GLUCAGON 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., 1960Glucagon: 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: 0-497-00484-4 1. Glucagon-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on glucagon. 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 GLUCAGON ............................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Glucagon ....................................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 67 The National Library of Medicine: PubMed ................................................................................ 78 CHAPTER 2. NUTRITION AND GLUCAGON ................................................................................... 125 Overview.................................................................................................................................... 125 Finding Nutrition Studies on Glucagon.................................................................................... 125 Federal Resources on Nutrition ................................................................................................. 128 Additional Web Resources ......................................................................................................... 129 CHAPTER 3. ALTERNATIVE MEDICINE AND GLUCAGON ............................................................. 131 Overview.................................................................................................................................... 131 National Center for Complementary and Alternative Medicine................................................ 131 Additional Web Resources ......................................................................................................... 145 General References ..................................................................................................................... 146 CHAPTER 4. DISSERTATIONS ON GLUCAGON ............................................................................... 147 Overview.................................................................................................................................... 147 Dissertations on Glucagon......................................................................................................... 147 Keeping Current ........................................................................................................................ 148 CHAPTER 5. PATENTS ON GLUCAGON ......................................................................................... 149 Overview.................................................................................................................................... 149 Patents on Glucagon.................................................................................................................. 149 Patent Applications on Glucagon .............................................................................................. 163 Keeping Current ........................................................................................................................ 177 CHAPTER 6. BOOKS ON GLUCAGON ............................................................................................. 179 Overview.................................................................................................................................... 179 Book Summaries: Federal Agencies............................................................................................ 179 Book Summaries: Online Booksellers......................................................................................... 182 The National Library of Medicine Book Index ........................................................................... 182 Chapters on Glucagon................................................................................................................ 182 CHAPTER 7. PERIODICALS AND NEWS ON GLUCAGON ............................................................... 185 Overview.................................................................................................................................... 185 News Services and Press Releases.............................................................................................. 185 Newsletter Articles .................................................................................................................... 186 Academic Periodicals covering Glucagon .................................................................................. 187 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 189 Overview.................................................................................................................................... 189 U.S. Pharmacopeia..................................................................................................................... 189 Commercial Databases ............................................................................................................... 190 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 193 Overview.................................................................................................................................... 193 NIH Guidelines.......................................................................................................................... 193 NIH Databases........................................................................................................................... 195 Other Commercial Databases..................................................................................................... 197 APPENDIX B. PATIENT RESOURCES ............................................................................................... 199 Overview.................................................................................................................................... 199 Patient Guideline Sources.......................................................................................................... 199 Finding Associations.................................................................................................................. 202
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APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 205 Overview.................................................................................................................................... 205 Preparation................................................................................................................................. 205 Finding a Local Medical Library................................................................................................ 205 Medical Libraries in the U.S. and Canada ................................................................................. 205 ONLINE GLOSSARIES................................................................................................................ 211 Online Dictionary Directories ................................................................................................... 213 GLUCAGON DICTIONARY....................................................................................................... 215 INDEX .............................................................................................................................................. 289
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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 glucagon is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about glucagon, 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 glucagon, 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 glucagon. 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 glucagon, 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 glucagon. 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 GLUCAGON Overview In this chapter, we will show you how to locate peer-reviewed references and studies on glucagon.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and glucagon, 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 “glucagon” (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: •
Mini-Dose Glucagon Rescue for Hypoglycemia in Children with Type 1 Diabetes Source: Diabetes Care. 24(4): 643-645. April 2001. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article describes a study that tested the hypothesis that the use of small, subcutaneous doses of aqueous glucagon and home glucose monitoring would prevent or treat mild hypoglycemia in diabetic children and adolescents with oppositional behavior or with gastroenteritis without increasing the frequency of vomiting. The study analyzed 33 episodes of impending or mild hypoglycemia in 28 children. All were healthy except for type 1 diabetes and an episode of gastroenteritis. Using a standard U100 insulin syringe, children ages 2 years or less received two units of glucagon
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subcutaneously and those 2 to 15 received one unit per year of age up to 15 units. Patients older than 15 received only 15 units. If blood glucose did not increase within 30 minutes, the initial dosage was doubled and given at that time. Standard self monitoring techniques for blood glucose were used. The study found that blood glucose was 3.44 plus or minus 0.15 mmol per liter before and 8.11 plus or minus 0.72 mmol per liter 30 minutes after glucagon. In 14 children, relative hypoglycemia recurred, requiring treatment. In four children, a third dose was required. The glucagon was well tolerated. In 28 of the 33 episodes of impending hypoglycemia, the children remained at home and fully recovered. Five children were taken to their local hospital because of concerns of dehydration or fever, but none for hypoglycemia. The article concludes that minidose glucagon rescue, using subcutaneous injections, is effective in managing children with type 1 diabetes during episodes of impending hypoglycemia due to gastroenteritis or poor oral intake of carbohydrate. 1 figure. 6 references. (AA-M). •
Hurry! Get the Glucagon! Source: Diabetes Forecast. 51(1): 44-48. January 1998. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article provides information about using glucagon. Glucagon is a hormone that is produced in the pancreas and raises blood glucose. Like insulin, glucagon must be injected. The authors note that anyone who uses insulin or a sulfonylurea is at risk for severe hypoglycemia and therefore may require glucagon. Glucagon is not of value to the person with diabetes unless someone close by can recognize severe hypoglycemia, has glucagon available, and knows how to give it. Glucagon should be injected when a person with diabetes is unable to take sugar by mouth to treat low blood glucose. Two formulations of glucagon, which are available by prescription and equally effective, are the Glucagon Emergency Kit, and a two-vial combination, one containing crystals and the other containing diluting fluid. The article notes that glucagon is good for two years from the date of manufacture. The authors conclude that people with diabetes should talk to their health care team, make sure everyone in the family knows where to find the glucagon kit, and review the instructions enclosed with the glucagon kit on a regular basis. Instructions and accompanying illustrations help readers learn to prepare and inject glucagon. A sidebar quizzes family members about glucagon. (AA-M).
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Impact of Pramlintide on Glucose Fluctuations and Postprandial Glucose, Glucagon, and Triglyceride Excursions Among Patients with Type 1 Diabetes Intensively Treated with Insulin Pumps Source: Diabetes Care. 26(1): 1-8. January 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 assess the effects of adjunctive treatment with pramlintide, an analog of the beta cell hormone amylin, on 24 hour glucose fluctuations and postprandial (after a meal) glucose, glucagon, and triglyceride excursions in patients with type 1 diabetes who are intensively treated with continuous subcutaneous insulin infusion (CSII). In the study, 18 patients (16 of whom could be evaluated) with type 1 diabetes (aged 44 years, plus or minus 11 years) were given mealtime injections of pramlintide three times a day for 4 weeks in addition to their preexisting CSII regimen (16 lispro, 2 regular insulin). At baseline, patients had
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excessive 24 hour glucose fluctuations, with 59 percent of the continuous glucose monitoring system (CGMS) measurements greater than 140 milligrams per deciliter, 13 percent less than 90 milligrams per deciliter, and only 28 percent in the euglycemic (good levels of blood glucose) range. After 4 weeks on pramlintide, measures in the hyperglycemic range declined to 48 percent and measurements within the euglycemic range increased to 37 percent. This shift from the hyperglycemic to the euglycemic range occurred with a concomitant 17 percent reduction in mealtime insulin dosages and without relevant increases in measurements below the euglycemic range (15 percent) or any severe hypoglycemic events. 3 figures. 1 table. 26 references.
