted or unsubstituted, straight chain C.sub.1--C.sub.30 alkyl or branched C.sub.3C.sub.30 alkyl, aryl, alkylaryl, arylalkyl, heteroarylalkyl or cycloalkyl; R.sub.3 is H or substituted or unsubstituted C.sub.1-C.sub.6 alkyl or C.sub.3-C.sub.10 cycloalkyl; R.sub.4 is H or a substituted or unsubstituted, straight chain or branched, C.sub.6C.sub.30 alkyl, aryl, --CH.sub.2-aryl, aryl --C.sub.1-C.sub.15 alkyl, heteroaryl-C.sub.1C.sub.- 15alkyl or C.sub.3-C.sub.10 cycloalkyl; R.sub.5 is H or a substituted or unsubstituted, straight chain or branched, C.sub.6-C.sub.30 alkyl, aryl C.sub.1C.sub.30alkyl, heteroarylalkyl or cycloalkyl; R.sub.6 and R.sub.6' are each independently H, substituted or unsubstituted C.sub.1-C.sub.6 alkyl, dialkyl or C.sub.3-C.sub.10 cycloalkyl or together form a 3-7 membered ring system; R.sub.7 is H or substituted or unsubstituted C.sub.1-C.sub.12 alkyl or C.sub.3-C.sub.10 cycloalkyl; R.sub.8 and R.sub.9 are each independently H, substituted or unsubstituted C.sub.1-C.sub.6 alkyl, C.sub.1C.sub.6 alkoxy, C.sub.1-C.sub.6 alkylaryl, or NR.sub.8R.sub.9 together form a substituted piperazine or piperidine ring or a dihydro-1H-isoquinoline ring system, or a specific enantiomer thereof, or a specific tautomer, or a pharmaceutically acceptable salt thereof and a method for treating diabetes or obesity by administering a therapeutically effective amount of the compounds of the invention. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/342,617, filed Dec. 20, 2001, and U.S. Provisional Application No. 60/357,015, filed Feb. 13, 2002, the entire contents of which are hereby incorporated by reference. Throughout this application, various publications are referenced by full citations. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein. During the last 20 years, obesity has become an increasingly common problem in the populations of developed countries. The increased incidence of obesity is partly due to the adoption of a westernised diet in many developed countries--which contains many foods with high fat and low fiber concentrations--and partly due to the lifestyle of westernized society. Obesity is known to increase the risk of contracting disorders such as diabetes, cardiovascular disease and hypertension. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical compositions containing lipase inhibitors Inventor(s): de Smidt, Passchier Christian; (Pamplona, ES), Hadvary, Paul; (Biel-Benken, CH), Lengsfeld, Hans; (Basle, CH), Rades, Thomas; (Dunedin, NZ), Steffen, Hans; (Liestal, CH), Tardio, Joseph; (St. Louis, FR) Correspondence: Hoffmann-La Roche INC.; Patent Law Department; 340 Kingsland Street; Nutley; NJ; 07110 Patent Application Number: 20030181512 Date filed: April 21, 2003 Abstract: A pharmaceutical composition comprises at least one inhibitor of lipases, preferably an inhibitor of gastrointestinal and pancreatic lipases, such as orlistat, at least one surfactant, and at least one dispersant. Excerpt(s): This application is a continuation of U.S. patent application Ser. No. 09/660,297, filed Sep. 13, 2000, currently pending. The present invention relates to pharmaceutical compositions comprising lipase inhibitors. Examples of lipase inhibitors include lipstatin and orlistat. The latter is also known as tetrahydrolipstatin or THL and is derived from a natural product excreted by Streptomyces toxytricini. This class of compounds was found to exhibit in vitro as well as in vivo activity against various lipases, such as lingual lipase, pancreatic lipase, gastric lipase, and carboxylester lipase. Its use for the control or prevention of obesity and hyperlipidemia is described, for instance, in U.S. Pat. No, 4,598,089. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical use of boronic acids and esters thereof Inventor(s): Ebdrup, Soren; (Roskilde, DK), Jacobsen, Poul; (Slangerup, DK), Vedso, Per; (Frederiksberg, DK) Correspondence: Reza Green, Esq; Novo Nordisk Pharmaceuticals, INC.; 100 College Road West; Princeton; NJ; 08540; US Patent Application Number: 20040053889 Date filed: July 7, 2003 Abstract: Use of compounds to inhibit hormone-sensitive lipase, the use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds, method of treatment employing these compounds and compositions, and novel compounds. The present compounds are inhibitors of hormone-sensitive lipase and may be useful in the treatment and/or prevention of a range of medical disorders where a decreased activity of hormone-sensitive lipase is desirable. Excerpt(s): This application is a continuation of international application PCT/DK03/00315, designating the United States, filed May 14, 2003, claiming priority to Danish application number PA 2002 00902, filed Jun. 14, 2002, the contents of each of which is hereby incorporated by reference herein in its entirety. The present invention relates to use of compounds and pharmaceutical compositions containing them for treating medical disorders where it is desirable to modulate the activity of hormonesensitive lipase. The overall energy homeostasis of a mammalian system requires a high degree of regulation to ensure the availability of the appropriate substrate at the appropriate time. Plasma glucose levels rise during the post-prandial state, to return to pre-prandial levels within 2-3 hours. During these 2-3 hours, insulin promotes glucose

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uptake by skeletal muscle and adipose tissue and decreases the release of free fatty acids (FFA) from adipocytes, to ensure that the two substrates do not compete with each other. When plasma glucose levels fall, an elevation in plasma FFA is necessary to switch from glucose to fat utilization by the various tissues. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Process for preparing (-)- menthol and similar compounds Inventor(s): Brady, Dean; (Midrand, ZA), Chaplin, Jennifer Ann; (San Diego, CA), Evans-Dickson, Melanie Daryle; (Livingstone, ZA), Gardiner, Neil Stockenstrom; (Pretoria, ZA), Marais, Stephanus Francois; (Garsfontein, ZA), Mboniswa, Butana Andrew; (Edenvale, ZA), Mitra, Robin Kumar; (Benoni, ZA), Parkinson, Christopher John; (Modderfontein, ZA), Portwig, Madrie; (Greenside, ZA), Reddy, Shavani; (Edenvale, ZA) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W.; Washington; DC; 20005; US Patent Application Number: 20040058422 Date filed: September 9, 2003 Abstract: A process of separating a desired (-) stereoisomer which is selected from (-) menthol or an equivalent (-) compound where the isopropyl group is replaced with an isopropanol or an isopropylene group, from a starting material comprising: 40 to 100 m/m % of a mixture of (-)-menthol and (+)-menthol; up to 30 m/m % of a mixture of (-)isomenthol and (+)-isomenthol; up to 20 m/m % of a mixture of (-)-neomenthol and (+)neomenthol; and up to 10 m/m % of a mixture of (-)-neoisomenthol and (+)neoisomenthol or an equivalent (+) mixture where the isopropyl group is replaced with an isopropanol or an isopropylene group, includes the steps of: contacting the starting material with an esterifying agent and a stereospecific enzyme which is a Pseudomonas lipase enzyme which stereoselectively esterifies the --OH group of the desired (-) steroisomer, for a time sufficient to convert a desired percentage of the desired (-) stereoisomer to a desired (-) esterified compound where the --OH group is converted to a group --O--C(O)--R4, wherein R4 is an alkyl or an aryl group, to give a first reaction product including the desired (-) esterified compound, the organic solvent, the unconverted stereoisomers, excess esterifying agent and by-products of the reaction; and separating the desired (-) esterified compound from the first reaction product. The process is of particular application for the production of (-)-menthol. Excerpt(s): THIS invention relates to a process for producing (-)-menthol and similar compounds. Menthol has been the subject of much research in the flavour industry. The molecule of menthol has three asymmetric carbon atoms, and hence, a total of eight optically active isomers are possible. The eight isomers are (-)-menthol, (+)-menthol, (-)isomenthol, (+)-isomenthol, (-)-neomenthol, (+)-neomenthol, (-)-neoisomenthol and (+)neoisomenthol. Of all of these isomers only (-)-menthol has a strong refreshing character and is widely used in perfumes and medicines. Thus, the isolation of (-)-menthol from the other isomers is industrially important. As previously discussed, reacemic menthol contains four stereoisomeric pairs of menthols. The isolation of (-)-menthol from this isomeric mixture can be performed chemically via crystallisation, freeze-drying or distillation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Recombinant kid pregastric esterase and methods for its production and use Inventor(s): Bolen, Paul L.; (Middletown, NJ), Cihak, Paul L.; (Leonardo, NJ), Scharpf, Lewis G. JR.; (Fair Haven, NJ) Correspondence: Joseph F. LEIGHTNER. ESQ.; International Flavors & Fragrances INC.; 521 West 57th Street; New York; NY; 10019; US Patent Application Number: 20040001819 Date filed: April 22, 2003 Abstract: The present invention provides kPGE and derivative polypeptides which are capable of being produced by genetic recombination and used to produce EMCs. This invention further provides nucleic acid sequences encoding kPGE and derivative polypeptides which can be used to create recombinant host cells that express kPGE and derivative polypeptides. A further subject of the present of invention is a fusion polypeptide called polyHis-enterokinase which increases expression of esterases and lipases when fused to the N-terminal of the esterase or lipase. This invention also provides a method for treating animals with an esterase or lipase deficiency by administering rkPGE to the animal in a therapeutically effective amount. Excerpt(s): Throughout this specification, various references are identified by a number in parantheses. The citation to the reference corresponding to the identified number can be found in the section entitled References Cited preceding the claims. The references in that section are hereby incorporated by reference. Esterases (also referred to as lipases) are enzymes that cleave triglycerides (fats or lipids) or esters into carboxylic acids (fatty acids) and mono- and di-glycerides. For an explanation of the slightly different definitions given to lipases and esterases see Siezen, R. J. and van den Berg, (37). A pregastric esterase is an esterolytic or lipolytic enzyme secreted by the oral tissues of mammals. Animal esterases in an unpurified form called rennet have been used in the production of dairy food products and, in particular, the production of enzyme modified cheeses or EMCs. (8), (9), (10), (17), (18), (33), (40), and (41). In particular, cheeses like Romano and Provolone have a "peppery" or "piccante flavor due to the fatty acid composition created by the enzyme in the rennet paste. (26), (37). Traditionally EMCs are prepared by esterases obtained from the gullet of slaughtered animals from which a rennet paste or powder is obtained. The rennet is used to treat whey to impart flavor into the cheese product. Kid pregastric estersase (kPGE or kid PGE) in rennet paste is contaminated with proteins which are found in the gullet of the kid and other substances used in the preparation of the rennet. It would be useful to have an uncontaminated kPGE to produce EMC's. Such EMC's could be produced in a manner acceptable to kosher and vegetarian consumers. A recombinant kPGE (rKPGE) could be produced in very pure form free of the other substances found in the present commercial rennet formulations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Recombinant preduodenal lipases and polypeptides derivatives produced by plants, processes for obtaining them and their uses Inventor(s): Baudino, Sylvie; (Lotissement Les Volcans, FR), Benicourt, Claude; (Houilles, FR), Cudrey, Claire; (Gieres, FR), Gruber, Veronique; (Chamilieres, FR), Lenee, Philippe; (Noumea, FR), Merot, Bertrand; (Volvic, FR) Correspondence: Palmer & Dodge, Llp; Kathleen M. Williams; 111 Huntington Avenue; Boston; MA; 02199; US Patent Application Number: 20040072317 Date filed: September 17, 2002 Abstract: The invention concerns the use of recombinant nucleotides sequences containing cDNA coding for a preduodenal lipase, or any sequence derived from this cDNA, for transforming plant cells in order to obtain recombinant preduodenal lipase or polypeptide derivatives.The invention also concerns the use of genetically modified plants or parts thereof, or extracts of these plants or the use of recombinant preduodenal lipase or resultant polypeptide derivatives in the field of foodstuffs, or for producing medicaments, or in industry. Excerpt(s): The present invention relates to the production, by plants, of recombinant preduodenal lipases, in particular recombinant gastric lipases, and to other polypeptide derivatives of these which have a lipase activity, and to their uses, in particular as functional foods or in pharmaceutical compositions or in enzymatic formulations for agro-alimentary or industrial applications. Dog gastric lipase (DGL) is a glycoprotein of 379 amino acids (AA) having a molecular weight of about 50 kilodaltons (kDa), which is synthesized in the form of a precursor containing a signal peptide at the amino-terminal (NH.sub.2-terminal) end and is secreted by median cells of the mucosa of the fundus of the stomach of the dog (Carriere F. et al., 1991). Human gastric lipase (HGL) is naturally synthesized in the form of a precursor and is described in the publication by Bodmer et al., 1987. The mature HGL protein is constituted by 379 amino acids. Its signal peptide (HGLSP) is composed of 19 amino acids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Regulation of human lysosomal acid lipase Inventor(s): Xiao, Yonghong; (Cambridge, MA) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20040038365 Date filed: April 30, 2003 Abstract: Reagents which regulate human lysosomal acid lipase and reagents which bind to human lysosomal acid lipase gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, cancer, CNS disorders, obesity, COPD, diabetes, and cardiovascular disorders. Excerpt(s): This application incorporates by reference Serial No. 60/244,215 filed October 31, 2000, and Serial No. 60/251,401 filed Dec. 6, 2001. The invention relates to the area of lipase enzymes. More particularly, the invention relates to the identification of human lysosomal acid lipase and its regulation. Adipose tissues are repositories of energy in the form of complex, insoluble lipoproteins. The movement of this potential

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energy into energy-requiring cells involves the hydrolysis of the lipoprotein by lipases. In general, triglycerides are the substrate of lipases. The reaction produces lower molecular weight fatty acids and.beta.-mono- and diglycerides. The resultant lipids are absorbed into digestive tract cells with the aid of emulsifying bile acids. The triglycerides are re-synthesized in the endoplasmic reticulum as chylomicrons. See review by Pullinger and Kane, "Lipid Metabolism and Transport," in MOLECULAR BIOLOGY AND BIOTECHNOLOGY, Meyers, ed., VCH Publishers, New York, 1995. The chylomicrons are transported by the lymph system away from the site of absorption. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Triacylglycerol lipases Inventor(s): Cahoon, Edgar B.; (Webster Groves, MO), Cahoon, Rebecca E.; (Webster Groves, MO), Kinney, Anthony J.; (Wilmington, DE), Rafalski, J. Antoni; (Wilmington, DE) Correspondence: E I DU Pont DE Nemours And Company; Legal Patent Records Center; Barley Mill Plaza 25/1128; 4417 Lancaster Pike; Wilmington; DE; 19805; US Patent Application Number: 20040148653 Date filed: February 25, 2004 Abstract: This invention relates to an isolated nucleic acid fragment encoding a triacylglycerol lipase. The invention also relates to the construction of a chimeric gene encoding all or a portion of the triacylglycerol lipase, in sense or antisense orientation, wherein expression of the chimeric gene results in production of altered levels of the triacylglycerol lipase in a transformed host cell. Excerpt(s): This application is a divisional of U.S. application Ser. No. 09/699,652, filed Oct. 30, 2000 which is a continuation of International Application No. PCT/US99/09280, filed Apr. 29, 1999 now expired, which claims the benefit of U.S. Provisional Application No. 60/083,688, filed Apr. 30, 1998 now expired. The entire content of these applications is herein incorporated by reference in their entirety. This invention is in the field of plant molecular biology. More specifically, this invention pertains to nucleic acid fragments encoding triacylglycerol lipases in plants and seeds. True lipases attach triacylglycerols and act at an oil-water interface; they constitute a ubiquitous group of enzymes catalyzing a wide variety of reactions, many with industrial potential. Triacylglycerol lipases catalyze the transformation of triacylglycerol and water into diacylglycerol and a fatty acid anion. Human gastric lipase, rat lingual lipase, and human hepatic lysosomal lipase amino acid sequences are homologous but are unrelated to porcine pancreatic lipase apart from a 6 amino-acid sequence around the essential Ser-152 of porcine pancreatic lipase (Bodmer, M. W. (1987) Biochim Biophys Acta 909:237-244). These enzymes are glycosylated, contain a hydrophobic signal peptide, and belong to a gene family of acid lipases (Ameis, D. et al. (1994) Eur J Biochem 219:905-914). Lysosomal acid lipase (LAL) is a hydrolase essential for the intracellular degradation of cholesteryl esters and triacylglycerols and participates in the mobilization of seed oil during germination. No plant triacylglycerol lipase cDNAs of this class are currently listed in GenBank. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of non-digestible polymeric foams to sequester ingested materials thereby inhibiting their absorption by the body Inventor(s): Hird, Bryn; (Cincinnati, OH), Jandacek, Ronald James; (Cincinnati, 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: 20040091450 Date filed: October 31, 2003 Abstract: This disclosure relates to compositions comprising an open-celled polymeric foam wherein the compositions are useful for sequestering lipophilic materials present in the gastrointestinal tract, thereby inhibiting the absorption of such lipophilic materials by the body. The disclosure further relates to compositions comprising the open-celled polymeric foam wherein the compositions are useful for ameliorating side effects associated with the use of lipase inhibitors. In a preferred embodiment, this disclosure relates to compositions comprising polymeric foam materials made from high internal phase emulsions, where such foams are useful for sequestering lipophilic materials. Further disclosed are compositions comprising open-celled polymeric foams wherein the compositions are useful for the purpose of sequestering aqueous and/or hydrophilic materials present in the gastrointestinal tract, thereby ameliorating diarrhea. Kits comprising the compositions and methods of using the compositions and kits are also described. Excerpt(s): This application claims priority under Title 35, United States Code.sctn. 119(e) from Provisional Application Serial No. 60/277,058, filed Mar. 19, 2001 and under Title 35, United States Code.sctn. 120 from U.S. patent application Ser. No. 10/083,218, filed Feb. 26, 2002 and U.S. patent application Ser. No. 10/251,376, filed Sep. 20, 2002. The present invention relates to compositions comprising an open-celled polymeric foam wherein the compositions are useful for sequestering lipophilic materials present in the gastrointestinal tract, thereby inhibiting the absorption of such lipophilic materials by the body. The invention further relates to compositions comprising the open-celled polymeric foam wherein the compositions are useful for ameliorating side effects associated with the use of lipase inhibitors. This invention further relates to compositions comprising an open-celled polymeric foam wherein the compositions are useful for the purpose of sequestering aqueous and/or hydrophilic materials present in the gastrointestinal tract, thereby ameliorating diarrhea. This invention additionally relates to kits comprising the compositions and methods of using the compositions and kits. Approximately one third of Americans aged 20 to 74 are considered to be obese, and approximately half of Americans in this age group are considered to be overweight. Obesity is also considered to be a growing problem in other industrialized countries and in developing countries where large numbers of people have become accustomed to Western-influenced high-caloric diets. It has been estimated that obesity contributes to 50% of chronic diseases in Western societies and is responsible for approximately 70% of preventable deaths in the U.S.A. Health care costs associated with obesity are substantial. As a result of these factors, the development of compositions to effect weight-loss is the subject of significant commercial interest. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of substituted 3-phenyl-5-alkoxy-3H-(1,3,4)-oxadizol-2-ones for inhibiting pancreatic lipase Inventor(s): Bauer, Armin; (Sulzbach, DE), Heuer, Hubert Otto; (Schwabenheim, DE), Mueller, Guenter; (Sulzbach, DE), Petry, Stefan; (Frankfurt, DE), Schoenafinger, Karl; (Alzenau, DE) Correspondence: Ross J. Oehler; Aventis Pharmaceuticals INC.; Route 202-206; Mail Code: D303a; Bridgewater; NJ; 08807; US Patent Application Number: 20030236288 Date filed: February 28, 2003 Abstract: The invention relates to a method for inhibiting pancreatic lipase, or the prophylaxis or treatment of obesity or diabetes mellitus of type 1 and 2, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of substituted 3-phenyl-5-alkoxy-3H-(1,- 3,4)-oxadiazol-2-ones of formula 1: 1wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are as defined herein, or a prodrug, solvate, pharmacologically acceptable salt or acid addition salt thereof. Excerpt(s): The invention relates to a method for inhibiting pancreatic lipase, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of a substituted 3-phenyl-5-alkoxy-3H-(1,3,4)-oxadiazol-2-one. The invention also relates to a method for the prophylaxis or treatment of obesity or diabetes mellitus of type 1 and 2, in a patient in need thereof, comprising administering to the patient a pharmaceutically effective amount of a substituted 3-phenyl-5-alkoxy-3H(1,3,4)-oxadiazol-2-one. Substituted 3-phenyl-5-alkoxy-3H-(1,3,4)-oxadiazol-2-ones with an inhibitory effect on hormone-sensitive lipase are disclosed in WO 01/17981 and WO 01/66531. The use of substituted 3-phenyl-5-alkoxy-3H-(1,- 3,4)-oxadiazol-2-ones as inhibitors on pancreatic lipase, PL, is not disclosed. R.sup.8 is hydrogen or C.sub.1C.sub.4-alkyl; or a prodrug, solvate, pharmacologically acceptable salt, or acid addition salt thereof. 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 lipase, 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 “lipase” (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 lipase. You can also use this procedure to view pending patent applications concerning lipase. 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 6. BOOKS ON LIPASE Overview This chapter provides bibliographic book references relating to lipase. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on lipase include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

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

Gastric Secretion Source: in Feldman, M.; Friedman, L.S.; Sleisenger, M.H. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. [2-volume set]. St. Louis, MO: Saunders. 2002. p. 715-731. Contact: Available from Elsevier. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 568-5136. Website: www.us.elsevierhealth.com. PRICE: $229.00 plus shipping and handling. ISBN: 0721689736. Summary: This chapter on gastric secretion caused by infection, systemic illness, medications, radiation, and trauma is from a comprehensive and authoritative textbook that covers disorders of the gastrointestinal tract, biliary tree, pancreas, and liver, as well as the related topics of nutrition and peritoneal disorders. Specific topics include physiology, including exocrine epithelial cells, endocrine and neural regulatory cells, the proton pump, parietal cell secretagogues, receptors, and parietal cell inhibitors; quantitative aspects of acid secretion in humans, including development, aging, and

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measurement of acid secretion; mucus and bicarbonate secretion; secretion of other electrolytes; pepsinogens and other gastric aspartic proteases; human gastric lipase; intrinsic factor; and gastric secretion in disease, including diseases associated with increased gastric secretion, diseases associated with decreased gastric secretion, diseases associated with heterotopic gastric acid secretion, and normosecretory acid-related disorders. The chapter includes a mini-outline with page citations, full-color illustrations, and extensive references. 10 figures. 3 tables. 140 references. •

When the Silent Pancreas Speaks Up Source: in Janowitz, H.D. Indigestion: Living Better with Upper Intestinal Problems from Heartburn to Ulcers and Gallstones. New York, NY: Oxford University Press. 1992. p. 136-146. Contact: Available from Oxford University Press. Order Department, 2001 Evans Road, Cary, NC 27513. (800) 451-7556. Fax (919) 677-1303. PRICE: $11.95 plus shipping and handling. ISBN: 019508554X. Summary: This chapter on pancreatic conditions is from a book that offers advice on how to take care of and avoid the whole complex of disturbances categorized as indigestion. The pancreas is a key digestive gland that manufactures digestive enzymes to digest starch (amylase), break down fats (lipase), and digest proteins (trypsinogen and chymotrypsinogen, among others). The pancreas includes the Islets of Langerhans which make the hormones, including insulin (which regulates blood sugar levels and sugar metabolism), glucagon (which raises blood sugar), somatostatin (which turns off the intestinal juices), and vasoactive intestinal polypeptide (which turns off stomach juices, silences the gallbladder, and stimulates the intestines). The author notes that the pancreas is very sensitive to the action of certain drugs, alcohol, caffeine, and trouble in the gallbladder. The pancreas can malfunction as acute pancreatitis or in a slower more insidious form known as chronic pancreatitis. The author reviews the risk factors for pancreatitis, the symptoms of acute and chronic difficulties with the pancreas, the causes of pancreatitis, diagnostic considerations, and treatment for acute pancreatitis. The pancreas has great recuperative properties that can restore it even after a severe attack. The individual who has recovered from pancreatitis need not suffer any chronic disturbance in digestion or metabolism, provided that no further damage is done to the gland again. If repeatedly insulted, however, by alcohol, undiagnosed gallbladder disease, toxic drugs, or uncorrected metabolic diseases, the pancreas can develop serious problems leading to diabetes or malnutrition.

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Serum Enzyme Levels Source: in Daugirdas, J.T. and Ing, T.S., eds. Handbook of Dialysis. 2nd ed. Boston, MA: Little, Brown and Company. 1994. p. 416-421. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 777-2295. Fax (301) 824-7390. E-mail: [email protected]. Website: http://www.lrpub.com. PRICE: $37.95. ISBN: 0316173835. Summary: This chapter on serum enzyme levels is from a handbook that outlines all aspects of dialysis therapy, emphasizing the management of dialysis patients. Topics include acute myocardial infarction (MI) and creatinine kinase, aspartate aminotransferase, and lactic dehydrogenase; enzymes associated with hepatic disease, including alanine and aspartate aminotransferases, alkaline phosphatase, and other hepatobiliary enzymes; enzymes associated with pancreatitis, including amylase, lipase,

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serum pancreatic secretory trypsin inhibitor (PSTI), and serum trypsin. The authors present information in outline form, for easy reference. 1 table. 18 references.

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CHAPTER 7. MULTIMEDIA ON LIPASE Overview In this chapter, we show you how to keep current on multimedia sources of information on lipase. 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 lipase is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “lipase” 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 “lipase” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on lipase: •

Gender, Genetics, and Obesity Source: Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, 1992, 60 minutes. Contact: WIN, 1 WIN WAY, Bethesda, MD 20892-3665. Summary: In this lecture, Dr. Greenwood discusses current understanding of the impact of gender and genetics on obesity and describes animal and human studies that offer clues about why it is so difficult to treat obesity. Data strongly suggest that increased incidence and prevalence of obesity in the United States is not caused solely by increased caloric intake. Dr. Greenwood describes the different patterns of obesity that tend to occur in men and in women and evidence from various studies suggesting that fat distribution may be the factor contributing most to the health risk of obesity. The lecture goes on to discuss animal models that suggest the vulnerability to obesity may be the result of aberrant nutrition partitioning, whereby a higher than normal proportion of nutrients are deposited in fatty tissue, leaving other tissues (notably skeletal muscle) relatively deprived. Dr. Greenwood and her colleagues propose that

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overeating is an adaptive response to this process, which they believe may be regulated by lipoprotein lipase, an enzyme manufactured by fat cells. Dr. Greenwood also examines research on weight cycling, a phenomenon in which an individual loses weight, gains it back, loses it again, and so on. Evidence gleaned from studies in both rats and humans suggests that weight cycling may be an independent risk factor for increased morbidity and mortality, and may also be associated with the decreased effectiveness of weight loss methods. However, Dr. Greenwood notes that no long-term studies have been conducted on the effects of weight cycling, and that this is an important area for future research. The lecture concludes with the observation that weight loss advice should address the need for physical fitness and permanent lifestyle change and diet composition over caloric restriction.

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CHAPTER 8. PERIODICALS AND NEWS ON LIPASE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover lipase.

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

Atorvastatin decreases hepatic lipase activity in diabetes Source: Reuters Industry Breifing Date: March 07, 2003

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Dietary fat intake determines effects of hepatic lipase gene mutation Source: Reuters Medical News Date: October 21, 2002

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Low hepatic lipase activity tied to increased heart disease risk Source: Reuters Medical News Date: December 17, 2001

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Lipoprotein lipase mutation raises stroke risk in women Source: Reuters Medical News Date: May 23, 2000

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Hormone-sensitive lipase required for spermatogenesis in mice Source: Reuters Medical News Date: January 18, 2000

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ACOG 1999: Lipase inhibition shows long-term efficacy in weight loss Source: Reuters Medical News Date: May 19, 1999

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Newly identified lipase regulates HDL and may have vascular role Source: Reuters Medical News Date: March 30, 1999

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Diet modification plus lipase may treat pancreatic steatorrhea Source: Reuters Medical News Date: February 19, 1999

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Progenitor Scientists Discover Lipoprotein Lipase Gene Source: Reuters Medical News Date: March 31, 1998

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Lipoprotein Lipase Variant Linked To Coronary Disease Progression Source: Reuters Medical News Date: March 23, 1998

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Mutant Lipoprotein Lipase Gene Linked To Heart Disease Risk Source: Reuters Medical News Date: September 16, 1997

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Lipoprotein Lipase Gene Mutations Cause Of Premature Atherosclerosis Source: Reuters Medical News Date: September 19, 1996 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.

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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 “lipase” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “lipase” (or synonyms). If you know the name of a company that is relevant to lipase, 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 “lipase” (or synonyms).

Academic Periodicals covering Lipase Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to lipase. In addition to these sources, you can search for articles covering lipase 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 9. 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 lipase. 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 lipase. 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 lipase: Orlistat •

Oralâ€”Local - U.S. Brands: Xenical http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500006.html

Pancrelipase •

Systemic - U.S. Brands: Cotazym; Cotazym-S; Creon 10; Creon 20; Creon 5; Enzymase-16; Ilozyme; Ku-Zyme HP; Pancoate; Pancrease; Pancrease MT 10; Pancrease MT 16; Pancrease MT 20; Pancrease MT 4; Panokase; Protilase; Ultrase MT 12; Ultrase MT 20; Viokase; Zymase http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202436.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •

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

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

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

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

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

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

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

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

10

These publications are typically written by one or more of the various NIH Institutes.