Federally Funded Research on Glucagon The U.S. Government supports a variety of research studies relating to glucagon. 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 glucagon. 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 glucagon. The following is typical of the type of information found when searching the CRISP database for glucagon: •
Project Title: ADMINISTRATION OF GLP 1 BY SUBCUTANEOUS DELIVERY-DETERMINATION OF DOSE Principal Investigator & Institution: Nathan, David M.; Principal Investigator; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADRENERGIC MECHANISMS IN PATHOPHYSIOLOGY--GLUCAGON IN GLUCOSE CONTERREG
METABOLIC
Principal Investigator & Institution: Cryer, Philip E.; Professor of Endocrinology and Metabolis; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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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Project Title: ALPHA AND BETA CELL FUNCTION IN NORMAL AND DIABETIC MAN Principal Investigator & Institution: Gerich, John E.; Professor of Medicine; Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-DEC-1986; Project End 31-DEC-2002 Summary: (Adapted from Applicant's Abstract): Hypoglycemia is a common and potentially serious problem for diabetic patients regardless of whether they are treated with insulin or oral agents. Conventional risk factors (wrong insulin doses, skipped or delayed meals, exercise) explain only a small percentage of episodes. However, hypoglycemia unawareness and abnormal glucose counterregulation have recently been identified as likely explanations for many cases. The overall goal of this grant is to delineate the mechanisms responsible for hypoglycemia unawareness and for abnormal glucose counterregulation in diabetic patients. The Specific Aims of the grant application are: A) To establish the mechanisms responsible for hypoglycemia unawareness in insulin dependent Type I diabetes. The investigators will; 1) establish the normal threshold for induction of hypoglycemia unawareness by hypoglycemia and test the hypothesis that in diabetic patients the threshold is reduced; 2) test the hypothesis that hypoglycemia unawareness in diabetic individuals involves diminished beta adrenergic sensitivity; 3) test the hypothesis that hypoglycemia per se reduces beta adrenergic sensitivity; 4) test the hypothesis that there are two types of hypoglycemia unawareness - an acute reversible type due to recurrent hypoglycemia and another chronic irreversible type related to duration of diabetes, possibly representing an encephalopathic complication of diabetes. B) To assess the mechanisms responsible for impaired glucose counterregulation in noninsulin dependent diabetes mellitus. The investigator will test the hypotheses that 1) reduced glucagon responses are due to increased plasma free fatty acid levels; 2) that increased catecholamine responses are secondary (e.g. compensatory) to reduced glucagon responses; 3) that increased catecholamine responses are in part the result of poor metabolic control; 4) that subnormal increase in glucose production during hypoglycemia results from impaired glucagon responses; 5) that enhanced suppression of glucose utilization results from the effects of increased catecholamine responses on muscle; and 6) that increased muscle glycogenolysis provides gluconeogenic precursors and promotes the compensatory increase in glucose production observed during hypoglycemia. To achieve these aims the investigator will use a combination of glucose clamp, isotope and limb balance techniques in conjunction with pharmacologic interventions in normal volunteers and in research subjects having either Type I or Type II diabetes. Better understanding of the pathogenesis of hypoglycemia unawareness and abnormal glucose counterregulation should make treatment of diabetes safer and improve the chances of achieving optimal glycemic control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AUTONOMIC NERVOUS SYSTEM REGULATION OF GLUCAGON SECRETION IN RHESUS MONKEYS Principal Investigator & Institution: Havel, Peter J.; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BETA-CELL METABOLISM AND INSULIN SECRETION Principal Investigator & Institution: Rocheleau, Jonathan V.; Diabetes Research and Trng Ctr; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-SEP-2002 Summary: Islets of Langerhans are pancreatic micro-organs that play a central role in blood glucose homeostasis by secreting insulin, glucagon, and other hormones in a regulated manner. The overall goal of this research is to quantitatively determine the biochemical dynamics involved in glucose- stimulated insulin secretion from intact pancreatic islets. More specifically, this study will address the role that cytoplasmic pH has on pyruvate transport into mitochondria, and will also address the role that cytoplasmic pH has on pyruvate transport into mitochondria, and will also address the role of mitochondria NADPH-shuttles in the insulin secretion process. In these studies, two-photon microscopy will be used to non-invasively monitor cellular NAD(P)H levels, with the ability to spatially separate signals from the cytoplasm and mitochondria. Metabolism will be correlated with beta-cell function by monitoring insulin secretion using established techniques such as radioimmuno assays and amperometry, or using fluorescence methods if feasible. Established fluorescence methodologies will be used to assay the cytoplasmic pH during nutrient stimulation. All studies will be mirrored in the NS-1 cell line, a classic cell culture model for beta-cells, which will allow a specific validations of this heavily used cell culture model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOACTIVE POLYMERS FOR EFFECTIVE ISLET DELIVERY SYSTEM Principal Investigator & Institution: Bae, You Han.; Professor; Pharmaceutics and Pharmaceutl Chem; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 31-JAN-2004 Summary: The goals of this application are to improve the functionality (insulin secretion rate and pattern) and to expand the life-span of immunoprotected pancreatic islets. The low functionality (less than 15% of the insulin release rate of native islets in pancreas) required a large number of islets within the implant, which causes complications in surgery and discomfort for patients. The limited life-span of the islets in a biohybrid artificial pancreas (BAP) may require frequent cell reseeding and cause further supply problems in islet transplantation. Improved islet functionality and prolonged life-span will minimize the volume of the BAP by reducing the number of islets needed for diabetic patients to achieve normoglycaemia and reduce probes associated with islet supply. It is hypothesized in this research that 1) my mimicking facilitated oxygen transport in avascular tissues, the immunoprotected islets release a higher amount of insulin, recover their intrinsic biphasic release pattern, and prolong their life-span, and 2) insulinotropic agents further promote insulin secretion from islets. Based on these hypotheses, a new BAP system will be designed which contains the water-soluble polymeric conjugates of oxygen carriers (or oxygen binding vesicles) and islet stimulants of sulfonylurea compounds and glucagon-like insulinotropic peptide-1 with entrapped islets in the BAP. The research examines their effects on islet viability, the amount of insulin secretion, the insulin release profile, and the life-span of immunoprotected pancreatic islets. Especially, the combined synergy effects of both hypotheses will be emphasized. The successful results in improving functionality and life-span of islets entrapped in an immunoprotected membrane can be applied in the delivery of micro-encapsulated therapeutic cells and to the miniaturization of a BAP. In
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addition, the approaches proposed in this research will provide a potential solution to the shortage problem of human cell or tissue sources. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAINSTEM MECHANISMS OF STRESS REGULATION Principal Investigator & Institution: Herman, James P.; Professor; Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): Inappropriate processing of psychological stress is a major causal or complicating factor in affective disorders. Stress dysfunction takes the form of behavioral hyperreactivity and glucocorticoid hypersecretion, mediated by amygdalar and hypothalamic effector circuits, respectively. Previous work has suggested that psychogenic stressors are predominantly processed in the forebrain, relayed to the effector neurons by descending corticolimbic inputs. Our group has recent findings that challenge this view, and thereby offer a potential new approach to treatment of stress-related disorders. Our results indicate that glucagon-like peptide-1 (GLP-I), a neuropeptide synthesized only in the brainstem, plays a major role in promoting both neuroendocrine and behavioral responses to psychogenic stressors. This has led us to hypothesize that the brainstem GLP-1 system may comprise a general coordinator of stress responses. To test this hypothesis, we propose four Specific Aims. In Aim 1, we will perform anatomical studies to evaluate the hypothesis that the GLP- 1 system selectively targets corticotropin-releasing hormone effector neurons in hypothalamic and amygdalar circuits, and determine whether GLP-1 neurons have collateral projections to both regions. Aim 2 will test the hypothesis that GLP-1 neurons are activated by psychogenic, interoceptive and conditioned stressors, and thus occupy a central role in generalized stress integration. Specific experiments will assess Fos expression in GLP-1 neurons as a measure of neuronal activation, address potential signaling pathways affecting GLP-1 neuronal activation, and demonstrate stress effects on transcription of the preproglucagon gene expression. Aim 3 will test the hypothesis that GLP-1 systems are persistently activated by chronic stress or glucocorticoids, providing a mechanism whereby prolonged stimulation can promote inappropriate behavioral and neuroendocrine responses. Finally, Aim 4 will test whether GLP-1 systems are necessary and sufficient for chronic stress-induced pathologies, testing the ability of exogenous GLP- 1 or a GLP- 1 receptor antagonist to cause or block, respectively, behavioral and endocrine changes characteristic of chronic stress. The results of these studies are expected to establish a major role for GLP-1 systems in stress regulation, and identify the GLP-1 system as a target for future therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CA SENSING FOR EXOCYTOSIS Principal Investigator & Institution: Gillis, Kevin D.; Assistant Professor; Dalton Research Center; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2004 Summary: (Applicant's Abstract) The secretion of neurotransmitter and hormones from neurons and neuroendocrine cells is a highly regulated process. It is now widely accepted that a rise in intracellular [Ca2+] rapidly triggers secretion from excitable cells. However, it has recently become clear that Ca2+ also slowly modulates ("primes") release, in part through activation of protein kinase C (PKC), which, in turn, accelerates