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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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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.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

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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

11

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

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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 Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “lipase” (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 22551 75 19 52 112 22809

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “lipase” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

18 Adapted 19

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on lipase 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 lipase. 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 lipase. 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 “lipase”:

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Laboratory Tests http://www.nlm.nih.gov/medlineplus/laboratorytests.html Liver Diseases http://www.nlm.nih.gov/medlineplus/liverdiseases.html Metabolic Disorders http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html Pancreatic Diseases http://www.nlm.nih.gov/medlineplus/pancreaticdiseases.html Preventing Disease and Staying Healthy http://www.nlm.nih.gov/medlineplus/preventingdiseaseandstayinghealthy.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 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 lipase. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

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

•

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

•

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

•

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

•

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

•

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

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to lipase. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with lipase. 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 lipase. 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 “lipase” (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 “lipase”. 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 “lipase” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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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 “lipase” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

21

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

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

•

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

•

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

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

22

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

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

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

•

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

•

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

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

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

•

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

•

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

•

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

•

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

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

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

•

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

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

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

•

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

•

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

•

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

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

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

•

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

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

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

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

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

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

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/

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•

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

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

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 lipase: •

Basic Guidelines for Lipase Lipase test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003465.htm

•

Signs & Symptoms for Lipase Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm

•

Diagnostics and Tests for Lipase Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm Triglycerides Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003493.htm Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm

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•

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Background Topics for Lipase Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Enzyme Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002353.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.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

249

LIPASE 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] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] 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]

Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Acetyltransferases: Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine

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derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself 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] 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] 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] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal insufficiency: The reduced secretion of adrenal glands. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [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] Adrenergic Agents: Drugs that act on adrenergic receptors or affect the life cycle of adrenergic transmitters. Included here are adrenergic agonists and antagonists and agents that affect the synthesis, storage, uptake, metabolism, or release of adrenergic transmitters. [NIH]

Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [NIH] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] 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] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the

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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] Aflatoxins: A group of closely related toxic metabolites that are designated mycotoxins. They are produced by Aspergillus flavus and A. parasiticus. Members of the group include aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, aflatoxin M1, and aflatoxin M2. [NIH] 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 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] 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] Alcaligenes: A genus of gram-negative, aerobic, motile bacteria that occur in water and soil. Some are common inhabitants of the intestinal tract of vertebrates. These bacteria occasionally cause opportunistic infections in humans. [NIH] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] 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

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to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allopurinol: A xanthine oxidase inhibitor that decreases uric acid production. [NIH] Alloys: A mixture of metallic elements or compounds with other metallic or metalloid elements in varying proportions. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-Amylase: An enzyme that catalyzes the endohydrolysis of 1,4-alpha-glycosidic linkages in starch, glycogen, and related polysaccharides and oligosaccharides containing 3 or more 1,4-alpha-linked D-glucose units. EC 3.2.1.1. [NIH] Alpha-Linolenic Acid: A fatty acid that is found in plants and involved in the formation of prostaglandins. [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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric

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acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [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] Amylase: An enzyme that helps the body digest starches. [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] Amylopectin: A highly branched glucan in starch. [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] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] 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] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH]

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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] 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] Anhydrous: Deprived or destitute of water. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [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] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH]

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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] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimetastatic: Having to do with reducing 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] Antiproliferative: Counteracting a process of proliferation. [EU] Antipruritic: Relieving or preventing itching. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [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

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very-high-density lipoprotein fraction (HDL, VHDL). They consist of several different 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] 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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] 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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] 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] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH]

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Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] 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] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] 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] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Avian: A plasmodial infection in birds. [NIH] Axilla: The underarm or armpit. [NIH] Backcross: A cross between a hybrid and either one of its parents. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH]

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Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] 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] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [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] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomass: Total mass of all the organisms of a given type and/or in a given area. (From Concise Dictionary of Biology, 1990) It includes the yield of vegetative mass produced from any given crop. [NIH]

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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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood 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] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [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 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 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]

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Boronic Acids: Inorganic or organic compounds that contain the basic structure RB(OH)2. [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] 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 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] Breast Feeding: The nursing of an infant at the mother's breast. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Burkholderia: A genus of gram-negative, aerobic, rod-shaped bacteria. Organisms in this genus had originally been classified as members of the Pseudomonas genus but overwhelming biochemical and chemical findings indicated the need to separate them from other Pseudomonas species, and hence, this new genus was created. [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] 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 Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH]

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Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency, or other output. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capping: A 7-methyl guanosine cap attached to the 5'-end of eucaryotic mRNAs by a phosphodiester linkage. The cap is believed to increase the stability of the message, since most nucleases require a 5'-3'or 3'-5'bond in order to cleave the RNA. [NIH] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH]

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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] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular Agents: Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalyse: To speed up a chemical reaction. [EU] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [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]

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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 motility: The ability of a cell to move. [NIH] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] 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 Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central fat distribution: The waist circumference is an index of body fat distribution. Increasing waist circumference is accompanied by increasing frequencies of overt type 2 diabetes, dyslipidemia, hypertension, coronary heart disease, stroke, and early mortality. In the body fat patterns called android type (apple shaped) fat is deposited around the waist and upper abdominal area and appears most often in men. Abdominal body fat is thought to be associated with a rapid mobilization of fatty acids rather than resulting from other fat depots, although it remains a point of contention. If abdominal fat is indeed more active than other fat depots, it would then provide a mechanism by which we could explain (in part) the increase in blood lipid and glucose levels. The latter have been clearly associated with an increased risk for cardiovascular disease, hypertension, and type 2 diabetes. The gynoid type (pear-shaped) of body fat is usually seen in women. The fat is deposited around the hips, thighs, and buttocks, and presumably is used as energy reserve during pregnancy and lactation. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] 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

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brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Ceroid: A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions. [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] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chlorella: Nonmotile unicellular green algae potentially valuable as a source of high-grade protein and B-complex vitamins. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chlorpyrifos: An organothiophosphate cholinesterase inhibitor that is used as an insecticide and as an acaricide. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esterase: An enzyme that catalyzes the hydrolysis of cholesterol and some other sterol esters, to liberate cholesterol plus a fatty acid anion. EC 3.1.1.13. [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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [NIH]

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Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [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] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Coculture: The culturing of normal cells or tissues with infected or latently infected cells or tissues of the same kind (From Dorland, 28th ed, entry for cocultivation). It also includes culturing of normal cells or tissues with other normal cells or tissues. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] 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] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH]

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Coliphages: Viruses whose host is Escherichia coli. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colostrum: The thin, yellow, serous fluid secreted by the mammary glands during pregnancy and immediately postpartum before lactation begins. It consists of immunologically active substances, white blood cells, water, protein, fat, and carbohydrates. [NIH]

Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [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

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addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confidence Intervals: A range of values for a variable of interest, e.g., a rate, constructed so that this range has a specified probability of including the true value of the variable. [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

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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] 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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] 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 medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] 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] 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] 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] Corn Oil: Oil from corn or corn plant. [NIH]

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Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Angiography: Radiography of the vascular system of the heart muscle after injection of a contrast medium. [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] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [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] 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]

Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] 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]

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Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [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] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]

De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] 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] Defecation: The normal process of elimination of fecal material from the rectum. [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] 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] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule

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cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [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] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dexfenfluramine: The S-isomer of fenfluramine. It is a serotonin agonist and is used as an anorectic. Unlike fenfluramine, it does not possess any catecholamine agonist activity. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [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] 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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] Diazinon: A cholinesterase inhibitor that is used as an organothiophosphorus insecticide. [NIH]

Dichlorvos: An organophosphorus insecticide that inhibits acetylcholinesterase. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH]

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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]

Dietary Fiber: The remnants of plant cell walls that are resistant to digestion by the alimentary enzymes of man. It comprises various polysaccharides and lignins. [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 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] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disaccharides: Sugars composed of two monosaccharides linked by glycoside bonds. [NIH] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disease Vectors: Invertebrates or non-human vertebrates which transmit infective organisms from one host to another. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Docosahexaenoic Acids: C22-unsaturated fatty acids found predominantly in fish oils. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the

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extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxazosin: A selective alpha-1-adrenergic blocker that lowers serum cholesterol. It is also effective in the treatment of hypertension. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [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 Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenal Ulcer: An ulcer in the lining of the first part of the small intestine (duodenum). [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] 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] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU]

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Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]

Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins. [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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emulsify: To convert or to be converted into an emulsion. [EU] 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]

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Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [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] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [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] Energy deficit: A state in which total energy intake is less than total energy need. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enteric-coated: A term designating a special coating applied to tablets or capsules which prevents release and absorption of their contents until they reach the intestines. [EU] Enterohepatic: Of or involving the intestine and liver. [EU] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]

Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health.

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[NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Activators: Compounds or factors that act on a specific enzyme to increase its activity. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [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] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes. [NIH]

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Estrogen: One of the two female sex hormones. [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] Ethanolamine: A viscous, hygroscopic amino alcohol with an ammoniacal odor. It is widely distributed in biological tissue and is a component of lecithin. It is used as a surfactant, fluorimetric reagent, and to remove CO2 and H2S from natural gas and other gases. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Euphorbiaceae: The spurge family of flowering plants, in the order Euphorbiales, contains some 7,500 species in 275 genera. The family consists of annual and perennial herbs and woody shrubs or trees. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] 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 Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of

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protein, cells, or solid materials derived from cells. [EU] 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] 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] Fat Body: A nutritional reservoir of fatty tissue found mainly in insects and amphibians. [NIH]

Fat Necrosis: A condition in which the death of adipose tissue results in neutral fats being split into fatty acids and glycerol. [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 Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [NIH] Fecal Incontinence: Failure of voluntary control of the anal sphincters, with involuntary passage of feces and flatus. [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] Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [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] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fish Oils: Oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the livers. Those from the liver are usually high in vitamin A. The oils are used as dietary supplements, in soaps and detergents, as protective coatings, and as a base for other food products such as vegetable shortenings. [NIH] Flatus: Gas passed through the rectum. [NIH]

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Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]

Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [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] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Food Additives: Substances which are of little or no nutritive value, but are used in the processing or storage of foods or animal feed, especially in the developed countries; includes antioxidants, food preservatives, food coloring agents, flavoring agents, anti-infective agents (both plain and local), vehicles, excipients and other similarly used substances. Many of the same substances are pharmaceutic aids when added to pharmaceuticals rather than to foods. [NIH]

Food Coloring Agents: Natural or synthetic dyes used as coloring agents in processed foods. [NIH] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Freeze Drying: Method of tissue preparation in which the tissue specimen is frozen and then dehydrated at low temperature in a high vacuum. This method is also used for dehydrating pharmaceutical and food products. [NIH] Freeze-dried: A method used to dry substances, such as food, to make them last longer. The substance is frozen and then dried in a vacuum. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some

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reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [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] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Inhibitory Polypeptide: A gastrointestinal hormone consisting of a 43-amino acid polypeptide (molecular weight 5105). It inhibits gastric secretion and motility and stimulates release of insulin. [NIH] Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelsolin: A 90-kD protein produced by macrophages that severs actin filaments and forms a cap on the newly exposed filament end. Gelsolin is activated by calcium ions and participates in the assembly and disassembly of actin, thereby increasing the motility of some cells. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease

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by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] 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

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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] Glucosylceramidase: A glycosidase that hydrolyzes a glucosylceramide to yield free ceramide plus glucose. Deficiency of this enzyme leads to abnormally high concentrations of glucosylceramide in the brain in Gaucher's disease. EC 3.2.1.45. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] 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] Glyceryl Ethers: Compounds in which one or more of the three hydroxyl groups of glycerol are in ethereal linkage with a saturated or unsaturated aliphatic alcohol; one or two of the hydroxyl groups of glycerol may be esterified. These compounds have been found in various animal tissue. [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] 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] Glycogen Storage Disease: A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any

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such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] 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] Glycosylceramidase: The enzyme hydrolyzing glycosyl-N-acylsphingosine to a sugar and N-acylsphingosine. It also catalyzes the hydrolysis of phlorizin to phloretin and glucose. It is found in the intestinal brush border membrane often in conjunction with lactase. EC 3.2.1.62. [NIH]

Gonadal: Pertaining to a gonad. [EU] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [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] 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-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [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] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody

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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] 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] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [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] 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]

Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [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] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatocyte: A liver cell. [NIH] Hepatoma: A liver tumor. [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] 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]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [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

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entorhinal cortex in the hippocampal formation. [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] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [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] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic 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] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive

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isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] 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] 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] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [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] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertension, Renal: Hypertension due to renal diseases, especially chronic parenchymal disease. Hypertension as a result of compression or obstruction of the renal artery or its branches is hypertension, renovascular. [NIH] Hypertension, Renovascular: Hypertension due to compression or obstruction of the renal artery or its branches. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [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] 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] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild

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symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Ice Cream: A frozen dairy food made from cream or butterfat, milk, sugar, and flavorings. Frozen custard and French-type ice creams also contain eggs. [NIH] Ileum: The lower end of the small intestine. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] 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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] 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] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH]

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Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] 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]

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]

Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been

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identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inositol 1,4,5-Trisphosphate: Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. [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] Insomnia: Difficulty in going to sleep or getting enough sleep. [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] Interindividual: Occurring between two or more individuals. [EU] 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] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravascular: Within a vessel or vessels. [EU]

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Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intrinsic Factor: A glycoprotein secreted by the cells of the gastric glands that is required for the absorption of vitamin B 12. Deficiency of intrinsic factor results in pernicious anemia. [NIH]

Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Iodates: Inorganic salts of iodic acid (HIO3). [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] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Islet: Cell producing insulin in pancreas. [NIH] Isoamylase: An enzyme that hydrolyzes 1,6-alpha-glucosidic branch linkages in glycogen, amylopectin, and their beta-limit dextrins. It is distinguished from pullulanase (EC 3.2.1.41) by its inability to attack pullulan and by the feeble action of alpha-limit dextrins. It is distinguished from amylopectin 6-glucanohydrolase (EC 3.2.1.69) by its action on glycogen. With EC 3.2.1.69, it produces the activity called "debranching enzyme". EC 3.2.1.68. [NIH] Isoelectric: Separation of amphoteric substances, dissolved in water, based on their isoelectric behavior. The amphoteric substances are a mixture of proteins to be separated and of auxiliary "carrier ampholytes". [NIH] Isoelectric Point: The pH in solutions of proteins and related compounds at which the

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dipolar ions are at a maximum. [NIH] Isoenzymes: One of various structurally related forms of an enzyme, each having the same mechanism but with differing chemical, physical, or immunological characteristics. [NIH] Isopropyl: A gene mutation inducer. [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] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] 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] Kinetic: Pertaining to or producing motion. [EU] 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] 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] 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] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH]

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Lincomycin: (2S-trans)-Methyl 6,8-dideoxy-6-(((1-methyl-4-propyl-2pyrrolidinyl)carbonyl)amino)-1-thio-D-erythro-alpha-D-galacto-octopyranoside. An antibiotic produced by Streptomyces lincolnensis var. lincolnensis. It has been used in the treatment of staphylococcal, streptococcal, and Bacteroides fragilis infections. [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] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipaemia: The presence of an excess of fats or lipids in the blood. [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] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipofuscin: A naturally occurring lipid pigment with histochemical characteristics similar to ceroid. It accumulates in various normal tissues and apparently increases in quantity with age. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34. [NIH] Lipoprotein(a): A family of lipoprotein particles varying in density and size depending on the protein-lipid ratio and the protein composition. These particles consist of apolipoprotein B-100 covalently linked to apolipoprotein-a by one or two disulfide bonds. There is a correlation between high plasma levels of this lipoprotein and increased risk for atherosclerotic cardiovascular disease. [NIH] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH]

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Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liquor: 1. A liquid, especially an aqueous solution containing a medicinal substance. 2. A general term used in anatomical nomenclature for certain fluids of the body. [EU] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [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] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] 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] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells

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that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] 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] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysophospholipase: An enzyme that catalyzes the hydrolysis of a single fatty acid ester bond in lysoglycerophosphatidates with the formation of glyceryl phosphatidates and a fatty acid. EC 3.1.1.5. [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] Macroglia: A type of neuroglia composed of astrocytes. [NIH] 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] 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 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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption Syndromes: General term for syndromes of malnutrition due to failure of normal intestinal absorption of nutrients. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Marijuana Abuse: The excessive use of marijuana with associated psychological symptoms and impairment in social or occupational functioning. [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.

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[NIH]

Meat Products: Articles of food which are derived by a process of manufacture from any portion of carcasses of any animal used for food (e.g., head cheese, sausage, scrapple). [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] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fluidity: The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Menthol: An alcohol produced from mint oils or prepared synthetically. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Metabolic acidosis: (met-ah-BOL-ik as-id-O-sis): A condition in which the blood is too acidic. It may be caused by severe illness or sepsis (bacteria in the bloodstream). [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH]

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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] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [NIH] 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] Micelle: A colloid particle formed by an aggregation of small molecules. [EU] 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] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [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] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] 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] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative

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procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] 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] Monensin: An antiprotozoal agent produced by Streptomyces cinnamonensis. It exerts its effect during the development of first-generation trophozoites into first-generation schizonts within the intestinal epithelial cells. It does not interfere with hosts' development of acquired immunity to the majority of coccidial species. Monensin is a sodium and proton selective ionophore and is widely used as such in biochemical studies. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [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] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells,

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water, inorganic salts, and exfoliated cells. [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] Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Mycotoxins: Toxins derived from bacteria or fungi. [NIH] Myelin: The fatty substance that covers and protects nerves. [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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] 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] 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] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH]

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Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [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] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Regeneration: Renewal or physiological repair of damaged nerve tissue. [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, as the neutral arch. [EU] Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell. [NIH] Neuroeffector Junction: The synapse between a neuron (presynaptic) and an effector cell other than another neuron (postsynaptic). Neuroeffector junctions include synapses onto muscles and onto secretory cells. [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] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [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]

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Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] 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] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [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] 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] 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] 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] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH]

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Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Nutritive Value: An indication of the contribution of a food to the nutrient content of the diet. This value depends on the quantity of a food which is digested and absorbed and the amounts of the essential nutrients (protein, fat, carbohydrate, minerals, vitamins) which it contains. This value can be affected by soil and growing conditions, handling and storage, and processing. [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] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] 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] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orlistat: A lipase inhibitor used for weight loss. Lipase is an enzyme found in the bowel that assists in lipid absorption by the body. Orlistat blocks this enzyme, reducing the amount of fat the body absorbs by about 30 percent. It is known colloquially as a "fat blocker." Because more oily fat is left in the bowel to be excreted, Orlistat can cause an oily anal leakage and fecal incontinence. Orlistat may not be suitable for people with bowel conditions such as irritable bowel syndrome or Crohn's disease. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more

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concentrated side of a semipermeable membrane. [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] 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] 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] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [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]

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Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Ducts: Ducts that collect pancreatic juice from the pancreas and supply it to the duodenum. [NIH] Pancreatic enzymes: A group of proteins secreted by the pancreas which aid in the digestion of food. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]

Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatin: A mammalian pancreatic extract composed of enzymes with protease, amylase and lipase activities. It is used as a digestant in pancreatic malfunction. [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] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Pentoxifylline: A methylxanthine derivative that inhibits phosphodiesterase and affects blood rheology. It improves blood flow by increasing erythrocyte and leukocyte flexibility. It also inhibits platelet aggregation. Pentoxifylline modulates immunologic activity by

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stimulating cytokine production. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsinogens: Proenzymes secreted by chief cells, mucous neck cells, and pyloric gland cells, which are converted into pepsin in the presence of gastric acid or pepsin itself. (Dorland, 28th ed) In humans there are 2 related pepsinogen systems: pepsinogen A (formerly pepsinogen I or pepsinogen) and pepsinogen C (formerly pepsinogen II or progastricsin). Pepsinogen B is the name of a pepsinogen from pigs. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Perciformes: The most diversified of all fish orders and the largest vertebrate order. It includes many of the commonly known fish such as porgies, croakers, mullets, dolphin fish, etc. [NIH] 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] 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] Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] 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] Perivascular: Situated around a vessel. [EU] Pernicious anemia: A type of anemia (low red blood cell count) caused by the body's inability to absorb vitamin B12. [NIH] Peroneal Nerve: The lateral of the two terminal branches of the sciatic nerve. The peroneal

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(or fibular) nerve provides motor and sensory innervation to parts of the leg and foot. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmaceutic Aids: Substances which are of little or no therapeutic value, but are necessary in the manufacture, compounding, storage, etc., of pharmaceutical preparations or drug dosage forms. They include solvents, diluting agents, and suspending agents, and emulsifying agents. Also, antioxidants; preservatives, pharmaceutical; dyes (coloring agents); flavoring agents; vehicles; excipients; ointment bases. [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] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phosphates: Inorganic salts of phosphoric acid. [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] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the

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cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipases A: Phosphatide acylhydrolases. Catalyze the hydrolysis of one of the acyl groups of phosphoglycerides or glycerophosphatidates. Phospholipase A1 hydrolyzes the acyl group attached to the 1-position (EC 3.1.1.32) and phospholipase A2 hydrolyzes the acyl group attached to the 2-position (EC 3.1.1.4). [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [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] Phosphorylase a: The phosphorylated and more active form of phosphorylase that functions as a regulatory enzyme during glycogen breakdown. The phosphate groups are hydrolytically removed by phosphorylase phosphatase to form phosphorylase B and orthophosphate. EC 2.4.1.-. [NIH] Phosphorylase b: The relatively inactive form of phosphorylase that is reactivated to form phosphorylase A by phosphorylase kinase, which catalyzes the enzymatic phosphorylation of the serine residues at the expense of ATP. [NIH] Phosphorylase Kinase: An enzyme that catalyzes the conversion of ATP and phosphorylase b to ADP and phosphorylase a. EC 2.7.1.38. [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] Physical Fitness: A state of well-being in which performance is optimal, often as a result of physical conditioning which may be prescribed for disease therapy. [NIH] Physicochemical: Pertaining to physics and chemistry. [EU] 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] Phytotoxin: A substance which is toxic for plants. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH]

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Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected 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] Plant Oils: Oils derived from plants or plant products. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized 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] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] 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]

Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or

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veins. [EU] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyesters: Polymers of organic acids and alcohols, with ester linkages--usually polyethylene terephthalate; can be cured into hard plastic, films or tapes, or fibers which can be woven into fabrics, meshes or velours. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

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] 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] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] 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] Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] 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

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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 (hydroxymethylglutaryl CoA reductases). [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Preeclampsia: A toxaemia of late pregnancy characterized by hypertension, edema, and proteinuria, when convulsions and coma are associated, it is called eclampsia. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [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] 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] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] 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] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior

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pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones, in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propionibacterium: A genus of gram-positive, rod-shaped bacteria whose cells occur singly, in pairs or short chains, in V or Y configurations, or in clumps resembling letters of the Chinese alphabet. Its organisms are found in cheese and dairy products as well as on human skin and can occasionally cause soft tissue infections. [NIH] Propionibacterium acnes: A bacteria isolated from normal skin, intestinal contents, wounds, blood, pus, and soft tissue abscesses. It is a common contaminant of clinical specimens, presumably from the skin of patients or attendants. [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] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] 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] 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 Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [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] 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

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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] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] 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]

Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are

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known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] 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] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [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] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [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] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH]

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Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [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] Renal Artery: A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. [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] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Resting metabolic rate: RMR accounts for 65 to 75 percent of daily energy expenditure and represents the minimum energy needed to maintain all physiological cell functions in the resting state. The principal determinant of RMR is lean body mass (LBM). Obese subjects have a higher RMR in absolute terms than lean individuals, an equivalent RMR when corrected for LBM and per unit surface area, and a lower RMR when expressed per kilogram of body weight. Obese persons require more energy for any given activity because of a larger mass, but they tend to be more sedentary than lean subjects. [NIH] Restitution: The restoration to a normal state. [NIH]

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Reticulata: Part of substantia nigra. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] 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] Retinyl palmitate: A drug being studied in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Rheology: The study of the deformation and flow of matter, usually liquids or fluids, and of the plastic flow of solids. The concept covers consistency, dilatancy, liquefaction, resistance to flow, shearing, thixotrophy, and viscosity. [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] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] 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] Ricin: A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU]

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Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] 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] Salicylic: A tuberculosis drug. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] 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] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] 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] Sciatic Nerve: A nerve which originates in the lumbar and sacral spinal cord (L4 to S3) and supplies motor and sensory innervation to the lower extremity. The sciatic nerve, which is the main continuation of the sacral plexus, is the largest nerve in the body. It has two major branches, the tibial nerve and the peroneal nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sea Bream: A species of perciformes commonly used in saline aquaculture. [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]

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Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [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] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [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] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Sibutramine: A drug used for the management of obesity that helps reduce food intake and is indicated for weight loss and maintenance of weight loss when used in conjunction with a reduced-calorie diet. It works to suppress the appetite primarily by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin. Side effects include dry mouth, headache, constipation, insomnia, and a slight increase in average blood pressure. In some patients it causes a higher blood pressure increase. [NIH]

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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] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Compounds: Inorganic compounds that contain silicon as an integral part of the molecule. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [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] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sludge: A clump of agglutinated red blood cells. [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 Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [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] Sodium Fluoride: A source of inorganic fluoride which is used topically to prevent dental caries. [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] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of

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dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] 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] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] 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] Spotting: A slight discharge of blood via the vagina, especially as a side-effect of oral contraceptives. [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]

Steady state: Dynamic equilibrium. [EU]

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Steatorrhea: A condition in which the body cannot absorb fat. Causes a buildup of fat in the stool and loose, greasy, and foul bowel movements. [NIH] Steatosis: Fatty degeneration. [EU] Stellate: Star shaped. [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] Stomachic: Medicine that acts like a tonic on the stomach. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH]

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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] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [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] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Swainsonine: An indolizidine alkaloid from the plant Swainsona canescens that is a potent alpha-mannosidase inhibitor. Swainsonine also exhibits antimetastatic, antiproliferative, and immunomodulatory activity. [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] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] 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] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] 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]

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Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] Tenotomy: The cutting of a tendon. [NIH] Teratogenesis: Production of monstrous growths or fetuses. [NIH] Teratoma: A type of germ cell tumor that may contain several different types of tissue, such as hair, muscle, and bone. Teratomas occur most often in the ovaries in women, the testicles in men, and the tailbone in children. Not all teratomas are malignant. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [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] 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]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment

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of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] 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] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tibial Nerve: The medial terminal branch of the sciatic nerve. The tibial nerve fibers originate in lumbar and sacral spinal segments (L4 to S2). They supply motor and sensory innervation to parts of the calf and foot. [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 Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] 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

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pregnancy. [EU] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] 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] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transversion: A base-pair substitution mutation in which a purine-pyrimidine pair is replaced by the equivalent pyrimidine-purine pair, i. e. A-T becomes T-A. [NIH]

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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] Tributyrin: A triglyceride drug that may inhibit cell growth and induce cell differentiation. Differentiating agents may be effective in changing cancer cells back into normal cells. [NIH] 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] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] 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] 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] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tunicamycin: An N-acetylglycosamine containing antiviral antibiotic obtained from Streptomyces lysosuperificus. It is also active against some bacteria and fungi, because it inhibits the glucosylation of proteins. Tunicamycin is used as tool in the study of microbial biosynthetic mechanisms. [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] 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] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unsaturated Fats: A type of fat. [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

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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] 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] 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] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

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] 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] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body 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] 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]

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Ventricular: Pertaining to a ventricle. [EU] Vertebrae: A bony unit of the segmented spinal column. [NIH] Very low-density lipoprotein: The lipoprotein particles that initially leave the liver, carrying cholesterol and lipid. VLDLs contain 10 to 15 percent of the total serum cholesterol along with most of the triglycerides in the fasting serum; VLDLs are precursors of LDL, and some forms of VLDL, particularly VLDL remnants, appear to be atherogenic. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] Villus: Cell found in the lining of the small intestine. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [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] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral fat: One of the three compartments of abdominal fat. Retroperitoneal and subcutaneous are the other two compartments. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitellogenin: A serum and yolk protein which has been characterized as a calcium-binding glycolipophosphoprotein. It is induced by estrogen or juvenile hormone and is essential for yolk formation in various insect species. [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] Volition: Voluntary activity without external compulsion. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]

Waist circumference: To define the level at which the waist circumference is measured, a

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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] 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] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xanthine Oxidase: An iron-molybdenum flavoprotein containing FAD that oxidizes hypoxanthine, some other purines and pterins, and aldehydes. Deficiency of the enzyme, an autosomal recessive trait, causes xanthinuria. EC 1.1.3.22. [NIH] Xanthophyll: A carotenoid alcohol widespread in nature. It is present in egg yolk, algae, and petals of yellow flowers, among other sources. [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] 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]

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INDEX A Abdomen, 249, 259, 260, 276, 289, 293, 303, 304, 318, 319, 321, 326 Abdominal, 8, 16, 41, 50, 84, 120, 139, 249, 250, 263, 289, 290, 292, 302, 303, 304, 313, 326 Abdominal fat, 8, 16, 249, 263, 326 Abdominal Pain, 41, 139, 249, 290 Aberrant, 34, 55, 173, 221, 249 Acceptor, 57, 249, 292, 302, 323 ACE, 194, 249 Acetone, 202, 249, 291 Acetylcholine, 43, 249, 264, 300 Acetylcholinesterase, 43, 249, 271 Acetyltransferases, 36, 249 Acne, 159, 186, 249 Actin, 6, 47, 52, 249, 280, 298, 299 Acute renal, 21, 249 Acyl, 25, 39, 101, 127, 172, 173, 197, 199, 249, 276, 294, 295, 306 Acylation, 47, 143, 188, 199, 249 Adaptation, 134, 151, 249 Adenosine, 249, 253, 260, 287, 306 Adenovirus, 14, 33, 250 Adjustment, 249, 250 Adjuvant, 250, 280 Adrenal Cortex, 250, 269, 285, 309, 313 Adrenal Glands, 250, 313 Adrenal insufficiency, 13, 250 Adrenal Medulla, 250, 262, 276, 300 Adrenaline, 91, 250 Adrenergic, 15, 24, 44, 48, 86, 96, 250, 255, 273, 276, 320 Adrenergic Agents, 44, 250 Adrenergic beta-Antagonists, 250, 255 Adsorption, 35, 174, 175, 250 Adsorptive, 250 Adverse Effect, 190, 250, 317 Aerobic, 16, 164, 250, 251, 260, 296, 311 Aerobic Exercise, 164, 250 Aetiology, 90, 250 Afferent, 13, 250, 291 Affinity, 14, 26, 27, 33, 67, 89, 155, 251, 257, 292, 317 Aflatoxins, 188, 251 Agar, 251, 307 Age of Onset, 251, 324 Agonist, 43, 49, 251, 271, 273

Alanine, 218, 251 Albumin, 18, 251, 307 Alcaligenes, 65, 201, 251 Alcohol Dehydrogenase, 5, 251 Aldehydes, 251, 327 Alertness, 251, 260 Algorithms, 251, 259 Alimentary, 106, 138, 200, 212, 252, 272 Alkaline, 73, 134, 187, 189, 218, 252, 253, 260, 305 Alkaline Phosphatase, 218, 252 Alkaloid, 252, 258, 261, 320 Alleles, 5, 65, 252, 284, 292 Allopurinol, 127, 252 Alloys, 252, 265, 302 Allylamine, 252 Alpha Particles, 252, 312 Alpha-1, 252, 273, 306 Alpha-Amylase, 104, 156, 206, 252 Alpha-Linolenic Acid, 145, 252 Alternative medicine, 225, 252 Ameliorating, 172, 212, 214, 252 Amine, 199, 252, 285 Amino Acid Substitution, 126, 253 Amino-terminal, 212, 253 Amiodarone, 91, 253 Amlodipine, 24, 253 Ammonia, 252, 253, 324 Amylase, 41, 79, 90, 118, 119, 121, 187, 192, 206, 218, 253, 303 Amyloid, 20, 253 Amylopectin, 253, 290 Anaesthesia, 253, 288 Anal, 65, 190, 253, 278, 301 Analgesic, 253, 287 Analog, 59, 253, 265 Analogous, 56, 253, 273, 323 Anaphylatoxins, 253, 266 Anatomical, 253, 287, 293, 296 Anemia, 253, 265, 304 Anesthetics, 253, 276 Angina, 250, 253, 254 Angina Pectoris, 250, 253, 254 Angiotensin-Converting Enzyme Inhibitors, 254, 255 Angiotensinogen, 24, 254, 313 Anhydrous, 176, 254