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the rate that secretory vesicles become ready to be released. Therefore it is likely that there are multiple fast (triggering) and slow (modulating) Ca2+ sensors for exocytosis. A long-range goal of the investigator is to understand how Ca2+ triggers exocytosis from excitable cells and how exocytosis is regulated by Ca2+ and other second messengers. The goal of this project is to characterize fast and slow Ca2+ sensing for exocytosis in individual cells using optical and electrophysiological techniques which allow both fine control of [Ca2+] and high-time-resolution measurements of exocytosis. The 3 aims are: Aim I. To determine how the protein SNAP-25 is involved in Ca2+ priming and triggering steps. The effect of mutations of SNAP-25 on exocytosis will be measured to test the hypothesis that the C-terminus of the protein participates in both Ca2+-priming and triggering steps. Aim II. To determine how fast Ca2+ can prime exocytosis. Experiments will elevate [Ca2+]i in 2 steps to sequentially prime and trigger secretion to test the hypothesis that Ca2+ priming occurs in less than 1 second. Aim III. To quantify the ionic selectivity of the Ca2+ trigger for exocytosis. Multivalent cations such as Sr2+, Ba2+, and Pb2+ can act as "Ca2+ surrogates" in triggering exocytosis and other Ca2+activated cellular responses. The ability of Ca2+ surrogates to rapidly trigger exocytosis will be measured to provide clues about the approximate size, flexibility and accessibility of the Ca2+-binding cavity of the triggering Ca2+ sensor. Achieving these aims will provide new insights into the mechanisms whereby secretion is regulated. Such basic knowledge is essential to understand complex processes such as short-term memory formation in the brain, the modulation of insulin secretion by glucagon in the endocrine pancreas, and the neurotoxicity of Pb2+ in the central nervous system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CA/NA EXCHANGERS--HORMONE & ETHANOL ACTION IN HEPATOCYTE Principal Investigator & Institution: Bernstein, Jaime; University of Puerto Rico Med Sciences Medical Sciences Campus San Juan, Pr 00936 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CAMP SIGNALING IN THE PANCREATIC B CELL Principal Investigator & Institution: Stoffers, Doris A.; Assistant Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Type 1 diabetes is an autoimmune disorder characterized by the selective destruction of pancreatic beta-cells. Therapeutic strategies to prevent beta -cell loss and/or replenish beta -cell mass would be highly beneficial for the treatment of this disease. Glucagon-like peptide-1 (GLP-1) is an intestinal hormone currently under investigation for use as a therapy for the treatment of type 2 diabetes. GLP-1 is an important regulator of the pancreatic beta-cell where it enhances glucoseinduced insulin secretion, increases proinsulin biosynthesis and stimulates insulin gene expression. In addition to regulating a -cell function, GLP-1 is a mitogen for pancreatic E-cells. The mechanism of action of GLP-1 is likely to be exceedingly complex. In pancreatic a - cells, the GLP-1 receptor couples to Gs to stimulate adenylyl cyclase and increase cAMP production. Similar to GLP-1, cAMP potentiates glucose-stimulated insulin secretion and stimulates a -cell proliferation. Although many of the effects of cAMP are mediated through PKA, it is now evident that PKA-dependent and -
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independent signals mediate the effects of cAMP in beta -cells and other endocrine cells. In thyroid follicular cells where thyrotropin regulates thyroid hormone biosynthesis and secretion as well as cell renewal, PKA-dependent and -independent signals contribute to cAMP-regulated function and proliferation. The goal of the proposed studies is to assess the role of cAMP-mediated signaling in GLP-1 action. Further, the contribution of PKAdependent and -independent signals to the regulation of beta -cell survival, proliferation and function are to be investigated. These studies will include an assessment of the roles of the small G protein RaplA, a direct target of cAMP, in a -cell growth and function, and of the transcription factor CREB, an important PKA target, in a-cell survival. The analysis of GLP-1 action will includes its effects on Akt and p70 ribosomal S6 kinase, protein kinases regulated selectively by cAMP in cells where it stimulates growth. The contribution of glucose and insulin/IGF-1 to GLP-1 effects in a-cells will be explored. Studies are to be carried out using rat insulinoma (INS-l) cells and all key findings confirmed in primary rat islets. The elucidation of the signaling modules through which GLP-1 regulates a-cell function, proliferation and survival will provide the fundamental knowledge required to facilitate the development of novel therapies for the treatment of diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANCER-RELATED REGULATION/TARGETING
GLYCOLYTIC
GENE--
Principal Investigator & Institution: Pedersen, Peter L.; Professor; Biological Chemistry; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 11-DEC-1998; Project End 30-NOV-2003 Summary: The long-term objective of this proposal is to characterize and target those molecular events responsible for one of the most common, profound, and intriguing phenotypes of malignant tissues, i.e., their elevated capacity to utilize glucose, a critical carbon and energy source essential for cell growth. In earlier studies we identified hexokinase, the initial enzyme of glucose catabolism, as a major player and showed that, of its four major isozymes,only Type II is both highly overexpressed in tumors and bound to the mitochondria. Here, the enzyme is unregulated and produces the key metabolic precursor Glu-6-P at high rates. More recently while working at the gene level, we have made some very novel, definitive, and exciting progress, which for the first time in more than 6 decades, begins to shed light on the underlying cause of the highly glycolytic phenotype characteristic of numerous human cancers. Thus, we have shown that the Type II hexokinase gene is amplified, and upon isolating and characterizing its promoter in detail, demonstrated that it is activated, not only by glucose, insulin, glucagon, and cAMP, but also by both hypoxic conditions (common within highly malignant tumors), and by a mutant form of the tumor suppressor p53. These preliminary studies form a firm foundation for the studies proposed here which are focused on better understanding how the cancer- related Type II hexokinase gene is regulated, and how it can be successfully inhibited. Specific aims are 4-fold and will be to: 1) Establish how the Type Il hexokinase gene, silent in many normal cells, e.g., hepatocytes, is "switched on" during tumorigenesis; 2) Elucidate the molecular basis underlying the activation of the Type II hexokinase gene promoter by glucose; 3) Gain greater insight into the molecular basis and significance of the novel finding, that within tumor cells, the promoter for Type II hexokinase is activated by a mutant form of p53; and 4) Identify methods for arresting the growth of highly malignant cancers by selectively inhibiting the expression of the Type II hexokinase gene using antisense RNA and targeted gene disruption techniques. These studies are fundamental to our
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11
understanding at the gene level of one of the most common phenotypes of cancer cells, and are likely to lead to novel approaches for controlling the growth of highly malignant tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CANDIDATE GENE FOR DIABETIC NEPHROPATHY--MEPRIN BETA Principal Investigator & Institution: Bond, Judith S.; Professor and Chair; Biochem and Molecular Biology; Pennsylvania State Univ Hershey Med Ctr 500 University Drive Hershey, Pa 170332390 Timing: Fiscal Year 2002; Project Start 14-AUG-1998; Project End 31-JUL-2003 Summary: The long-term goals of this research are to understand the role of proteases in the development of renal diseases, and particularly in the pathophysiology of DN. Recent segregation and linkage analyses of Pima Indians have identified a region on chromosome 18 indicated to have a major effect on the prevalence of DN. The only candidate gene identified in this region was the structural gene for meprin-b, a subunit of a membrane metalloprotease localized to the brush border membranes of renal proximal tubules. Meprin-b is capable of cleaving a variety of bioactive peptides and proteins, including glucagon, insulin B chain, parathyroid hormone, gastrin, cholecystokinin, protein kinase A, gelatin, and collagen. The focus of this application is to test the hypothesis that variation in the meprin-b gene (structural or regulatory regions) in Pima Indians results in the variable expression, targeting, activity, or stability of the meprin-b protein, and that this is related to the susceptibility to DN. In addition to analyzing DNA from Pima Indians with advanced DN or with long-standing diabetes without nephropathy, genetically modified mice that overexpress or are null for the meprin-b gene will be developed and examined for kidney function and susceptibility to DN. The Specific Aims of the application are to: 1) analyze the meprin-b gene from Pima Indians that developed DN and unaffected individuals; 2) determine whether mutations identified in patients with nephropathy affect biosynthesis, localization, stability, or activity or meprin-b in transfection experiments, and determine whether there are abnormalities in immunochemical localization of meprin-b in kidney cortex samples from-individuals with DN; 3) overexpress the meprin-b gene in transgenic mice, and determine the effects on kidney function and susceptibility to DN induced by streptozocin or in a genetic model of type 2 diabetes; and 4) investigate the meprin-b knock-out mouse for kidney function and susceptibility to DN. These studies will establish whether the meprin-b gene is associated with susceptibility to DN in humans, and provide animal models to determine the role of this proteinase in normal kidney and in susceptibility to renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CARBOHYDRATE METABOLISM IN LATE PREGNANCY Principal Investigator & Institution: Connolly, Cynthia C.; Molecular Physiol & Biophysics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2006 Summary: During late pregnancy, women with insulin-dependent diabetes (IDDM) are vulnerable to more frequent and more severe hypoglycemic episodes. The cause of this is not known, but has been suggested to be due in part to the intensive insulin treatment necessary to minimize perinatal morbidity and mortality. However, a few studies in pregnant women and the pregnant rat have indicated that the glucagon response, and