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Animal model, 5, 9, 19, 29, 30, 32, 180, 221, 254 Anionic, 176, 187, 254 Anions, 251, 254, 290, 316, 320 Annealing, 254, 308 Anorexia, 172, 254, 324 Antagonism, 254, 260 Anthracycline, 6, 254, 270 Antianginal, 253, 254 Antiarrhythmic, 253, 254 Antibacterial, 38, 254, 265, 318 Antibiotic, 104, 254, 270, 273, 276, 292, 318, 321, 324 Antibodies, 7, 54, 173, 254, 255, 257, 283, 285, 287, 294, 297, 307 Antibody, 7, 25, 109, 251, 254, 255, 266, 276, 283, 285, 287, 288, 295, 297, 318 Anticoagulant, 254, 310 Antigen, 7, 18, 251, 254, 255, 266, 276, 285, 287, 288, 295, 296 Antigen-Antibody Complex, 255, 266 Antigen-presenting cell, 18, 255 Antihypertensive, 15, 24, 255 Antihypertensive Agents, 24, 255 Anti-infective, 255, 279, 286, 317 Anti-Infective Agents, 255, 279 Anti-inflammatory, 5, 255, 281, 287, 288, 303 Antimetabolite, 255, 296 Antimetastatic, 255, 320 Antimicrobial, 135, 156, 255, 271 Antineoplastic, 255, 273, 296 Antioxidant, 202, 255, 256, 280, 302 Antiproliferative, 255, 320 Antipruritic, 255, 264 Antiseptic, 249, 255 Antiserum, 196, 255 Antiviral, 60, 255, 324 Anus, 253, 255, 260, 266 Apolipoproteins, 12, 62, 71, 91, 205, 255, 292 Apolipoproteins A, 12, 255 Aqueous, 58, 141, 172, 175, 177, 183, 185, 201, 214, 256, 269, 274, 286, 293 Arachidonate 12-Lipoxygenase, 256, 293 Arachidonate 15-Lipoxygenase, 256, 293 Arachidonate Lipoxygenases, 256, 293 Arachidonic Acid, 6, 34, 135, 142, 146, 150, 155, 256, 274, 310 Arginine, 253, 256, 285, 300, 324 Arterial, 9, 24, 205, 252, 256, 260, 264, 268, 286, 310, 320

Arteries, 103, 256, 257, 259, 269, 293, 296, 298, 321 Arteriosclerosis, 79, 89, 92, 95, 96, 109, 110, 111, 114, 138, 154, 256, 286, 298 Artery, 6, 22, 23, 40, 42, 67, 79, 85, 88, 97, 98, 99, 103, 106, 107, 256, 269, 311, 315 Ascorbic Acid, 204, 256, 286 Aseptic, 256, 319 Aspartate, 218, 256 Aspartic, 196, 218, 256, 275 Aspartic Acid, 256 Assay, 62, 94, 95, 99, 133, 134, 147, 190, 257, 287 Astringents, 257, 295 Astrocytes, 34, 257, 284, 294, 296 Asymptomatic, 257, 303 Atherogenic, 10, 33, 58, 101, 257, 326 Atmospheric Pressure, 185, 257 Atrial, 253, 257, 268, 320 Atrophy, 257, 292 Attenuated, 15, 257, 325 Autoantibodies, 7, 257 Autoantigens, 257 Autodigestion, 257, 303 Autologous, 18, 257 Autonomic, 249, 257, 280, 300, 304 Avian, 150, 257 Axilla, 135, 257 B Backcross, 21, 257 Bacterial Physiology, 249, 257 Bactericidal, 7, 257, 277 Bacteriophage, 71, 257, 307, 323 Bacteriostatic, 257, 276 Bacterium, 67, 72, 73, 257, 267 Base Sequence, 189, 258, 281 Basement Membrane, 258, 277 Basophils, 258, 283, 291 Behavior Therapy, 9, 258 Berberine, 146, 258 Beta-pleated, 253, 258 Bile Acids, 177, 179, 197, 207, 213, 258, 319, 320 Bile Acids and Salts, 258 Bile duct, 258 Biliary, 217, 258, 261, 264, 284, 303 Biliary Tract, 258, 261, 303 Bilirubin, 251, 258 Binding agent, 190, 258 Bioavailability, 157, 258 Biochemical reactions, 39, 258 Biological therapy, 258, 283

331

Biological Transport, 258, 272 Biomass, 184, 201, 258 Biosynthesis, 38, 39, 51, 136, 164, 256, 259, 293, 310, 316, 317 Biotransformation, 201, 259 Bladder, 106, 259, 279, 288, 325 Blastocyst, 259, 267, 307 Bloating, 182, 259, 288, 290 Blood Coagulation, 259, 260, 321 Blood Glucose, 259, 289 Blood Platelets, 259, 316 Blood pressure, 15, 24, 107, 116, 122, 247, 255, 259, 262, 280, 286, 297, 300, 316, 317 Blood Volume, 259, 262 Body Composition, 8, 36, 47, 58, 259 Body Fluids, 259, 273, 279, 301, 317 Body Mass Index, 3, 35, 48, 104, 111, 259, 302 Bone Marrow, 33, 51, 259, 281, 287, 293, 294, 317, 319 Bone scan, 259, 315 Boronic Acids, 209, 260 Bowel, 253, 260, 288, 289, 301, 304, 319 Bowel Movement, 260, 319 Bradykinin, 260, 300, 307 Brain Infarction, 80, 260 Brain Stem, 260, 264, 299 Brain Stem Infarctions, 260 Breast Feeding, 118, 260 Bronchi, 260, 276, 323 Bronchial, 260, 285 Buccal, 260, 293 Burkholderia, 128, 174, 260 C Caffeine, 218, 260, 312 Calcium, 20, 30, 38, 115, 137, 152, 187, 202, 253, 255, 260, 261, 266, 280, 289, 326 Calcium Carbonate, 187, 260 Calcium channel blocker, 253, 255, 260 Calcium Channel Blockers, 255, 261 Calcium Channels, 30, 261 Calculi, 261, 283 Calibration, 86, 261 Calmodulin, 152, 261, 289 Caloric intake, 180, 221, 261 Capillary, 260, 261, 292 Capping, 52, 261 Capsaicin, 140, 261 Capsules, 261, 275, 280 Carbohydrate, 5, 58, 138, 207, 261, 282, 283, 301, 308, 316

Carbon Dioxide, 203, 261, 270, 280, 307, 313, 325 Carboxy, 261 Carboxylic Acids, 211, 261 Carcinogenic, 261, 288, 309, 319 Carcinogens, 261, 302 Carcinoma, 78, 261, 262 Cardiac, 6, 15, 49, 68, 141, 144, 250, 252, 254, 260, 262, 268, 269, 276, 280, 282, 298, 319 Cardiomyopathy, 6, 69, 80, 262 Cardiorespiratory, 250, 262 Cardiovascular Agents, 194, 262 Carotene, 191, 262, 314 Carotenoids, 191, 202, 203, 262 Case report, 119, 262 Castor Oil, 262, 314 Catabolism, 22, 25, 62, 82, 90, 101, 262 Catalyse, 176, 190, 262 Catalytic Domain, 35, 262 Catecholamine, 48, 262, 271, 272, 305 Cations, 262, 290 Caudal, 262, 271, 286, 308 Causal, 6, 22, 50, 262 Cause of Death, 45, 205, 262 Caustic, 262, 317 Cecum, 262, 291 Celiac Disease, 52, 159, 262 Cell Death, 263, 298 Cell Differentiation, 13, 42, 263, 324 Cell Division, 257, 263, 269, 283, 307, 316 Cell membrane, 173, 258, 261, 263, 271, 289, 290, 306, 326 Cell motility, 52, 263 Cell Physiology, 52, 263 Cell proliferation, 11, 256, 263 Cell Respiration, 263, 296, 313 Cell Size, 79, 263 Cell Survival, 263, 283 Cellulose, 263, 279, 307 Central fat distribution, 13, 263 Central Nervous System, 13, 249, 251, 260, 261, 263, 274, 280, 282, 284, 296, 316 Centrifugation, 263, 296 Ceramide, 81, 263, 282 Cerebellum, 260, 263 Cerebral, 45, 84, 107, 260, 264, 268, 276, 277, 298, 303 Cerebral hemispheres, 260, 264 Cerebrovascular, 6, 126, 261, 262, 264 Cerebrum, 264 Ceroid, 264, 292

332

Lipase

Character, 210, 254, 264, 270, 282 Chemical Warfare, 43, 264 Chemotactic Factors, 264, 266 Chemotaxis, 72, 264 Chlorella, 202, 264 Chlorophyll, 64, 264, 279 Chlorpyrifos, 43, 264 Cholesterol Esterase, 99, 264 Cholesterol Esters, 205, 264, 292 Cholestyramine, 142, 264 Choline, 173, 249, 264 Cholinergic, 96, 264 Chondrocytes, 264, 278 Chromatin, 36, 265, 276, 300, 318 Chromosomal, 21, 27, 71, 265, 285, 314, 315 Chromosome, 21, 27, 116, 265, 267, 283, 292, 315, 316 Chronic, 4, 25, 41, 60, 74, 104, 172, 214, 218, 255, 265, 266, 286, 288, 303, 319, 324 Chronic Disease, 4, 214, 265, 266 Chylomicrons, 32, 48, 70, 144, 148, 157, 173, 205, 213, 265, 292 Cirrhosis, 21, 265 CIS, 10, 64, 85, 133, 201, 265, 314 Cleave, 211, 261, 265 Clindamycin, 65, 265 Clinical Medicine, 265, 309 Clinical trial, 4, 10, 21, 24, 42, 48, 233, 265, 268, 273, 311, 312 Cloning, 38, 40, 60, 64, 67, 71, 72, 73, 86, 111, 147, 154, 259, 265 Clot Retraction, 265, 307 Cobalt, 172, 265 Coculture, 69, 265 Codon, 61, 265, 281 Coenzyme, 249, 256, 265, 293, 317 Cofactor, 34, 69, 102, 265, 310, 321 Cognition, 13, 265 Coliphages, 257, 266 Colitis, 266, 288, 290 Collagen, 54, 252, 258, 266, 278, 280, 285, 307, 309 Collagen disease, 266, 285 Colloidal, 251, 266, 274, 305, 316 Colon, 11, 52, 53, 190, 266, 288, 290, 291 Colostrum, 168, 266 Combinatorial, 128, 266 Communis, 262, 266, 314 Complement, 7, 40, 253, 266, 267, 281, 294, 307

Complementary and alternative medicine, 133, 161, 266 Complementary medicine, 133, 267 Computational Biology, 233, 267 Computed tomography, 16, 267, 315 Computerized axial tomography, 267, 315 Computerized tomography, 267 Conception, 267, 278, 319 Concomitant, 9, 38, 267 Cones, 267, 314 Confidence Intervals, 21, 267 Confounding, 22, 36, 267 Congestive heart failure, 194, 267, 293 Conjugated, 47, 136, 148, 155, 258, 267 Conjugation, 259, 267 Connective Tissue, 18, 256, 259, 266, 268, 278, 280, 293, 311, 314, 321 Connective Tissue Cells, 268 Consciousness, 253, 268, 270, 272, 311 Constipation, 268, 290, 316 Constitutional, 5, 32, 268 Constriction, 268, 290, 315, 325 Contractility, 6, 254, 268 Contraindications, ii, 268 Contrast medium, 268, 269 Control group, 45, 268 Conventional therapy, 268 Conventional treatment, 21, 268 Convulsions, 268, 274, 309 Cor, 268, 310 Corn Oil, 136, 138, 149, 268 Coronary Angiography, 87, 269 Coronary Disease, 5, 224, 269 Coronary heart disease, 4, 13, 19, 24, 45, 92, 262, 263, 269 Coronary Thrombosis, 269, 296, 298 Coronary Vessels, 269 Cortex, 269, 275, 277, 298 Cortical, 41, 269, 277 Cortisol, 13, 59, 251, 269 Creatinine, 218, 269, 324 Crossing-over, 269, 312 Crystallization, 66, 169, 269 Cultured cells, 45, 269 Curative, 269, 300, 314, 321 Cutaneous, 84, 269, 293 Cyclic, 61, 62, 68, 202, 260, 261, 269, 283, 300, 306 Cysteine, 34, 183, 269, 275 Cystine, 34, 269 Cytogenetics, 152, 269, 315 Cytokine, 29, 42, 51, 269, 304

333

Cytoplasm, 258, 263, 269, 274, 275, 276, 283, 289, 298, 299, 300, 314 Cytoskeleton, 47, 52, 269, 296 Cytotoxic, 108, 261, 270 Cytotoxicity, 145, 252, 270 D Dairy Products, 270, 310, 315 Daunorubicin, 270, 273 De novo, 46, 270 Deamination, 270, 325 Decarboxylation, 270, 285 Decidua, 270, 307 Decubitus, 169, 270 Decubitus Ulcer, 169, 270 Defecation, 178, 270 Degenerative, 270, 284, 294 Deletion, 19, 24, 42, 61, 71, 270 Dementia, 270, 299 Denaturation, 270, 308 Dendrites, 270, 271, 299 Density, 21, 22, 24, 25, 27, 31, 32, 45, 48, 51, 59, 60, 63, 66, 67, 68, 70, 72, 74, 75, 79, 80, 82, 88, 89, 90, 91, 92, 93, 94, 97, 100, 101, 102, 106, 120, 121, 149, 156, 173, 205, 255, 259, 263, 270, 273, 292, 301, 308 Dental Caries, 270, 317 Dentate Gyrus, 270, 284 Deoxyribonucleic, 271, 314 Depolarization, 146, 271 Deprivation, 95, 271 Dermal, 169, 271 Dermatitis, 168, 169, 271 Detergents, 176, 177, 179, 183, 185, 186, 187, 189, 197, 198, 199, 207, 271, 278 Deuterium, 271, 285 Developed Countries, 208, 271, 279 Developing Countries, 214, 271 Dexfenfluramine, 8, 271 Diabetes Mellitus, 32, 215, 271, 281 Diabetic Ketoacidosis, 118, 271 Diagnostic procedure, 167, 225, 271 Dialyzer, 271, 284 Diarrhea, 214, 264, 271, 290 Diastolic, 271, 286 Diathesis, 20, 271 Diazinon, 43, 271 Dichlorvos, 127, 271 Diencephalon, 271, 286, 299 Dietary Fats, 57, 147, 157, 177, 179, 194, 197, 207, 272 Dietary Fiber, 140, 142, 158, 178, 272 Diffusion, 54, 55, 173, 258, 272, 290