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probably the epinephrine response, to insulin-induced hypoglycemia is blunted by pregnancy itself. I have demonstrated in the pregnant dog that the increment in circulating norepinephrine is blunted as well, suggesting that a reduction in activation of the sympathetic nervous system in response to hypoglycemia may also accompany pregnancy. In the nonpregnant state, the magnitude of the counterregulatory hormone response appears to be modulated by a variety of factors that include sensitivity of the brain to insulin or the degree of hypoglycemia. The aim of this proposal is to examine which counterregulatory mechanisms are altered by pregnancy. The ensuing metabolic consequences of potential impairments will also be assessed. The techniques required to answer the questions posed are invasive and the experimental conditions are potentially harmful to the fetus. Thus, a novel canine model of pregnancy will be employed to address these issues. Arteriovenous difference techniques across the pancreas will be used to assess whether there is a defect in the alpha cell's ability to respond to a fall in glucose in pregnancy, and whether the defective glucagon response to insulin-induced hypoglycemia correlates with a decrease in neural drive to the pancreas. A technique for cannulation of the third cerebroventricle will be used to establish brain neuroglycopenia to assess whether pregnancy causes changes in the brain's sensitivity to hypoglycemia per se. Finally, the altered endocrine environment of pregnancy is the likely cause of the altered counterregulatory response, and three of the major hormones of pregnancy (estrogen, progesterone and prolactin) will be chronically elevated in nonpregnant female dogs to determine whether re-creating part of the hormonal environment of pregnancy attenuates the rise in counterregulatory hormones in response to insulininduced hypoglycemia, similar to that seen in pregnancy. The studies in this proposal should help to identify which counterregulatory mechanisms are affected by pregnancy, thereby potentially contributing to the more frequent and severe episodes of hypoglycemia experienced by pregnant women with diabetes. Preliminary studies in the pregnant dog model in fact suggest that multiple counterregulatory mechanisms are altered by pregnancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELL CELL ADHESION MOLECULES IN PANCREATIC ISLETS ONTOGENY & FUNCTION Principal Investigator & Institution: Cirulli, Vincenzino; Assistant Professor; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: Background: Histogenesis and organogenesis is believed to be directed by programmed cell-cell and cell-to-matrix interactions. Cell-cell adhesiveness is determined by specific cell adhesion molecules (CAMs), whose modular expression is also thought to regulate cell proliferation and/or differentiation. An important feature of CAMs is their developmentally regulated expression which appears to play important roles during histogenesis and organogenesis of various tissues including the pancreas. Their cell type-specific expression may therefore be used to identify cell populations at defined stages of development. Furthermore, CAMs are required for the maintenance of tissue architecture, which in turn is critical to organs' function. In fact, we have previously demonstrated that adhesion molecules such as NCAM are involved in the maintenance of the three-dimensional organization of pancreatic islet cells, with insulin-secreting ?-cells located in the core, and the other endocrine cell t ypes (??????and pp, secreting glucagon, somatostatin and pancreatic polypeptide, respectively??arranged at the periphery. This peculiar islet cell type segregation is perturbed in diabetes suggesting that such a configuration might be necessary for
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proper islet function. Objectives: Our current efforts focus on the identification and functional characterization of CAMs involved in the ontogeny of human pancreatic islets. Summary of the past year achievements: Experiments were designed to identify cell-cell adhesion molecules (CAMs) expressed by fetal pancreatic cells, and to understand their functional role in cell-cell adhesion, proliferation, and endocrine differentiation. In particular, we have identified EpCAM as a major mediator of pancreatic epithelial cell-cell adhesion. Interestingly, this CAM appeared to be involved in epithelial cell growth. Part of this work entailed use of the confocal microscope and the IVEM at the NCMIR. These data are the subject of a manuscript in preparation (1). In addition, based on our previous experience suggesting an important role of mesenchyme-derived growth factors such as HGF/SF in proliferation of human fetal pancreatic cells, we have examined the expression pattern of the C-MET receptor for HGF/SF within the human pancreas both in fetal and adult life. These eperiments have determined that C-MET is restricted to the epithelial compartment of the developping human pancreas, and that it becomes predominantly expressed on endocrine cells (islets of Langerhans) in the adult pancreas (2). Finally, our search for markers of endocrine differentiation led to the identification of GAD65 (Glutamic Acid Decarboxylase, 65kD) within epithelial cells entering the pathway of endocrine differentiatrion (i.e. insulin and/or glucagon expression). This study has also been recently accepted for publication (3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESPONSES
CENTRAL
GLP-1
SYSTEMS
IN
COUNTER
REGULATORY
Principal Investigator & Institution: Elmquist, Joel K.; Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 15-MAR-2001; Project End 31-JAN-2004 Summary: Intensive therapy is essential to optimize glucose control in insulindependent diabetes mellitus (IDDM). However, avoiding hypolglycemia is a major challenge for the management of IDDM. The central nervous system monitors glucose levels and coordinates a counter regulatory response during periods of hypoglycemia. However, the mechanism(s) and central pathways that underlie the counter regulatory response are not understood. Our preliminary findings suggest central glucagon-like peptide 1 (GLP-1) systems regulate sympathetic outflow and are involved in regulating CNS responses to insulin-induced hypoglycemia. We hypothesis that the action of GLP1 systems are fundamental in the coordinated endocrine and autonomic counter regulatory responses during hypoglycemia. In this proposal, we outline experiments designed to characterize the neuroanatomic mechanisms by which leptin and serotonin systems interact to regulate food intake. First, we will determine the effect of peripheral and central injections of GLP-1R agonists and antagonists on activating the sympathoadrenal and blood pressure responses. Next, using retrograde tracing and in situ hybridization, we will determine if subpopulations of GLP-1 sensitive neurons in hypothalamus and brainstem innervate sympathetic preganglionic neurons in the interomedial lateral cell column in the (IML) spinal cord. Third, using micro injections into selected brain regions, we will determine the sites in the brain that respond to GLP1 resulting in increased blood pressure and activation of adrenal catecholamine secretion. Fourth, using central injections of GLP-1 receptor antagonists we will determine the effect of central antagonism of GLP-1Rs on the counter regulatory responses to hypoglycemia. Finally, using GLP-1R-/- mice and mine over expressing GLP-1 receptor agonists, we will determine the effects on the coordinated counter
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regulatory responses following insulin-induced hypoglycemia in GLP-1R knockout mice and EXN-4 over expressing transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CENTRAL VISCEROSENSORY CIRCUITS-STRUCTURE AND FUNCTION Principal Investigator & Institution: Rinaman, Linda M.; Associate Professor; Neuroscience; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 01-APR-1999; Project End 31-MAR-2009 Summary: (provided by applicant): Sensory signals from within the body are delivered to brain regions that shape physiological and behavioral responses to stress and influence emotional learning. The research proposed in this R01 competing renewal application will provide new insights into the functional organization and development of viscerosensory inputs to the hypothalamus and limbic forebrain, with a focus on sensory signals from the gut. Experiments will test mechanistic hypotheses about the structure and function of noradrenergic (NA) and glucagon-like peptide-1 (GLP-1) signaling pathways that originate in the dorsal vagal complex (DVC) and target the paraventricular nucleus of the hypothalamus (PVN), lateral hypothalamic area (LHA), bed nucleus of the stria terminalis (BNST), and central nucleus of the amygdala (CeA). Hypotheses to be tested are organized into three Specific Aims. Aim 1 will use anterograde transneuronal virus tracing to label viscerosensory pathways from the stomach to the forebrain. One set of experiments will test the hypothesis that NA and non-NA DVC neurons relay gastric viscerosensory signals to discrete subregions of the PVN, LHA, BNST, and CeA. Other experiments will test the hypothesis that gastric viscerosensory inputs to the forebrain undergo significant structural maturation in rats during the first two weeks postnatal. Aim 2 will determine the necessity of DVC NA neurons for hypothalamic and limbic forebrain responses to interoceptive stress. One study will test the hypothesis that DVC NA neurons are necessary for certain interoceptive stressors [i.e., cholecystokinin (CCK), lithium chloride (LiCl), and lipopolysaccharide (LPS)] to inhibit food intake, but are unnecessary for these stressors to support conditioned taste aversion learning. A related study will test the hypothesis that DVC NA neurons are necessary for CCK, LiCl and LPS to induce cFos expression in the PVN and LHA, but are unnecessary for these stressors to induce cFos expression in the CeA. A third study will test the hypothesis that the ability of systemic CCK, LiCl, and LPS to activate cFos expression in the PVN, LHA, BNST, and CeA emerges gradually in rats during the first two weeks postnatal. Aim 3 will use electron microscopy to determine whether separate populations of NA and GLP-1-positive axon terminals converge on common postsynaptic targets in the PVN, LHA, CeA, and BNST. Experimental outcomes will advance our understanding of how viscerosensory inputs to the hypothalamus and limbic forebrain might impact diverse conditions such as anxiety disorders, visceral malaise, dysregulation of the HPA stress axis, depression, and conditioned aversions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHOLESTEROL ABSORPTION RATES IN NORMAL SUBJECTS AGED 17-80 Principal Investigator & Institution: Bosner, Matthew S.; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130
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Timing: Fiscal Year 2002 Summary: Cholesterol absorption was measured in 94 normal subjects aged 17-80 while consuming diets low in cholesterol (mean intake=226(126 mg/day). A new dual stable isotope method was used in which 15 mg cholesterol tracer with 6 additional mass units ([26,26,26,27,27,27--2H6]cholesterol) was given intravenously and 30 mg of another tracer with 5 additional mass units ([2,2,4,4,6-2H5]cholesterol or [23,24,25,26,2713C5]cholesterol) was given orally during a test meal. The ratio of tracers in plasma was determined by negative ion mass spectrometry of pentafluorobenzoyl sterol esters. Absorption values ranged from 29.0% to 80.1% (mean 56.2(12.1). Cholesterol absorption was increased in African-Americans (63.4(11.8% vs. 55.1(11.9%, p=0.027) but was similar for women (53.3(11.9%) and men (57.6(12.1%). It was not related to plasma lipoproteins, age, apo-E genotype, or chronic dietary intake of energy, fat, or cholesterol quantitated from food records. The amount of dietar y choleste rol absorbed was positively correlated with fasting plasma insulin (r=0.525, p20 years). It is estimated that the diagnosed number of NIDDM patients reflects only about 50% of the actual population suffering from NIDDM. However, it is recognized that only a limited percentage of this group requires improved treatment. The remainder of the NIDDM population generally self manages the disease though careful meal planning and exercise, or by means of oral hypoglycemic agents. Web site: http://www.delphion.com/details?pn=US06572542__
Patent Applications on Glucagon 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 glucagon: •
Analogues of GLP-1 Inventor(s): Dong, Zheng Xin; (Holliston, MA) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20040018981 Date filed: July 28, 2003 Abstract: The present invention is directed to peptide analogues of glucagon-like peptide-1, the pharmaceutically-acceptable salts thereof, to methods of using such analogues to treat mammals and to pharmaceutical compositions useful therefor comprising said analogues.
9
This has been a common practice outside the United States prior to December 2000.
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Excerpt(s): This application is a national phase application filed under 35 U.S.C. 371 of International Application No. PCT/EP99/09660, filed Dec. 7, 1999, which claims the benefit of U.S. application Ser. No. 60/111,255, filed Dec. 7, 1998, the contents of which are incorporated herein by reference. Glucagon-like peptide-1 (7-36) amide (GLP-1) (SEQ ID NO: 1) is synthesized in the intestinal L-cells by tissue-specific posttranslational processing of the glucagon precursor preproglucagon (Varndell, J. M., et al., J. Histochem Cytochem, 1985:33:1080-6) and is released into the circulation in response to a meal. The plasma concentration of GLP-1 rises from a fasting level of approximately 15 pmol/L to a peak postprandial level of 40 pmol/L. It has been demonstrated that, for a given rise in plasma glucose concentration, the increase in plasma insulin is approximately threefold greater when glucose is administered orally compared with intravenously (Kreymann, B., et al., Lancet 1987:2, 1300-4). This alimentary enhancement of insulin release, known as the incretin effect, is primarily humoral and GLP-1 is now thought to be the most potent physiological incretin in humans. In addition to the insulinotropic effect, GLP-1 suppresses glucagon secretion, delays gastric emptying (Wettergren A., et al., Dig Dis Sci 1993:38:665-73) and may enhance peripheral glucose disposal (D'Alessio, D. A. et al., J. Clin Invest 1994:93:22936). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Bicyclic oligopeptides Inventor(s): Mack, Juergen; (Biberach, DE), Maurer, Till; (Oberstadion, DE), Peters, Stefan; (Biberach, DE), Potterat, Olivier; (Mittelbiberach, DE), Streicher, Ruediger; (Biberach, DE), Wagner, Klaus; (Warthausen, DE) Correspondence: Boehringer Ingelheim Corporation; 900 Ridgebury Road; P. O. Box 368; Ridgefield; CT; 06877; US Patent Application Number: 20040072736 Date filed: July 17, 2003 Abstract: The invention relates to a bicyclic oligopeptide or ester thereof having the capability to inhibit the glucagon receptor, comprised of:(a) a first cyclic group, which comprises at least one cysteine group and is formed by an amide bonding of the Nterminal amino acid with the second carboxylate group of a diacid amino acid, and(b) a second cyclic group which is formed by an amide bonding of an amino acid with the.alpha.-carboxylate group of said diacid amino acid, and by a disulfide bonding of the C-terminal cysteine and a cysteine group within the first cyclic group (a); andto the use of such bicyclic oligopeptides for the preparation of a medicament for the treatment or prevention of diseases, in which glucagon receptors are involved. Excerpt(s): Benefit of U.S. Provisional Application Serial No. 60/416,797, filed on Oct. 8, 2002 is hereby claimed, and said Application is herein incorporated by reference. The invention relates to bicyclic oligopeptides or esters thereof which have the capability to inhibit the glucagon receptor. The U.S. Pat. No. 5,919,926 discloses bicyclic depsipeptides which are produced by fermentation of a specific marine actinomycete (CNB-091) in saltwater-based media. These bicyclic depsipeptides are taught to be useful as anti-biotic and anti-inflammatory agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Patents 165
•
Chronic treatment regimen using glucagon-like insulinotropic peptides Inventor(s): Dodd, Steven Witt; (Zionsville, IN), Mace, Kenneth Francis; (Fishers, IN), Trautmann, Michael Ernst; (Hamburg, DE) Correspondence: Eli Lilly And Company; Patent Division; P.O. Box 6288; Indianapolis; IN; 46206-6288; US Patent Application Number: 20040053819 Date filed: June 10, 2003 Abstract: The present invention encompasses a method of treating a disease by maintaining chronic steady state serum levels of a GLP-1 compound within a specified range. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/255,251, filed Dec. 13, 2000, No. 60/295,655, filed Jun. 4, 2001 and No. 60/298,652 filed Jun. 15, 2001. The present invention relates to a chronic treatment regimen using glucagon-like insulinotropic peptides in pharmaceutical articles of manufacture and methods. The intestinal hormone glucagon-like peptide-1 (GLP-1) shows great promise as a treatment for type 2 diabetes due to its ability to stimulate insulin secretion, lower glucagon secretion, inhibit gastric emptying, enhance glucose utilization, and induce appetite suppression and weight loss. Further, pre-clinical studies suggest that GLP-1 may also act to prevent the.beta.-cell deterioration that occurs as the disease progresses. Perhaps the most salient characteristic of GLP-1 is its ability to stimulate insulin secretion without the associated risk of hypoglycemia that is often seen when using insulin therapy and some types of oral therapies. When blood glucose levels drop to a certain threshold level, GLP-1 is not active. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
•
Combination therapy using a dual PPAR-a/PPAR-y activator and a GLP-1 derivative for the treatment of metabolic syndrome and related diseases and disorders Inventor(s): Bury, Paul Stanley; (Kobenhavn, DK), Jeppesen, Lone; (Virum, DK), Mogensen, John Patrick; (Herlev, DK), Pettersson, Ingrid; (Frederiksberg, DK), Sauerberg, Per; (Farum, DK) Correspondence: Reza Green, ESQ.; Novo Nordisk Pharmaceuticals, INC.; 100 College Road West; Princeton; NJ; 08540; US Patent Application Number: 20030199451 Date filed: May 20, 2003 Abstract: The present invention relates to a pharmaceutical composition comprising a dual Peroxisome Proliferator-Activated Receptor-alpha/Peroxisome ProliferatorActivated Receptor-gama activator (PPAR-.alpha./PPAR-.gamma.- ) and a Glucagon Like Peptide-1 (GLP-1) derivative for treating, preventing and reducing the risk of developing Type 2 diabetes, insulin resistance, dyslipidemia, obesity, hypertension and other related diseases and disorders. Excerpt(s): This application is a continuation of application Ser. No. 09/771,217, having a filing date of Jan. 26, 2001, now issued U.S. Pat. No. ______, the contents of which are herein incorporated by reference in its entirety. The present invention relates to a pharmaceutical composition comprising a dual Peroxisome Proliferator-Activated Receptor-alpha/Peroxisome Proliferator-Activated Receptor-gama activator (PPAR-
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Glucagon
.alpha./PPAR-.gamma.) and a Glucagon Like Peptide-1 (GLP-1) derivative for treating, preventing and reducing the risk of developing Type 2 diabetes, insulin resistance, dyslipidemia, obesity, hypertension and other related diseases and disorders. Coronary artery disease (CAD) is the major cause of death in Type 2 diabetic and metabolic syndrome patients (i.e. patients that fall within the `deadly quartet` category of impaired glucose tolerance, insulin resistance, hypertriglyceridaemia and/or obesity). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Combinations comprising dipeptidylpeptidase-iv inhibitor Inventor(s): Balkan, Bork; (Madison, CT), Holmes, David Grenville; (Binningen, CH), Hughes, Thomas Edward; (Somerville, NJ), Villhauer, Edwin Bernard; (Morristown, NJ) Correspondence: Thomas Hoxie; Novartis, Patent And Trademark Department; One Health Plaza 430/2; East Hanover; NJ; 07936-1080; US Patent Application Number: 20030139434 Date filed: October 10, 2002 Abstract: The invention relates to a combination which comprises a DPP-IV inhibitor and at least one further antidiabetic compound, preferably selected from the group consisting of insulin signalling pathway modulators, like inhibitors of protein tyrosine phosphatases (PTPases), non-small molecule mimetic compounds and inhibitors of glutamine-fructose-6-phosphate amidotransferase (GFAT), compounds influencing a dysregulated hepatic glucose production, like inhibitors of glucose-6-phosphatase (G6Pase), inhibitors of fructose-1,6-bisphosphatase (F-1,6-BPase), inhibitors of glycogen phosphorylase (GP), glucagon receptor antagonists and inhibitors of phosphoenolpyruvate carboxykinase (PEPCK), pyruvate dehydrogenase kinase (PDHK) inhibitors, insulin sensitivity enhancers, insulin secretion enhancers,.alpha.-glucosidase inhibitors, inhibitors of gastric emptying, insulin, and.alpha.sub.2-adrenergic antagonists, for simultaneous, separate or sequential use in the prevention, delay of progression or treatment of conditions mediated by dipeptidylpeptidase-IV (DPP-IV), in particular diabetes, more especially type 2 diabetes mellitus, conditions of impaired glucose tolerance (IGT), conditions of impaired fasting plasma glucose, metabolic acidosis, ketosis, arthritis, obesity and osteoporosis; and the use of such combination for the cosmetic treatment of a mammal in order to effect a cosmetically beneficial loss of body weight. Excerpt(s): The invention relates to a combination, such as a combined preparation or pharmaceutical composition, respectively, which comprises a dipeptidylpeptidase-IV (DPP-IV) inhibitor and at least one further antidiabetic compound, preferably selected from the group consisting of insulin signalling pathway modulators, like inhibitors of protein tyrosine phosphatases (PTPases), non-small molecule mimetic compounds and inhibitors of glutamine-fructose-6-phosphate amidotransferase (GFAT), compounds influencing a dysregulated hepatic glucose production, like inhibitors of glucose-6phosphatase (G6Pase), inhibitors of fructose-1,6-bisphosphatase (F-1,6-BPase), inhibitors of glycogen phosphorylase (GP), glucagon receptor antagonists and inhibitors of phosphoenolpyruvate carboxykinase (PEPCK), pyruvate dehydrogenase kinase (PDHK) inhibitors, insulin sensitivity enhancers, insulin secretion enhancers,.alpha.-glucosidase inhibitors, inhibitors of gastric emptying, insulin, and a.sub.2-adrenergic antagonists, for simultaneous, separate or sequential use, especially in the prevention, delay of progression or treatment of conditions mediated by dipeptidylpeptidase-IV (DPP-IV), in particular diabetes, more particular type 2 diabetes mellitus, conditions of impaired
Patents 167