Digestive tract, 172, 192, 213, 272, 317 Dihydrotestosterone, 272, 313 Dimerization, 17, 84, 110, 272 Diploid, 272, 307 Direct, iii, 30, 48, 57, 63, 65, 88, 89, 227, 265, 272, 273, 313, 320 Disaccharides, 207, 272 Discrete, 40, 272, 321 Disease Vectors, 272, 289 Disinfectant, 272, 277 Dissociation, 116, 251, 272 Dissociative Disorders, 272 Distal, 31, 177, 179, 207, 272, 304, 309 Diuresis, 260, 272 Diuretics, Thiazide, 255, 272 Docosahexaenoic Acids, 142, 158, 272 Dopamine, 272, 300, 305 Dose-dependent, 35, 81, 90, 273 Double-blind, 113, 273 Doxazosin, 24, 273 Doxorubicin, 6, 273 Drive, ii, vi, 9, 54, 125, 217, 273, 290 Drug Design, 23, 273 Drug Interactions, 228, 273 Drug Tolerance, 273, 322 Duct, 273, 277, 302, 315 Duodenal Ulcer, 38, 273 Duodenum, 57, 192, 258, 273, 280, 303, 319 Dyes, 253, 258, 273, 279, 300, 305 Dyslipidemia, 4, 13, 32, 87, 96, 99, 102, 123, 263, 273 Dyspepsia, 181, 273, 288 Dystrophic, 20, 273 Dystrophy, 40, 273 E Eclampsia, 274, 309 Edema, 274, 299, 309, 324 Effector, 13, 15, 74, 249, 266, 274, 299, 305 Effector cell, 74, 274, 299 Efferent, 13, 274 Efficacy, 6, 20, 32, 41, 42, 51, 123, 180, 224, 273, 274 Egg Yolk, 274, 327 Eicosanoids, 5, 274 Elastic, 274, 282, 320 Elastin, 266, 274 Elective, 75, 274 Electrolyte, 274, 279, 301, 308, 317, 324 Electrons, 255, 274, 290, 302, 312 Electrophoresis, 51, 54, 274 Embryo, 157, 259, 263, 274, 288 Emollient, 274, 282, 301

334

Lipase

Emulsify, 187, 274 Emulsion, 37, 168, 169, 190, 201, 274 Endocytosis, 10, 20, 52, 59, 275 Endogenous, 11, 13, 30, 31, 34, 41, 52, 59, 69, 145, 205, 257, 272, 274, 275, 302, 310, 323 Endopeptidases, 275, 304, 310 Endorphins, 275, 300, 310 Endothelial cell, 17, 26, 30, 33, 50, 63, 69, 76, 103, 108, 205, 275, 278, 321 Endothelium, 275, 300, 307 Endothelium-derived, 275, 300 Endotoxic, 275, 292 Endotoxins, 266, 275, 291 Energy balance, 36, 275, 291 Energy deficit, 16, 275 Energy Intake, 275 Enhancer, 19, 44, 168, 275 Enkephalin, 275, 310 Enteric-coated, 151, 275 Enterohepatic, 178, 179, 207, 275 Enteropeptidase, 275, 324 Entorhinal Cortex, 275, 285 Environmental Exposure, 12, 275 Environmental Health, 28, 232, 234, 275 Enzyme Activators, 54, 276 Enzyme-Linked Immunosorbent Assay, 65, 88, 276 Eosinophils, 276, 283, 291 Epidemic, 4, 44, 276 Epidemiological, 28, 276 Epigastric, 276, 302 Epinephrine, 53, 74, 250, 272, 276, 300, 324 Epithelial, 52, 55, 129, 155, 205, 217, 258, 270, 276, 297 Epithelial Cells, 205, 217, 276, 297 Epithelium, 151, 258, 275, 276, 280, 290 Epitope, 109, 276 Erythrocytes, 253, 259, 276, 313 Erythromycin, 65, 276 Esophagus, 272, 276, 284, 319 Esterification, 39, 53, 143, 144, 169, 170, 172, 174, 176, 193, 276 Estrogen, 75, 277, 309, 326 Ethanol, 127, 176, 202, 251, 277, 278 Ethanolamine, 173, 277 Ethnic Groups, 95, 277 Eukaryotic Cells, 277, 287, 301, 324 Euphorbiaceae, 69, 277 Evacuation, 268, 277, 280 Evoke, 277, 319 Excipients, 277, 279, 305

Excitation, 277, 300 Excitatory, 34, 41, 277, 282 Excitotoxicity, 34, 277 Exocrine, 69, 171, 217, 277, 302, 303 Exogenous, 11, 46, 59, 61, 76, 250, 259, 275, 277, 310, 324 Exon, 19, 61, 65, 71, 110, 112, 277 Extracellular Matrix, 54, 70, 115, 268, 277, 278 Extracellular Space, 277 Extraction, 147, 201, 202, 203, 277 Extremity, 277, 315 Exudate, 70, 277 Eye Infections, 250, 278 F Family Planning, 233, 278 Fat Body, 38, 278 Fat Necrosis, 78, 278 Fatigue, 278, 284 Fatty Liver, 40, 278 Fecal Incontinence, 178, 190, 278, 288, 301 Feces, 169, 178, 268, 278, 319 Fenfluramine, 8, 271, 278 Fermentation, 65, 142, 147, 183, 184, 251, 278, 279 Fetus, 278, 307, 309, 325 Fibrinogen, 12, 278, 307, 321 Fibrinolytic, 51, 278 Fibroblast Growth Factor, 135, 278 Fibroblasts, 18, 63, 268, 278, 289 Fibrosis, 41, 54, 69, 93, 94, 117, 138, 152, 159, 252, 278 Fish Oils, 143, 148, 169, 272, 278 Flatus, 278, 280 Flavoring Agents, 279, 305 Fluid Therapy, 279, 301 Fluorescence, 30, 58, 116, 121, 279 Fluoxetine, 91, 279 Foam Cells, 33, 42, 70, 279 Fold, 6, 31, 164, 279 Food Additives, 185, 279 Food Coloring Agents, 279 Food Preservatives, 279 Forearm, 119, 259, 279 Free Radicals, 6, 50, 255, 272, 279 Freeze Drying, 172, 279 Freeze-dried, 53, 279 Fundus, 212, 279 Fungi, 185, 267, 278, 279, 280, 296, 298, 324, 325, 327 Fungus, 181, 183, 279

335

G Gallate, 152, 280 Gallbladder, 159, 218, 249, 258, 279, 280 Ganglia, 249, 260, 280, 299, 304 Ganglionic Blockers, 255, 280 Gas, 253, 261, 272, 277, 278, 280, 285, 288, 290, 300, 325 Gas exchange, 280, 325 Gastric Acid, 218, 280, 304 Gastric Emptying, 117, 141, 172, 280 Gastric Inhibitory Polypeptide, 152, 280 Gastric Mucosa, 154, 280 Gastrin, 280, 285 Gastritis, 38, 280 Gastrointestinal tract, 175, 192, 214, 217, 277, 280, 316, 318 Gelatin, 51, 280, 282, 320, 321 Gelsolin, 52, 280 Gene Expression, 13, 16, 19, 23, 37, 42, 47, 50, 51, 58, 74, 102, 127, 129, 140, 280, 281 Gene Therapy, 118, 250, 280 Genetic Code, 281, 300 Genetic Engineering, 259, 265, 281 Genetic Markers, 23, 51, 281 Genetic Predisposition to Disease, 15, 281 Genetic testing, 281, 308 Genotype, 8, 24, 28, 32, 35, 47, 100, 101, 122, 281, 305 Germ Cells, 171, 281, 302, 318 Gestation, 281, 304, 307 Ginseng, 148, 161, 281 Gland, 111, 218, 250, 281, 293, 302, 304, 307, 316, 319, 322 Glomerular, 281, 313 Glucocorticoid, 10, 83, 281, 285 Glucose Intolerance, 46, 271, 281 Glucose tolerance, 16, 36, 120, 128, 281 Glucose Tolerance Test, 36, 281, 282 Glucosylceramidase, 15, 282 Glucuronic Acid, 282, 284 Glutamate, 34, 277, 282 Glutamic Acid, 196, 282, 300, 309 Gluten, 200, 204, 262, 282 Glycerol, 30, 41, 48, 99, 119, 168, 169, 173, 176, 181, 182, 189, 190, 200, 278, 282, 305, 306 Glycerophospholipids, 282, 306 Glyceryl Ethers, 173, 282 Glycine, 177, 179, 207, 252, 258, 282, 300, 316 Glycogen, 136, 252, 282, 290, 306 Glycogen Storage Disease, 136, 282

Glycolysis, 30, 282 Glycoprotein, 22, 171, 212, 278, 282, 290, 321, 324 Glycosaminoglycans, 282, 311 Glycoside, 272, 282, 286, 315 Glycosidic, 207, 252, 283, 301, 306 Glycosylation, 96, 99, 144, 196, 283 Glycosylceramidase, 16, 283 Gonadal, 283, 319 Gout, 20, 87, 283 Governing Board, 283, 309 Grade, 264, 283 Gram-negative, 38, 251, 260, 275, 283, 311 Gram-positive, 77, 283, 310 Gram-Positive Bacteria, 77, 283 Granulocytes, 74, 283, 327 Growth factors, 129, 168, 283, 296, 299 Guanylate Cyclase, 283, 300 H Habitual, 264, 283 Haploid, 283, 307 Haplotypes, 45, 48, 88, 283 Haptens, 251, 283 Headache, 260, 284, 316 Heart attack, 262, 284 Heart failure, 24, 254, 284 Heartburn, 172, 218, 284, 288 Hemodialysis, 83, 100, 107, 115, 260, 271, 284 Hemorrhage, 284, 314, 319 Hemostasis, 33, 284, 316 Heparan Sulfate Proteoglycan, 17, 284 Heparin, 33, 66, 67, 69, 90, 92, 95, 96, 107, 110, 113, 116, 129, 141, 155, 284 Hepatitis, 122, 284 Hepatobiliary, 218, 284 Hepatocyte, 18, 60, 84, 284 Hepatoma, 110, 284 Hereditary, 283, 284, 305 Heredity, 280, 281, 284 Heterogeneity, 251, 284 Heterotrophic, 279, 284 Heterozygotes, 35, 75, 284 Hippocampus, 41, 270, 284, 299, 319 Histamine, 172, 253, 285 Histidine, 196, 285 Histology, 285, 299, 303 Histones, 265, 285 Homeostasis, 4, 5, 7, 11, 19, 29, 34, 35, 37, 46, 52, 55, 59, 209, 285 Homogeneous, 36, 187, 190, 285

336

Lipase

Homologous, 25, 40, 68, 198, 213, 252, 269, 281, 284, 285, 316, 320 Hormonal, 28, 44, 68, 190, 257, 285, 304, 326 Horseradish Peroxidase, 276, 285 Human Development, 28, 232, 285 Hybrid, 257, 285 Hybridomas, 285, 289 Hydrochloric Acid, 202, 285 Hydrocortisone, 13, 285 Hydrogel, 53, 285 Hydrogen, 215, 249, 251, 252, 261, 270, 271, 285, 286, 292, 297, 300, 302, 311, 320 Hydrogen Peroxide, 286, 292, 320 Hydrolases, 54, 286, 306 Hydrophobic, 29, 172, 174, 213, 271, 282, 286, 292 Hydroxylysine, 266, 286 Hydroxyproline, 252, 266, 286 Hypercholesterolemia, 111, 114, 179, 273, 286 Hyperglycemia, 4, 9, 10, 56, 181, 286 Hyperlipoproteinemia, 65, 66, 75, 126, 286, 292 Hypertension, Renal, 15, 286 Hypertension, Renovascular, 286 Hyperthyroidism, 18, 286 Hypertriglyceridemia, 7, 31, 61, 62, 75, 76, 92, 102, 114, 151, 273, 286 Hypertrophy, 15, 24, 75, 268, 286 Hyperuricemia, 283, 286 Hypothalamic, 13, 286 Hypothalamus, 13, 271, 275, 286, 307, 310, 318 Hypothyroidism, 53, 286 Hypoxanthine, 287, 327 I Ibuprofen, 53, 287 Ice Cream, 194, 287 Ileum, 177, 179, 207, 262, 287, 327 Immune function, 33, 287 Immune response, 7, 18, 250, 255, 257, 283, 287, 294, 320, 326 Immune Sera, 287 Immune system, 38, 255, 258, 274, 287, 294, 305, 327 Immunization, 7, 287 Immunoassay, 116, 276, 287 Immunofluorescence, 54, 287 Immunogenic, 287, 292 Immunoglobulin, 192, 254, 287, 297 Immunologic, 264, 287, 303

Immunology, 56, 108, 122, 250, 251, 285, 287 Immunosuppressant, 287, 296 Immunosuppressive, 281, 287 Impairment, 121, 278, 287, 294 In situ, 29, 57, 152, 193, 199, 287 In Situ Hybridization, 152, 287 Incision, 288, 290 Incontinence, 288 Incubated, 57, 288 Indigestion, 218, 288 Indomethacin, 127, 288 Induction, 18, 53, 64, 85, 164, 280, 288, 309, 317 Infancy, 93, 288, 314 Infantile, 288, 292 Infarction, 260, 288 Inflammatory bowel disease, 52, 288 Infusion, 107, 288 Ingestion, 99, 181, 282, 288, 308 Inhalation, 288, 308 Initiation, 36, 288, 323 Innervation, 288, 305, 315, 322 Inorganic, 170, 183, 187, 260, 288, 290, 298, 305, 317 Inositol, 134, 288, 289 Inositol 1,4,5-Trisphosphate, 134, 289 Insecticides, 43, 289, 305 Insight, 5, 13, 26, 31, 37, 42, 289 Insomnia, 289, 316 Insulin-dependent diabetes mellitus, 48, 181, 289 Insulin-like, 9, 289 Interindividual, 23, 289 Interleukin-1, 74, 289 Interleukin-2, 289 Interleukin-6, 84, 289 Intermediate Filaments, 289, 299 Interstitial, 277, 289, 313 Intestinal Mucosa, 134, 192, 262, 289 Intraperitoneal, 43, 289 Intravascular, 37, 289 Intravenous, 3, 37, 288, 290 Intrinsic, 218, 251, 258, 290 Intrinsic Factor, 218, 290 Invasive, 7, 14, 50, 290, 294 Involuntary, 58, 278, 290, 298 Iodates, 204, 290 Ion Channels, 41, 257, 290 Ion Transport, 52, 290 Ionizing, 252, 275, 290

337

Ions, 187, 261, 264, 272, 274, 280, 285, 289, 290, 291, 297 Iris, 155, 290 Irritable Bowel Syndrome, 290, 301 Ischemia, 257, 270, 290 Islet, 30, 290 Isoamylase, 79, 290 Isoelectric, 191, 290 Isoelectric Point, 191, 290 Isoenzymes, 154, 291 Isopropyl, 210, 291 K Kb, 28, 232, 291 Keto, 188, 291 Ketoacidosis, 249, 291 Ketone Bodies, 249, 271, 291 Ketosis, 271, 291 Kinetic, 105, 140, 147, 195, 199, 290, 291 L Labile, 266, 291 Lactation, 263, 266, 291, 309 Large Intestine, 177, 179, 207, 262, 272, 289, 291, 312, 317 Latent, 59, 281, 291, 309 Leptin, 5, 21, 27, 29, 47, 58, 106, 291 Lesion, 9, 42, 115, 291, 293, 324 Lethal, 31, 257, 291, 314 Lethargy, 286, 291 Leukemia, 65, 273, 281, 291 Leukocytes, 135, 258, 259, 264, 276, 283, 288, 291, 300, 305, 324 Life cycle, 250, 279, 291 Ligaments, 269, 291 Ligands, 10, 14, 20, 23, 31, 41, 49, 52, 291 Ligation, 12, 291 Lincomycin, 65, 265, 292 Linkage, 15, 27, 29, 40, 47, 107, 112, 261, 281, 282, 292, 305 Linkage Disequilibrium, 15, 28, 292 Lip, 39, 145, 292 Lipaemia, 92, 292 Lipid A, 5, 6, 10, 25, 31, 35, 37, 38, 40, 42, 60, 122, 156, 194, 263, 292, 301 Lipid Peroxidation, 6, 32, 55, 292, 302 Lipodystrophy, 50, 292 Lipofuscin, 55, 264, 292 Lipophilic, 91, 190, 214, 292 Lipopolysaccharide, 38, 69, 74, 139, 283, 292 Lipoprotein(a), 12, 65, 292 Liposomes, 55, 292 Lipoxygenase, 5, 178, 256, 293