glucose tolerance (IGT), conditions of impaired fasting plasma glucose, metabolic acidosis, ketosis, arthritis, obesity and osteoporosis; the use of such combination for the preparation of a pharmaceutical preparation for the prevention, delay of progression or treatment of such conditions; the use of such combination for the cosmetic treatment of a mammal in order to effect a cosmetically beneficial loss of body weight; a method of prevention, delay of progression or treatment of conditions mediated by DPP-IV; a method of improving the bodily appearance of a warm-blooded animal. DPP-IV is responsible for inactivating GLP-1. More particularly, DPP-IV generates a GLP-1 receptor antagonist and thereby shortens the physiological response to GLP-1. GLP-1 is a major stimulator of pancreatic insulin secretion and has direct beneficial effects on glucose disposal. Non-insulin dependent diabetes mellitus (type 2 diabetes mellitus) is characterized by both increased peripheral insulin resistance and abnormal insulin secretion. At least three abnormalities of insulin secretion are recognized: in the first phase, insulin secretion is lost and in the second phase insulin is both delayed and inadequate in the face of elevated circulating glucose levels. Several metabolic, hormonal, and pharmacological entities are known to stimulate insulin secretion including glucose, amino-acids and gastrointestinal peptides. The Diabetes Control and Complications Trial (DCCT) has established that lowering of blood glucose is associated with decreases in the onset and progression of diabetic microvascular complications (Diabetes Control and Complications Trial Research Group; N. Engl. J. Med. 1993, 329, 977-986). IGT is an impairment of glucose homeostasis closely related to type 2 diabetes mellitus. Both conditions convey a great risk of macrovascular disease. Therefore, one therapeutic focus is on optimizing and potentially normalizing glycemic control in subjects with type 2 diabetes mellitus, conditions of impaired fasting plasma glucose, or IGT. Presently available agents need to be improved in order to better meet this therapeutic challenge. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Crystallisation of a GLP-1 analogue Inventor(s): Arentsen, Anne Charlotte; (Holte, DK) Correspondence: Steve T. Zelson, ESQ.; Novo Nordisk OF North America, INC.; Suite 6400; 405 Lexington Avenue; New York; NY; 10174-6400; US Patent Application Number: 20030186858 Date filed: January 25, 2001 Abstract: Crystals of glucagon-like peptide-1 (GLP-1) and GLP-1 analogues, and processes for preparation of crystals of GLP-1 and GLP-1 analogues. Excerpt(s): The present invention relates to novel crystals of GLP-1 and analogues thereof, such as needle shaped crystals, and processes for the preparation of crystals of GLP-1 and analogues thereof. The hormones regulating insulin secretion belong to the so-called enteroinsular axis, designating a group of hormones, released from the gastrointestinal mucosa in response to the presence and absorption of nutrients in the gut, which promote an early and potentiated release of insulin. The enhancing effect on insulin secretion, the so-called incretin effect, is probably essential for a normal glucose tolerance. Many of the gastrointestinal hormones, including gastrin and secretin (cholecystokinin is not insulinotropic in man), are insulinotropic, but the only physiologically important ones, those that are responsible for the incretin effect, are the glucose-dependent insulinotropic polypeptide, GIP, and glucagon-like peptide-1(GLP1). Because of its insulinotropic effect, GIP, isolated in 1973 (1) immediately attracted
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considerable interest among diabetologists. However, numerous investigations carried out during the following years clearly indicated that a defective secretion of GIP was not involved in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) or noninsulin-dependent diabetes mellitus (NIDDM) (2). Furthermore, as an insulinotropic hormone, GIP was found to be almost ineffective in NIDDM (2). The other incretin hormone, GLP-1 is the most potent insulinotropic substance known (3). Unlike GIP, it is surprisingly effective in stimulating insulin secretion in NIDDM patients. In addition, and in contrast to the other insulinotropic hormones (perhaps with the exception of secretin) it also potently inhibits glucagon secretion. Because of these actions it has pronounced blood glucose lowering effects particularly in patients with NIDDM. Human GLP-1 is a 37 amino acid residue peptide originating from preproglucagon which is synthesised i.a. in the L-cells in the distal ileum, in the pancreas and in the brain. Processing of preproglucagon to give GLP-1(7-36)amide, GLP-1(7-37) and GLP-2 occurs mainly in the L-cells. A simple system is used to describe fragments and analogues of this peptide. Thus, for example, Gly.sup.8-GLP-1(7-37) designates a fragment of GLP-1 formally derived from GLP-1 by deleting the amino acid residues Nos. 1 to 6 and substituting the naturally occurring amino acid residue in position 8 (Ala) by Gly. Similarly, Lys.sup.34(N.sup.epsilon.- -tetradecanoyl)-GLP-1(7-37) designates GLP-1(7-37) wherein the.epsilon.-amino group of the Lys residue in position 34 has been tetradecanoylated. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cyanothiophene derivatives, compositions containing such compounds and methods of use Inventor(s): Campbell, Elizabeth Louise; (North Brunswick, NJ), Chapman, Kevin T.; (Scotch Plains, NJ), Duffy, Joseph L.; (Cranford, NJ), Kirk, Brian A.; (Basking Ridge, NJ), Konteatis, Zenon; (Chatham Township, NJ), Liang, Rui; (East Brunswick, NJ), Tata, James R.; (Westfield, NJ) Correspondence: Merck And CO Inc; P O Box 2000; Rahway; NJ; 070650907 Patent Application Number: 20040097552 Date filed: November 4, 2003 Abstract: The present invention addresses substituted cyanothiophene derivatives of the formula I: 1as well as compositions containing such compounds and methods of treatment. The compounds in the present invention are glucagon antagonists. The compounds block the action of glucagon at its receptor and thereby decrease the levels of plasma glucose providing a treatment of diabetes. Excerpt(s): The present invention is related to U.S. provisional application Serial No. 60/423,812, filed Nov. 3, 2002, the contents of which are hereby incorporated by reference. The present invention relates to substituted cyanothiophene derivatives, compositions containing such compounds and methods of treating type 2 diabetes mellitus. Diabetes refers to a disease process derived from multiple causative factors and is characterized by elevated levels of plasma glucose (hyperglycemia) in the fasting state or following glucose administration during an oral glucose tolerance test. Frank diabetes mellitus (e.g., a blood glucose level.gtoreq.126 mg/dL in a fasting state) is associated with increased and premature cardiovascular morbidity and mortality, and is related directly and indirectly to various metabolic conditions, including alterations of lipid, lipoprotein and apolipoprotein metabolism.
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Effects of glucagon-like peptide-1 (7-36) on antro-pyloro-duodenal motility Inventor(s): Goeke, Burkhard; (Gauting, DE), Schirra, Joerg; (Kirchhain, DE) Correspondence: Arnold & Porter; Attn: IP Docketing Department, Room 1126b; 555 Twelfth Street, NW; Washington; DC; 20004-1206; US Patent Application Number: 20030216292 Date filed: June 9, 2003 Abstract: The present invention provides an effective method for inhibiting antroduodenal motility in healthy subjects and patients suffering from various disorders, without the side effects associated with other pharmaceutical compositions. GLP-1 slows antro-duodenal motility and may be used for the treatment or prevention of gastrointestinal disorders such as diarrhea, postoperative dumping syndrome and irritable bowel syndrome, and also premedication in endoscopic procedures. Excerpt(s): The present invention relates to inhibiting antro-duodenal motility with GLP-1 and methods to alleviate discomfort during endoscopy and to alleviate symptoms of gastrointestinal disorders. Glucagon has been widely used to cause a variable reduction in gastroduodenal motility. The effect of glucagon appears to be dose-dependent with a minimally effective dose being 0.5 mg. Glucagon, however, does not facilitate colonoscopic evaluation (Norfleet, Gastrointest. Endosc., 24, 164-5, 1978), and at doses as high as 2 mg glucagon does not reduce contractions in the antrum (Gregerson et al., Scand. J. Gastroenterol. 23 (Supp 152), 42-47 (1988)). Furthermore, glucagon is contraindicated in persons with diabetes (Paul & Freyschmidt, ROFO Rortschr. Geb. Rontgenstr. Nuklearmed., 125, 31-7 (1996)), is expensive and its efficacy has been questioned. Side effects associated with the use of glucagon include nausea and vomiting. The effects are dose-dependent and can appear at a dose of 1 mg (Larsen et al., Scand. J. Gastroenterol. 21, 634-640, 1986; Gregersen et al., supra, Diamant Handbook Experimental Pharm, Lefevre ed., Vol. 66/2, 611-643, 1983). As dosages required to sufficiently reduce motility frequently exceed 1 mg, side effects from glucagon use are common. Such side effects render the patient extremely uncomfortable and often cause the endoscopic procedure to be interrupted or aborted. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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GLP-1 Fusion Proteins Inventor(s): Glaesner, Wolfgang; (Indianapolis, IN), Micanovic, Radmila; (Indianapolis, IN), Tschang, Sheng-Hung Rainbow; (Carmel, IN) Correspondence: Eli Lilly And Company; Patent Division; P.O. Box 6288; Indianapolis; IN; 46206-6288; US Patent Application Number: 20040053370 Date filed: May 29, 2003 Abstract: The present invention relates to glucagon-like-1 compounds fused to proteins that have the effect of extending the in vivo half-life of the peptides. These fusion proteins can be used to treat non-insulin dependent diabetes mellitus as well as a variety of other conditions.
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Excerpt(s): The present invention relates to glucagon-like peptides including analogs and derivatives thereof fused to proteins that have the effect of extending the in vivo half-life of the peptides. These fusion proteins can be used to treat non-insulin dependent diabetes mellitus as well as a variety of other conditions. Glucagon-Like Peptide 1 (GLP-1) is a 37 amino acid peptide that is secreted by the L-cells of the intestine in response to food ingestion. It has been found to stimulate insulin secretion (insulinotropic action), thereby causing glucose uptake by cells and decreased serum glucose levels [see, e.g., Mojsov, S., (1992) Int. J. Peptide Protein Research, 40:333-343]. However, GLP-1 is poorly active. A subsequent endogenous cleavage between the 6.sup.th and 7.sup.th position produces a more potent biologically active GLP-1(737)OH peptide. Numerous GLP-1 analogs and derivatives are known and are referred to herein as "GLP-1 compounds." These GLP-1 analogs include the Exendins which are peptides found in the venom of the GILA-monster. The Exendins have sequence homology to native GLP-1 and can bind the GLP-1 receptor and initiate the signal transduction cascade responsible for the numerous activities that have been attributed to GLP-1(7-37)OH. GLP-1 compounds have a variety of physiologically significant activities. For example, GLP-1 has been shown to stimulate insulin release, lower glucagon secretion, inhibit gastric emptying, and enhance glucose utilization. [Nauck, M. A., et al. (1993) Diabetologia 36:741-744; Gutniak, M., et al. (1992) New England J. of Med. 326:1316-1322; Nauck, M. A., et al., (1993) J. Clin. Invest. 91:301-307]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Glucagon antagonists/inverse agonists Inventor(s): Behrens, Carsten; (Kobenhavn N, DK), Lau, Jesper; (Farum, DK), Madsen, Peter; (Bagsvaerd, DK) Correspondence: Reza Green, ESQ.; Novo Nordisk OF North America, INC.; Suite 6400; 405 Lexington Avenue; New York; NY; 10174-6400; US Patent Application Number: 20030203946 Date filed: May 17, 2002 Abstract: A novel class of compounds, which act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor the compounds may be suitable for the treatment and/or prevention of any diseases and disorders, wherein a glucagon antagonistic action is beneficial, such as hyperglycemia, Type 1 diabetes, Type 2 diabetes, disorders of the lipid metabolism and obesity. Excerpt(s): The present invention relates to agents that act to antagonize the action of the glucagon peptide hormone on the glucagon receptor. More particularly, it relates to glucagon antagonists or inverse agonists. Glucagon is a key hormonal agent that, in cooperation with insulin, mediates homeostatic regulation of the amount of glucose in the blood. Glucagon primarily acts by stimulating certain cells (mostly liver cells) to release glucose when blood glucose levels fall. The action of glucagon is opposite to that of insulin, which stimulates cells to take up and store glucose whenever blood glucose levels rise. Both glucagon and insulin are peptide hormones. Glucagon is produced in the alpha islet cells of the pancreas and insulin in the beta islet cells. Diabetes mellitus is a common disorder of glucose metabolism. The disease is characterized by hyperglycemia and may be classified as Type 1 diabetes, the insulin-dependent form, or Type 2 diabetes, which is non-insulin-dependent in character. Subjects with Type 1 diabetes are hyperglycemic and hypoinsulinemic, and the conventional treatment for