Liquor, 202, 293 Lisinopril, 24, 293 Liver scan, 293, 315 Lobe, 293, 310 Localization, 47, 56, 71, 103, 152, 163, 197, 293 Localized, 55, 270, 288, 292, 293, 307, 324 Locomotion, 293, 307 Loop, 13, 59, 102, 129, 293 Lovastatin, 293, 317 Low-density lipoprotein, 20, 42, 79, 122, 154, 273, 292, 293 Lumbar, 293, 315, 322 Lupus, 6, 266, 293 Lutein Cells, 293, 309 Lymph, 213, 275, 293, 294 Lymph node, 293, 294 Lymphatic, 48, 275, 288, 293, 307, 317, 318, 322 Lymphatic system, 48, 293, 317, 318, 322 Lymphocyte, 255, 294, 295 Lymphoid, 254, 294 Lysine, 183, 285, 286, 294, 324 Lysophospholipase, 11, 43, 47, 145, 149, 154, 163, 294 Lysophospholipids, 11, 294 Lytic, 7, 294, 316 M Macroglia, 294, 296 Macrophage, 5, 9, 16, 42, 57, 70, 109, 121, 139, 289, 294 Macula, 294 Macula Lutea, 294 Macular Degeneration, 55, 294 Magnetic Resonance Imaging, 294, 315 Major Histocompatibility Complex, 283, 294 Malabsorption, 41, 159, 197, 262, 294 Malabsorption Syndromes, 159, 197, 294 Malignant, 255, 294, 298, 321 Malnutrition, 218, 251, 257, 294 Mammary, 49, 74, 111, 151, 171, 266, 292, 294 Mannans, 279, 294 Marijuana Abuse, 41, 294 Meat, 272, 294, 295, 315 Meat Products, 272, 295 Mediate, 50, 58, 273, 295 Mediator, 70, 74, 289, 295, 316 MEDLINE, 233, 295 Melanin, 290, 295, 305, 324 Membrane Fluidity, 55, 57, 295

338

Lipase

Membrane Lipids, 295, 306 Membrane Proteins, 292, 295 Memory, 254, 270, 295 Meninges, 263, 295 Menopause, 36, 295, 308 Menstruation, 270, 295 Mental, iv, 4, 232, 234, 265, 270, 272, 278, 286, 295, 311, 316, 324, 325 Mental Processes, 272, 295, 311 Menthol, 210, 295 Mercury, 34, 295 Metabolic acidosis, 271, 295 Metabolic disorder, 31, 282, 283, 295 Metabolite, 150, 259, 293, 296, 309 Metastasis, 52, 296 Methionine, 296, 310 Methotrexate, 21, 296 MI, 4, 12, 45, 92, 97, 112, 206, 218, 248, 296 Micelle, 197, 205, 296 Microbe, 296, 323 Microbiology, 38, 118, 122, 135, 136, 137, 138, 144, 145, 149, 151, 153, 249, 296 Microglia, 20, 257, 296 Microorganism, 265, 296, 303, 326 Microsomal, 45, 296 Microtubule-Associated Proteins, 296, 299 Microtubules, 289, 296, 299 Midaxillary line, 296, 327 Migration, 15, 172, 296 Millimeter, 296, 327 Mitochondria, 6, 46, 56, 71, 111, 296, 301 Mobility, 51, 98, 296 Mobilization, 17, 37, 213, 263, 296 Modeling, 59, 273, 297 Modification, 9, 34, 38, 59, 94, 154, 172, 193, 198, 224, 252, 281, 297, 312 Molecular mass, 11, 297 Molecular Structure, 129, 297 Monensin, 144, 297 Monitor, 51, 269, 297, 300 Monoclonal, 7, 33, 76, 109, 150, 285, 297 Monoclonal antibodies, 7, 33, 76, 150, 297 Monocyte, 9, 33, 70, 88, 89, 297 Mononuclear, 15, 297, 324 Monounsaturated fat, 176, 297 Morphological, 274, 279, 297 Morphology, 5, 297 Motility, 52, 280, 288, 297, 316 Motion Sickness, 297, 298 Motor Activity, 182, 268, 297 Mucosa, 11, 192, 212, 280, 293, 297, 309 Mucus, 218, 297

Muscular Dystrophies, 273, 298 Mutagenesis, 11, 58, 95, 118, 128, 164, 198, 298 Mutagens, 298 Mutate, 11, 298 Mycotoxins, 251, 298 Myelin, 32, 298 Myocardial infarction, 4, 12, 24, 45, 99, 104, 218, 269, 296, 298 Myocardial Ischemia, 254, 269, 298 Myocardium, 254, 296, 298 Myofibrils, 6, 298 Myopathy, 71, 111, 298 Myosin, 298 N Nausea, 182, 288, 291, 298, 324, 325 NCI, 1, 231, 265, 298 Necrosis, 260, 288, 296, 298, 316 Neocortex, 298, 299 Neonatal, 51, 75, 112, 150, 298 Neoplasia, 298, 299 Neoplasm, 298, 299 Neoplastic, 52, 285, 299 Nephropathy, 10, 15, 108, 299 Nephrosis, 299 Nephrotic, 6, 299 Nephrotic Syndrome, 6, 299 Nerve, 21, 32, 43, 103, 146, 250, 270, 274, 288, 295, 299, 304, 305, 314, 315, 319, 322, 323 Nerve Endings, 146, 299 Nerve Regeneration, 32, 299 Nervous System, 32, 251, 254, 263, 295, 299, 300, 304, 320, 325 Neural, 21, 41, 217, 250, 253, 280, 296, 299, 304 Neurites, 20, 299 Neuroeffector Junction, 299 Neurofibrillary Tangles, 20, 299 Neurofilaments, 299 Neuromuscular, 249, 299, 324 Neuromuscular Junction, 249, 299 Neuronal, 13, 20, 34, 41, 118, 261, 299 Neurons, 20, 34, 41, 270, 277, 280, 298, 299, 320 Neuropathy, 32, 43, 299, 304 Neurophysiology, 271, 300 Neurotoxicity, 34, 300 Neurotransmitter, 41, 249, 250, 252, 256, 260, 272, 282, 285, 290, 300, 318, 320 Neutrons, 252, 300, 312 Neutrophils, 256, 283, 291, 300

339

Niacin, 300, 324 Nitric Oxide, 205, 300 Nitrogen, 129, 184, 252, 297, 300, 303, 324 Norepinephrine, 250, 272, 300, 316 Normotensive, 140, 300 Nuclear, 20, 30, 36, 42, 51, 265, 267, 274, 277, 298, 300 Nucleic acid, 48, 173, 182, 183, 196, 204, 205, 211, 213, 258, 281, 287, 298, 300, 312, 314 Nucleotidases, 286, 300 Nucleus, 194, 258, 265, 269, 271, 276, 277, 289, 297, 300, 301, 311, 319 Nutritional Support, 37, 301 Nutritive Value, 279, 301 O Ointments, 169, 301, 303, 317 Oligo, 207, 301 Oligosaccharides, 129, 252, 301 Omega-3 fatty acid, 129, 145, 155, 301 Opacity, 270, 301 Operon, 62, 64, 73, 301, 313 Opportunistic Infections, 251, 301 Opsin, 301, 314 Optic Chiasm, 286, 301 Orbit, 18, 301 Orbital, 18, 266, 301 Organelles, 46, 57, 263, 269, 301, 307 Orlistat, 8, 90, 91, 106, 113, 123, 175, 177, 178, 179, 180, 181, 190, 207, 209, 228, 301 Osmosis, 301, 302 Osmotic, 52, 251, 302, 316 Osteoporosis, 20, 302 Ovaries, 302, 321 Ovary, 34, 302 Overexpress, 29, 302 Overweight, 16, 29, 130, 214, 302 Ovum, 270, 281, 291, 302, 309 Oxidants, 50, 204, 302 Oxidation, 6, 18, 23, 35, 50, 205, 249, 255, 256, 259, 269, 271, 292, 302 Oxidation-Reduction, 259, 302 Oxidative Stress, 31, 50, 106, 302 P Palladium, 199, 302 Palliative, 302, 321 Pancreas, 30, 85, 99, 140, 151, 156, 171, 217, 218, 249, 289, 290, 302, 303, 318, 324 Pancreatic Ducts, 42, 303 Pancreatic enzymes, 207, 303 Pancreatic Insufficiency, 41, 69, 72, 151, 160, 171, 197, 303

Pancreatic Juice, 116, 303 Pancreatin, 138, 303 Pancreatitis, 41, 79, 86, 90, 112, 119, 121, 151, 196, 218, 303 Paraffin, 11, 303 Parasite, 46, 303 Parasitic, 258, 303 Parietal, 217, 303, 304 Parietal Lobe, 303 Particle, 18, 37, 59, 87, 106, 138, 141, 174, 296, 303, 323 Parturition, 303, 309 Pathogen, 39, 47, 182, 303 Pathogenesis, 12, 16, 31, 39, 42, 44, 51, 55, 194, 303 Pathologic, 43, 269, 303, 325 Pathologic Processes, 43, 303 Pathologies, 33, 303 Pathophysiology, 5, 20, 25, 50, 52, 217, 303 Pedigree, 47, 73, 303 Pelvis, 249, 293, 302, 303, 325 Pentoxifylline, 127, 303 Pepsin, 304 Pepsinogens, 218, 304 Peptide Hydrolases, 275, 286, 304 Perciformes, 304, 315 Perennial, 277, 304, 324 Perfusion, 26, 304, 322 Perinatal, 31, 304 Periodicity, 6, 304 Peripheral Nervous System, 300, 304, 309, 318, 320 Peripheral Neuropathy, 32, 304 Peritoneal, 217, 289, 304 Peritoneal Cavity, 289, 304 Peritoneum, 304 Perivascular, 296, 304 Pernicious anemia, 290, 304 Peroneal Nerve, 304, 315 Peroxidase, 168, 256, 292, 305 Peroxide, 305 Pesticides, 43, 195, 289, 305 Petrolatum, 274, 305 Petroleum, 303, 305 Phagocyte, 302, 305 Phagocytosis, 296, 305 Pharmaceutic Aids, 279, 305 Pharmaceutical Preparations, 263, 277, 280, 305 Pharmacokinetic, 305 Pharmacologic, 9, 36, 60, 305, 322, 323 Pharmacotherapy, 8, 305

340

Lipase

Phenolphthalein, 274, 305 Phenotype, 5, 11, 15, 21, 78, 305 Phenyl, 215, 305 Phenylalanine, 305, 324 Phorbol, 53, 305 Phosphates, 38, 173, 305 Phosphatidic Acids, 294, 305 Phosphodiesterase, 46, 303, 305 Phospholipases, 6, 7, 25, 55, 139, 306 Phospholipases A, 25, 306 Phospholipids, 11, 22, 25, 34, 37, 46, 92, 94, 139, 169, 196, 205, 278, 289, 292, 295, 306 Phosphoric Monoester Hydrolases, 286, 306 Phosphorous, 187, 306 Phosphorus, 260, 306 Phosphorylase, 61, 306 Phosphorylase a, 306 Phosphorylase b, 306 Phosphorylase Kinase, 61, 306 Phosphorylated, 68, 265, 306 Phosphorylation, 20, 30, 36, 38, 43, 44, 56, 68, 105, 152, 154, 196, 306 Physical Fitness, 222, 306 Physicochemical, 137, 306 Physiologic, 23, 31, 53, 251, 259, 295, 306, 312, 320 Phytotoxin, 306, 314 Pigment, 55, 129, 155, 168, 203, 258, 264, 292, 306 Pitch, 199, 306 Pituitary Gland, 278, 307, 310 Placenta, 50, 307, 309 Plant Oils, 128, 301, 307 Plants, 168, 182, 191, 192, 196, 212, 213, 252, 256, 258, 261, 264, 277, 281, 283, 297, 300, 306, 307, 308, 311, 315, 323, 324, 325 Plaque, 5, 107, 257, 307 Plasma cells, 254, 307 Plasma protein, 251, 307, 316 Plasmin, 51, 307 Plasminogen, 12, 45, 307 Plasminogen Activators, 307 Plastids, 301, 307 Platelet Aggregation, 140, 253, 300, 303, 307, 321 Platelets, 74, 256, 300, 307, 321 Platinum, 293, 302, 307 Plexus, 307, 315 Pneumonia, 268, 308 Poisoning, 43, 295, 298, 308

Polyesters, 185, 308 Polyethylene, 145, 308 Polymerase, 12, 157, 308, 313 Polymerase Chain Reaction, 12, 157, 308 Polymorphic, 8, 72, 264, 271, 308 Polymorphism, 19, 28, 35, 45, 77, 79, 80, 83, 88, 99, 100, 103, 110, 112, 120, 123, 308 Polypeptide, 139, 198, 211, 212, 218, 252, 253, 266, 278, 280, 307, 308, 309, 310, 318, 327 Polysaccharide, 53, 255, 263, 308, 311 Polyunsaturated fat, 134, 139, 142, 143, 148, 152, 157, 169, 176, 308, 321 Posterior, 253, 263, 290, 296, 302, 308 Postmenopausal, 16, 20, 35, 117, 302, 308 Postnatal, 28, 308 Postprandial, 26, 49, 67, 83, 89, 90, 91, 92, 116, 138, 139, 140, 152, 182, 308 Post-translational, 52, 138, 308 Potassium, 204, 272, 308, 317 Potentiates, 289, 308 Potentiation, 135, 309 Practice Guidelines, 234, 309 Pravastatin, 45, 309 Precursor, 65, 186, 212, 254, 256, 264, 272, 274, 275, 276, 300, 305, 307, 309, 324, 326 Predisposition, 21, 36, 309 Preeclampsia, 31, 50, 164, 309 Prenatal, 274, 309 Presynaptic, 299, 300, 309 Presynaptic Terminals, 299, 309 Prevalence, 6, 22, 23, 32, 36, 44, 100, 221, 309 Prodrug, 215, 309 Progesterone, 309, 319 Progression, 10, 11, 15, 107, 108, 224, 254, 309 Progressive, 263, 265, 270, 273, 298, 309, 313 Prolactin, 102, 309 Proline, 69, 266, 286, 309 Promoter, 27, 29, 32, 36, 61, 64, 81, 85, 88, 95, 96, 100, 120, 122, 127, 128, 309 Pro-Opiomelanocortin, 27, 275, 309 Prophylaxis, 169, 215, 310 Propionibacterium, 72, 104, 127, 135, 141, 156, 310 Propionibacterium acnes, 72, 104, 127, 135, 141, 156, 310 Prospective study, 7, 24, 310 Prostaglandins, 201, 252, 256, 274, 288, 310

341

Prostaglandins A, 201, 288, 310 Prostaglandins D, 310 Protease, 41, 50, 64, 73, 77, 144, 147, 168, 169, 187, 192, 203, 303, 310 Protease Inhibitors, 50, 168, 310 Protein Binding, 34, 310, 322 Protein C, 180, 192, 200, 204, 251, 253, 255, 257, 265, 292, 310, 325 Protein Conformation, 253, 310 Protein S, 34, 52, 259, 276, 281, 310, 314, 321 Proteinuria, 299, 309, 310 Proteoglycan, 10, 311 Proteolytic, 51, 77, 136, 252, 266, 275, 278, 307, 311, 314 Protocol, 188, 311 Protons, 252, 285, 290, 311, 312 Protozoa, 47, 267, 296, 311, 325 Protozoal, 311 Protozoan, 46, 311 Psychiatric, 41, 311 Psychiatry, 8, 311 Psychoactive, 311, 321 Psychology, 272, 311 Public Policy, 233, 311 Publishing, 60, 311 Pulmonary, 259, 268, 311, 320, 325 Pulmonary Artery, 259, 311, 325 Pulse, 297, 311 Purifying, 185, 195, 201, 202, 271, 311 Purines, 258, 311, 316, 327 Pyrimidines, 258, 312, 316 Q Quality of Life, 50, 192, 312 R Race, 53, 117, 185, 188, 194, 195, 199, 201, 296, 312 Racemic, 53, 185, 188, 194, 195, 199, 201, 312 Radiation, 217, 254, 275, 279, 290, 312, 315, 327 Radioactive, 259, 285, 293, 297, 300, 312, 315 Radiolabeled, 42, 43, 312 Randomized, 21, 24, 45, 113, 274, 312 Reabsorption, 177, 179, 207, 312 Reaction Time, 188, 312 Reactivation, 137, 312 Reactive Oxygen Species, 6, 312 Reagent, 14, 277, 285, 312 Receptors, Serotonin, 312, 316

Recombinant, 52, 55, 58, 65, 74, 116, 129, 171, 189, 196, 198, 211, 212, 312, 325 Recombination, 211, 267, 281, 312 Reconstitution, 52, 312 Rectum, 255, 260, 266, 270, 272, 278, 280, 288, 291, 312, 320 Recur, 304, 313 Recurrence, 304, 313 Red blood cells, 276, 313, 315, 317 Reductase, 45, 138, 142, 293, 296, 309, 313, 317 Refer, 1, 14, 260, 266, 275, 279, 293, 294, 299, 300, 313, 323 Refraction, 313, 318 Regeneration, 278, 312, 313 Regimen, 274, 305, 313 Regurgitation, 284, 313 Renal Artery, 286, 313 Renal failure, 15, 92, 313, 324 Renin, 15, 254, 313 Renin-Angiotensin System, 15, 254, 313 Repressor, 301, 313 Reproductive cells, 281, 313 Respiration, 261, 297, 313 Resting metabolic rate, 35, 313 Restitution, 52, 313 Reticulata, 155, 314 Retina, 267, 294, 301, 314, 315 Retinal, 55, 129, 155, 301, 314 Retinoid, 54, 314 Retinol, 49, 54, 314 Retinyl palmitate, 54, 314 Retrovirus, 33, 314 Rheology, 303, 314 Rheumatism, 287, 314 Rheumatoid, 266, 302, 314 Rhodopsin, 301, 314 Ribonucleic acid, 16, 314 Ribosome, 314, 323 Ricin, 69, 145, 314 Rickets, 314, 326 Risk factor, 6, 8, 12, 13, 16, 20, 22, 40, 45, 47, 59, 194, 218, 222, 310, 315 Risk patient, 5, 315 Rod, 55, 257, 260, 310, 311, 315 Rosiglitazone, 51, 315 S Salicylic, 67, 315 Saline, 315 Saliva, 315 Salivary, 207, 315 Saponins, 148, 315, 319

342

Lipase

Satellite, 28, 315 Saturated fat, 140, 315 Scans, 36, 315 Sciatic Nerve, 33, 304, 315, 322 Screening, 8, 39, 97, 118, 155, 173, 265, 315 Sea Bream, 127, 129, 140, 203, 315 Secondary tumor, 296, 315 Secretory, 17, 30, 55, 70, 149, 219, 299, 316 Sedentary, 3, 8, 313, 316 Segregation, 312, 316 Semisynthetic, 265, 316 Senescence, 61, 191, 192, 316 Senile, 302, 316 Sepsis, 25, 38, 295, 316 Sequence Analysis, 67, 73, 75, 316 Sequence Homology, 52, 67, 316 Sequencing, 40, 45, 48, 65, 72, 154, 308, 316, 320 Sequester, 26, 178, 179, 207, 214, 316 Serine, 73, 103, 104, 126, 154, 173, 196, 275, 306, 316, 324 Serologic, 287, 316 Serotonin, 8, 271, 278, 279, 300, 305, 312, 316, 324 Serous, 266, 275, 316 Serum Albumin, 134, 316 Shock, 285, 316, 324 Sibutramine, 8, 316 Side effect, 49, 50, 172, 177, 178, 181, 214, 227, 250, 258, 286, 316, 317, 323 Silicon, 182, 183, 317 Silicon Compounds, 182, 183, 317 Silicon Dioxide, 317 Simvastatin, 91, 317 Skeletal, 46, 62, 68, 91, 99, 101, 103, 114, 140, 149, 164, 210, 221, 298, 317 Skeleton, 202, 249, 317 Skull, 301, 317, 321 Sludge, 147, 317 Small intestine, 46, 69, 180, 192, 197, 207, 262, 265, 273, 285, 287, 289, 317, 324, 326 Smooth muscle, 9, 71, 115, 150, 155, 252, 253, 260, 261, 268, 279, 285, 313, 317, 320 Soaps, 185, 278, 317 Social Environment, 312, 317 Sodium, 20, 172, 187, 202, 272, 283, 297, 312, 317 Sodium Fluoride, 20, 317 Soft tissue, 259, 310, 317 Solid tumor, 273, 317 Solvent, 53, 171, 176, 188, 194, 202, 210, 249, 277, 282, 302, 317

Soma, 318 Somatic, 28, 118, 171, 304, 318 Somatic cells, 118, 171, 318 Somatostatin, 218, 318 Soybean Oil, 148, 308, 318 Specialist, 239, 318 Specificity, 44, 53, 94, 127, 172, 176, 182, 190, 251, 256, 261, 275, 318, 322 Spectroscopic, 27, 318 Spectrum, 14, 296, 318 Sperm, 265, 313, 318, 321 Spermatogenesis, 224, 318 Spermatozoa, 318 Sphincter, 155, 318 Spinal cord, 32, 156, 257, 260, 263, 264, 295, 299, 304, 315, 318 Spleen, 293, 294, 318 Spotting, 178, 190, 318 Staging, 315, 318 Steady state, 26, 318 Steatorrhea, 42, 64, 151, 224, 319 Steatosis, 278, 319 Stellate, 49, 54, 319 Sterility, 75, 319 Steroid, 59, 144, 194, 258, 269, 315, 317, 319 Stimulant, 260, 285, 319 Stimulus, 193, 268, 273, 274, 277, 288, 290, 312, 319, 321 Stomachic, 172, 319 Stool, 190, 266, 288, 290, 291, 319 Strand, 65, 308, 319 Streptococcal, 292, 319 Stress, 50, 52, 59, 172, 193, 200, 262, 269, 290, 298, 302, 309, 319 Stroke, 24, 45, 84, 95, 107, 120, 205, 224, 232, 262, 263, 319 Stroma, 290, 319 Stromal, 51, 319 Structure-Activity Relationship, 14, 319 Subacute, 42, 288, 319 Subclinical, 288, 319 Subcutaneous, 16, 49, 78, 120, 250, 274, 292, 319, 326, 327 Subiculum, 284, 319 Subspecies, 45, 107, 318, 319 Substance P, 276, 296, 312, 316, 320 Substrate Specificity, 54, 89, 102, 195, 197, 320 Superoxide, 6, 50, 83, 320 Superoxide Dismutase, 83, 320 Supplementation, 140, 142, 145, 320 Suppositories, 280, 320

343

Suppression, 11, 50, 70, 320 Suppressive, 11, 320 Surfactant, 51, 171, 172, 176, 189, 190, 193, 195, 209, 277, 320 Swainsonine, 144, 320 Sympathomimetic, 273, 276, 300, 320 Symptomatic, 303, 320 Synapse, 250, 299, 309, 320, 323 Synaptic, 300, 320 Synchrony, 30, 320 Synergistic, 10, 309, 320 Systemic, 6, 25, 42, 44, 119, 175, 217, 228, 259, 266, 276, 288, 299, 320, 323, 325 Systolic, 286, 320 T Taurine, 177, 179, 207, 258, 320 Teichoic Acids, 283, 321 Temporal, 284, 294, 321 Tendon, 266, 321 Tenotomy, 149, 321 Teratogenesis, 43, 321 Teratoma, 119, 321 Testicles, 321 Testosterone, 119, 313, 321 Tetracycline, 52, 65, 75, 321 Tetrahydrocannabinol, 13, 41, 321 Therapeutics, 106, 138, 196, 228, 321 Thermal, 272, 300, 308, 321 Thorax, 249, 293, 321 Threonine, 316, 321 Threshold, 286, 321 Thrombin, 278, 307, 310, 321 Thrombocytes, 307, 321 Thrombolytic, 307, 321 Thrombomodulin, 310, 321 Thrombosis, 79, 89, 92, 95, 96, 109, 110, 111, 114, 138, 154, 310, 319, 321 Thromboxanes, 256, 274, 321 Thrombus, 269, 288, 298, 307, 321 Thymus, 287, 293, 294, 322 Thyroid, 53, 286, 322, 324 Thyroid Gland, 286, 322 Thyroid Hormones, 322, 324 Thyrotropin, 18, 287, 322 Thyroxine, 251, 305, 322 Tibial Nerve, 315, 322 Tissue, 10, 11, 14, 15, 16, 17, 18, 23, 32, 33, 35, 37, 41, 44, 46, 47, 48, 49, 53, 62, 66, 68, 69, 74, 75, 76, 77, 81, 83, 102, 120, 127, 129, 140, 142, 149, 155, 157, 169, 190, 195, 197, 207, 210, 221, 249, 250, 251, 255, 256, 257, 258, 259, 261, 264,

266, 268, 273, 274, 277, 278, 279, 280, 282, 287, 289, 291, 292, 293, 294, 295, 298, 299, 301, 303, 304, 306, 307, 313, 314, 316, 317, 318, 319, 320, 321, 322, 323, 324, 327 Tissue Culture, 299, 322 Tissue Distribution, 197, 322 Tolerance, 16, 204, 282, 322 Tomography, 322 Tone, 300, 322 Tonic, 319, 322 Tooth Preparation, 249, 322 Topical, 186, 257, 277, 286, 303, 305, 317, 322 Toxaemia, 309, 322 Toxic, iv, 218, 251, 258, 268, 270, 273, 275, 299, 306, 323 Toxicity, 28, 42, 43, 51, 53, 273, 295, 323 Toxicokinetics, 323 Toxicology, 43, 133, 157, 234, 323 Toxin, 149, 275, 322, 323 Trace element, 265, 317, 323 Trachea, 260, 322, 323 Transcriptase, 314, 323 Transcription Factors, 23, 51, 323 Transduction, 6, 7, 9, 20, 30, 43, 52, 55, 56, 289, 323 Transfection, 51, 259, 281, 323 Transfer Factor, 287, 323 Transferases, 283, 323 Translation, 19, 23, 29, 53, 74, 252, 276, 323 Translational, 53, 323 Translocation, 6, 30, 34, 71, 276, 323 Transmitter, 249, 257, 272, 290, 295, 300, 323 Transplantation, 287, 294, 323 Transversion, 112, 323 Trauma, 118, 193, 217, 284, 298, 303, 324 Trees, 277, 324 Triad, 31, 196, 324 Tributyrin, 158, 324 Troglitazone, 50, 324 Trypsin, 33, 219, 275, 324, 327 Tryptophan, 58, 266, 316, 324 Tuberculosis, 39, 293, 315, 324 Tumor Necrosis Factor, 66, 74, 89, 324 Tunica, 297, 324 Tunicamycin, 144, 324 Type 2 diabetes, 44, 49, 56, 81, 96, 108, 115, 120, 121, 141, 263, 324 Tyrosine, 135, 154, 272, 324

344

Lipase

U Ubiquitin, 299, 324 Ulcer, 270, 273, 324 Ulceration, 270, 324 Unsaturated Fats, 278, 324 Uraemia, 303, 324 Urea, 169, 324, 325 Uremia, 313, 325 Urethra, 325 Uric, 252, 283, 286, 312, 325 Urinary, 261, 288, 325, 327 Urine, 86, 259, 269, 272, 288, 291, 310, 325 Uterus, 270, 279, 295, 302, 309, 325 V Vaccines, 325, 326 Vacuoles, 275, 301, 325 Vagina, 295, 318, 325 Vascular Resistance, 253, 325 Vasculitis, 303, 325 Vasoactive, 218, 325 Vasoconstriction, 276, 325 Vasodilator, 255, 260, 273, 285, 325 Vector, 189, 323, 325 Vegetative, 258, 325 Vein, 177, 205, 207, 290, 300, 315, 325 Venous, 12, 260, 310, 325 Venous blood, 12, 260, 325 Ventricle, 268, 284, 286, 311, 320, 325, 326 Ventricular, 15, 24, 253, 268, 320, 326 Vertebrae, 318, 326 Very low-density lipoprotein, 105, 326 Vesicular, 296, 326 Veterinary Medicine, 233, 326 Villi, 192, 326 Villous, 262, 326 Villus, 52, 326 Viral, 32, 314, 323, 326

Virulence, 39, 257, 323, 326 Virus, 122, 257, 275, 281, 307, 323, 326 Viscera, 318, 326 Visceral, 13, 16, 35, 49, 89, 123, 127, 129, 140, 150, 304, 326 Visceral fat, 13, 35, 50, 326 Viscosity, 168, 190, 314, 326 Vitamin A, 54, 288, 314, 326 Vitamin D, 17, 314, 326 Vitellogenin, 139, 326 Vitro, 18, 20, 29, 31, 32, 36, 37, 39, 43, 47, 50, 51, 52, 54, 56, 63, 65, 68, 70, 83, 94, 101, 103, 105, 118, 122, 128, 134, 138, 139, 140, 148, 157, 158, 175, 209, 281, 284, 287, 308, 322, 326 Vivo, 5, 7, 17, 18, 25, 29, 31, 33, 37, 41, 42, 43, 44, 46, 51, 52, 53, 56, 62, 63, 68, 83, 91, 104, 118, 175, 193, 209, 281, 284, 287, 302, 321, 326 Volition, 290, 326 Voltage-gated, 30, 326 W Waist circumference, 3, 16, 263, 326 White blood cell, 15, 254, 266, 288, 291, 293, 294, 297, 307, 327 Windpipe, 322, 327 Wound Healing, 278, 327 X Xanthine, 50, 252, 327 Xanthine Oxidase, 50, 252, 327 Xanthophyll, 201, 202, 327 Xenograft, 254, 327 X-ray, 66, 267, 268, 279, 300, 315, 327 Y Yeasts, 185, 202, 279, 305, 327 Z Zymogen, 310, 327

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