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this form of the disease is to provide insulin. However, in some patients with Type 1 or Type 2 diabetes, absolute or relative elevated glucagon levels have been shown to contribute to the hyperglycemic state. Both in healthy control animals as well as in animal models of Type 1 and Type 2 diabetes, removal of circulating glucagon with selective and specific antibodies has resulted in reduction of the glycemic level (Brand et al., Diabetologia 37, 985 (1994); Diabetes 43, [suppl 1], 172A (1994); Am. J. Physiol. 269, E469-E477 (1995); Diabetes 44 [suppl 1], 134A (1995); Diabetes 45, 1076 (1996)). These studies suggest that glucagon suppression or an action that antagonizes glucagon could be a useful adjunct to conventional treatment of hyperglycemia in diabetic patients. The action of glucagon can be suppressed by providing an antagonist or an inverse agonist, ie substances that inhibit or prevent glucagon-induced responses. The antagonist can be peptidic or non-peptidic in nature. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Glucagon-like peptide-2 analogs Inventor(s): Crivici, Anna E.; (San Diego, CA), Drucker, Daniel J.; (Toronto, CA), Sumner Smith, Martin; (Bolton, CA) Correspondence: Foley And Lardner; Suite 500; 3000 K Street NW; Washington; DC; 20007; US Patent Application Number: 20030162703 Date filed: November 14, 2002 Abstract: Analogs of glucagon-like peptide 2, a product of glucagon gene expression, have been identified as intestinal tissue growth factors. Their formulation as pharmaceutical, and therapeutic use in treating disorders of the small bowel, are described. Excerpt(s): This application is a continuation-in-part of application Ser. No. 08/631,273, filed Apr. 12, 1996, and application Ser. No. 08/632,533, filed Apr. 12, 1996, and a continuation-in-part of application Ser. No. 08/422,540, filed Apr. 14, 1995, the disclosures of which are incorporated by reference herein. This invention relates to glucagon-related peptides having intestinal tissue growth promoting properties, and to their use therapeutically to treat various medical conditions resulting from the impaired growth or loss of such tissue. Expression of the glucagon gene yields a tissuedetermined variety of peptide products that are processed from the 160 residue proglucagon product. The organization of these peptides within the proglucagon precursor was elucidated by the molecular cloning of preproglucagon cDNAs from the rat, hamster and bovine pancreas. These analyses revealed that preproglucagon contains not only the sequence of glucagon and glicentin, but also two additional glucagon-like peptides (GLP-1 and GLP-2) separated from glucagon and each other by two spacer or intervening peptides (IP-I and IP-II). These peptides are flanked by pairs of basic amino acids, characteristic of classic prohormone cleavage sites, suggesting they might be liberated after posttranslational processing of proglucagon (Drucker, Pancreas, V1990, 5(4):484). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions Inventor(s): Bastos, Margarita M.; (Plainsboro, NJ), Bernatowicz, Michael; (Princeton, NJ), Ewing, William R.; (Yardley, PA), Lee, Ving; (Hamilton, NJ), Mapelli, Claudio; (Plainsboro, NJ), Natarajan, Sesha Iyer; (Hillsborough, NJ) Correspondence: Stephen B. Davis; Bristol-Myers Squibb Company; Patent Department; P O Box 4000; Princeton; NJ; 08543-4000; US Patent Application Number: 20030195157 Date filed: October 18, 2002 Abstract: The present invention provides novel human glucagon-like peptide-1 (GLP-1) peptide mimics that mimic the biological activity of the native GLP-1 peptide and thus are useful for the treatment or prevention of diseases or disorders associated with GLP activity. Further, the present invention provides novel, chemically modified peptides that not only stimulate insulin secretion in type II diabetics, but also produce other beneficial insulinotropic responses. These synthetic peptide GLP-1 mimics exhibit increased stability to proteolytic cleavage making them ideal therapeutic candidates for oral or parenteral administration. Excerpt(s): This application claims the benefit of provisional application U.S. Serial No. 60/342,015, filed Oct. 18, 2001, the disclosure of which is hereby incorporated by reference herein in its entirety. The present invention provides novel human glucagonlike peptide-1 (GLP-1) peptide mimics, which duplicate the biological activity of the native peptide, exhibit increased stability to proteolytic cleavage as compared to GLP-1 native sequences, and thus are useful for the amelioration of the diabetic condition. GLP-1 is an important gut hormone with regulatory function in glucose metabolism and gastrointestinal secretion and metabolism. Human GLP-1 is a 30 amino acid residue peptide originating from preproglucagon, which is synthesized for example, in the Lcells in the distal ileum, in the pancreas and in the brain. Processing of preproglucagon to yield GLP-1(7-36)amide and GLP-2 occurs mainly in the L-cells. GLP-1 is normally secreted in response to food intake, in particular carbohydrates and lipids stimulate GLP-1 secretion. GLP-1 has been identified as a very potent and efficacious stimulator for insulin release. GLP-1 lowers glucagon concentration, slows gastric emptying, stimulates insulin biosynthesis and enhances insulin sensitivity (Nauck, 1997, Horm. Metab.Res. 47:1253-1258). GLP-1 also enhances the ability of the B-cells to sense and respond to glucose in subjects with impaired glucose tolerance (Byrne, Eur. J. Clin. Invest., 28:72-78, 1998). The insulinotropic effect of GLP-1 in humans increases the rate of glucose metabolism partly due to increased insulin levels and partly due to enhanced insulin sensitivity (D'Alessio, Eur. J. Clin. Invest., 28:72-78, 1994). The above stated pharmacological properties of GLP-1 make it a highly desirable therapeutic agent for the treatment of type-II diabetes. Additionally, recent studies have shown that infusions of slightly supraphysiological amounts of GLP-1 significantly enhance satiety and reduce food intake in normal subjects (Flint, A., Raben, A., Astrup, A. and Holst, J. J., J.Clin.Invest, 101:515-520, 1998; Gutswiller, J. P., Goke, B., Drewe, J., Hildebrand, P., Ketterer, S., Handschin, D., Winterhaider, R., Conen, D and Beglinger, C. Gut 44:81-86, 1999;). The effect on food intake and satiety has also been reported to be preserved in obese subjects (Naslund, E., Barkeling, B., King, N., Gutniak, M., Blundell, J. E., Holst ,J. J., Rossner, S., and Hellstrom, P. M., Int. J. Obes. Relat. Metab. Disord., 23:304-311, 1999). In the above-cited studies a pronounced effect of GLP-1 on gastric emptying was also suspected to occur. Gastric emptying results in post-prandial glucose excursions. It has also been shown that in addition to stimulation of insulin secretion, GLP-1 stimulates
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the expression of the transcription factor IDX-1 while stimulating B-cell neogenesis and may thereby be an effective treatment and/or preventive agent for diabetes (Stoffers, D. A., Kieffer, T. J. Hussain, M. A.,Drucker, D. J., Bonner-Weir, S., Habener, J. F. and Egan, J. M. Diabetes, 40:741-748, 2000). GLP-1 has also been shown to inhibit gastric acid secretion (Wettergren, A., Schjoldager, B., Mortensen, P. E., Myhre, J., Christiansen, J., Holst, J. J., Dig. Dis. Sci., 38:665-673, 1993), which may provide protection against gastric ulcers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Long lasting synthetic glucagon like peptide (GLP-1) Inventor(s): Bridon, Dominique P.; (Ville Mont-Royal, CA), Ezrin, Alan M.; (Moraga, CA), Holmes, Darren L.; (Montreal, CA), L'Archeveque, Benoit; (Laval, CA), Leblanc, Anouk; (Montreal, CA), St. Pierre, Serge; (Ile Bizard, CA) Correspondence: Morrison & Foerster Llp; 425 Market Street; San Francisco; CA; 941052482; US Patent Application Number: 20040127398 Date filed: November 25, 2003 Abstract: Modified insulinotropic peptides are disclosed. The modified insulinotropic peptides are capable of forming a peptidase stabilized insulinotropic peptide. The modified insulinotropic peptides are capable of forming covalent bonds with one or more blood components to form a conjugate. The conjugates may be formed in vivo or ex vivo. The modified peptides are administered to treat humans with diabetes and other related diseases. Excerpt(s): This invention relates to modified insulinotropic peptides. In particular, this invention relates to modified glucagon like peptides and exendin peptides with long duration of action for the treatment of diabetes and other insulinotropic peptide related diseases, gastrointestinal function and activities associated with glucagon levels. The insulinotropic peptide hormone glucagon-like peptide (GLP-1) has been implicated as a possible therapeutic agent for the management of type 2 non-insulin-dependent diabetes mellitus as well as related metabolic disorders, such as obesity. Other useful insulinotropic peptides include exendin 3 and exendin 4. While useful, GLP-1, exendin 3 and exendin 4 suffer from limited duration of action associated with short plasma halflifes in vivo, mainly due to rapid serum clearance and proteolytic degradation. The enzyme responsible for the degradation of GLP-1, dipeptidyl peptidase IV, has been identified. Extensive work has been done in attempts to inhibit the peptidase or to modify GLP-1 in such a way that its degradation is slowed down while still maintaining biological activity. Despite these extensive efforts, a long lasting, active GLP-1 has not been produced. As such, the diabetic community has a tremendous need for improved GLP-1, exendin 3 and exendin 4 peptides. There is thus a need to modify GLP-1, exendin 3, exendin 4 and other insulinotropic peptides to provide longer duration of action in vivo, while maintaining their low toxicity and therapeutic advantages. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method and apparatus for real-time estimation and control of physiological parameters Inventor(s): Salganicoff, Marcos; (Philadelphia, PA) Correspondence: IP Department OF Piper Rudnick Llp; 3400 Two Logan Square; 18th And Arch Streets; Philadelphia; PA; 19103; US Patent Application Number: 20040034295 Date filed: March 18, 2003 Abstract: A real-time glucose estimator uses a linearized Kalman filter to determine a best estimate of glucose level in real time. The real-time glucose estimator receives at least one measurement corresponding to glucose level. The measurement can be obtained with one or more sensors and is provided to the linearized Kalman filter in real time. The linearized Kalman filter has dynamic models and executes a recursive routine to determine the best estimate of glucose level based upon the measurement. Additional information can be provided to the linearized Kalman filter for initialization, configuration, and the like. Outputs of the linearized Kalman filter can be provided to a patient health monitor for display or for statistical testing to determine status of the realtime glucose estimator. The real-time glucose estimator can be implemented using a software algorithm. A real-time controller operating as an artificial pancreas uses a Kalman control algorithm to control glucose level of a patient in real time. The real-time controller receives an estimate of the patien: glucose level and a reference glucose level. The estimate of the patient glucose level can be provided by an optimal estimator implemented using a linearized Kalman filter. The estimated glucose level and the reference glucose level are processed by the Kalman control algorithm to determine a control command in real time. The Kalman control algorithm has a dynamic process forced by the control command a cost function determining a relative level of control. The control command is provided to a dispenser which secretes insulin or glucagon in response to the control command to correct a relatively high glucose level or a relatively low glucose level. Excerpt(s): A portion of the disclosure of this patent document contains material that is subject to copyright protection. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or of the patent disclosure as it appears in the Patent and Trademark Office patent files or records, but otherwise reserves all copyright rights whatsoever. This present invention relates generally to a method and apparatus for estimating and controlling physiological parameters and more particularly to an optimal estimator and an optimal controller for estimating and controlling glucose levels in a patient. Different types of sensors (e.g., optical sensors) are available for monitoring of physiological parameters (e.g., glucose concentration). Glucose monitoring is typically performed by people with diabetes mellitus which is a medical condition involving a body's inability to produce the quantity or quality of insulin needed to maintain a normal circulating blood glucose. Frequent monitoring of glucose is generally necessary to provide effective treatment and to prevent long term complications of diabetes (e.g., blindness, kidney failure, heart failure, etc.). New methods of monitoring glucose are fast, painless and convenient alternatives to the typical capillary blood glucose (CBG) measurements which involve finger pricks that are painful, inconvenient and difficult to perform for long term. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods of enhancing functioning of the large intestine Inventor(s): Drucker, Daniel J.; (Ontario, CA) Correspondence: Stephen A. Bent; Foley & Lardner; Washington Harbour; 3000 K Street, N.W., Suite 500; Washington; DC; 20007-5143; US Patent Application Number: 20030207809 Date filed: April 21, 2003 Abstract: The invention relates to glucagon-related peptides and their use for the prevention or treatment of disorders involving the large intestine. In particular, it has now been demonstrated that GLP-2 and peptidic agonists of GLP-2 can cause proliferation of the tissue of large intestine. Thus, the invention provides methods of proliferating the large intestine in a subject in need thereof. Further, the methods of the invention are useful to treat or prevent inflammatory conditions of the large intestine, including inflammatory bowel diseases. Excerpt(s): This invention relates to glucagon-related peptides and their use for the prevention or treatment of disorders involving the large intestine. Glucagon-like peptide-2 (GLP-2) is a 33 amino acid peptide expressed in a tissue-specific manner from the pleiotropic glucagon gene. GLP-2 shows remarkable homology in terms of amino acid sequence to glucagon and Glucagon-like peptide-1 (GLP-1). Further, different mammalian forms of GLP-2 are highly conserved. For example, the human GLP-2 (hGLP-2) and degu (a south American rodent) GLP-2 differ from rat GLP-2 (rGLP-2) by one and three amino acids respectively. When given exogenously, GLP-2 can produce a marked increase in the proliferation of small intestinal epithelium of the test mice, apparently with no undesirable side effects (Drucker et al., 1996, PNAS:USA, 93:79117916). Subsequently it was shown that peptide analogs of native GLP-2 with certain modifications to the peptide sequence possess enhanced intestinotrophic activity at the small intestine (see co-pending application U.S. Ser. No. 08/669,791, incorporated herein by reference). Moreover, GLP-2 has also been shown to increase D-Glucose maximal transport rate across the intestinal basolateral membrane [Cheeseman and Tseng, 1996, American Journal of Physiology 271:G477-G482]. The invention is based, in part, on the discovery that GLP-2 receptor agonists act to enhance functioning of the large intestine. It is accordingly a general object of the present invention to exploit GLP-2 receptor agonists for therapeutic and related purposes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Peptides acting as both GLP-1 receptor agonists and glucagon receptor antagonists and their pharmacological methods of use Inventor(s): Clairmont, Kevin B.; (Cheshire, CT), Pan, Clark; (Castro Valley, CA), Whelan, James; (Madison, CT) Correspondence: Jeffrey M. Greenman; Bayer Pharmaceuticals Corporation; 400 Morgan Lane; West Haven; CT; 06516; US Patent Application Number: 20040002442 Date filed: January 16, 2003 Abstract: The invention provides polypeptides that act both as an agonist of the GLP-1 receptor and an antagonist of the glucagon receptor. Such polypeptides are useful for treating individuals with type 2 diabetes or other metabolic disorders.
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Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 10/265,345, filed Oct. 3, 2002. This invention relates to newly identified polypeptides that act both as an agonist of the GLP-1 receptor and an antagonist of the glucagon receptor and the use of such polypeptides for therapeutic purposes. More particularly, polypeptides of the present invention are useful in stimulating the release of insulin from pancreatic beta cells in a glucose-dependent manner and reducing glucagon-mediated secretion of glucose from the liver, thereby providing a treatment option for those individuals afflicted with a metabolic disorder such as diabetes, hyperglycemia, impaired fasting glucose, impaired glucose tolerance, prediabetic states, and obesity. Diabetes is characterized by impaired insulin secretion manifesting itself among other things by an elevated blood glucose level in the diabetic patient. Underlying defects lead to a classification of diabetes into two major groups: type I diabetes (or insulin dependent diabetes mellitus, IDDM), which arises when patients lack insulin-producing beta-cells in their pancreatic glands, and type 2 diabetes (or non-insulin dependent diabetes mellitus, NIDDM), which occurs in patients with an impaired beta-cell insulin secretion and/or alterations in insulin action. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substance for treatment of non-insulin dependent diabetes mellitus, hypertension and/or the metabolic syndrome Inventor(s): Gregersen, Soren; (Ega, DK), Hermansen, Kjeld; (Ega, DK), Hoie, Lars H.; (Oslo, NO), Jeppesen, Per Bendix; (Ega, DK) Correspondence: Winston & Strawn; Patent Department; 1400 L Street, N.W.; Washington; DC; 20005-3502; US Patent Application Number: 20040081712 Date filed: July 31, 2003 Abstract: A substance including the chemical structures of bicyclo[3.2.1]octan or the chemical structures of kaurene for the use in a dietary supplementation or as a constituent in a medicament for the treatment of non-insulin dependent diabetes mellitus, hypertension and/or the metabolic syndrome. The unique chemical structures of bicyclo[3.2.1]octan alone or in a kaurene structure provides the substances, such as steviol, isosteviol and stevioside, with the capability of enhancing or potentiating the secretion of insulin in a plasma glucose dependent manner. The substances including these unique chemical structures also have the capability of reducing the glucagon concentration in the blood and/or lowering the blood pressure thereby providing a selfregulatory treatment system for non-insulin dependent diabetes mellitus and/or hypertension. In a combination drug which also comprise a soy protein, and/or fibre and/or at least one phytoestrogen these substances act synergistically and such combination drugs are highly useful both prophylacticly or directly in the treatment of the metabolic syndrome and obesity and has due to the self-regulatory effect a widespread applicability as a dietary supplementation. Excerpt(s): This application is a continuation of International application PCT/DK01/00523 filed Jul. 31, 2001, the entire content of which is expressly incorporated herein by reference thereto. The present invention relates to a new medicament for the treatment of non-insulin dependent diabetes mellitus, hypertension and/or the metabolic syndrome. The present invention further relates to soy protein, phytoestrogens and dietary fibres and compositions thereof in the combination with a substance including a bicyclo[3.2.1]octan of the structural formula I shown in claim 1
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and/or a kaurene structure of the structural formula II shown in claim 2 and suitable for preventing and/or treating type 2 diabetes and/or the metabolic syndrome. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of glucokinase activator in combination with a glucagon antagonist for treating type 2 diabetes Inventor(s): Lau, Jesper; (Farum, DK) Correspondence: Novo Nordisk Pharmaceuticals, INC.; 100 College Road West; Princeton; NJ; 08540; US Patent Application Number: 20030138416 Date filed: December 3, 2002 Abstract: The invention relates to the use of a combination of a glucokinase activator and a glucagon antagonist for the management, treatment, control, or adjunct treatment of diseases, where increasing glucokinase activity and inhibiting the activity of glucagon is beneficial, such as for management, treatment, control, or adjunct treatment of type 1 diabetes or type 2 diabetes. Excerpt(s): This invention relates to the use of a combination of a glucokinase activator and a glucagon antagonist for the management, treatment, control, or adjunct treatment of diseases, where increasing glucokinase activity and inhibiting the activity of glucagon is beneficial, such as for management, treatment, control, or adjunct treatment of type 1 diabetes or type 2 diabetes. Diabetes is characterised by an impaired glucose metabolism manifesting itself among other things by an elevated blood glucose level in the diabetic patients. Underlying defects lead to a classification of diabetes into two major groups: Type 1 diabetes, or insulin demanding diabetes mellitus (IDDM), which arises when patients lack,.beta.-cells producing insulin in their pancreatic glands, and type 2 diabetes, or non-insulin dependent diabetes mellitus (NIDDM), which occurs in patients with an impaired ,.beta.-cell function besides a range of other abnormalities. Type 1 diabetic patients are currently treated with insulin, while the majority of type 2 diabetic patients are treated either with sulphonylureas that stimulate ,.beta.-cell function or with agents that enhance the tissue sensitivity of the patients towards insulin or with insulin. Among the agents applied to enhance tissue sensitivity towards insulin, metformin is a representative example. 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 glucagon, 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 “glucagon” (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 glucagon.
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You can also use this procedure to view pending patent applications concerning glucagon. 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 GLUCAGON Overview This chapter provides bibliographic book references relating to glucagon. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on glucagon include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “glucagon” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on glucagon: •
Endocrine Physiology. 2nd ed Source: St. Louis, MO: Mosby, Inc. 2001. 270 p. Contact: Available from Harcourt Health Sciences. Foots Cray High Street, Sidcup, Kent DA14 5HP, United Kingdom. 020 8308 5700. Fax 020 8308 5702. E-mail:
[email protected]. PRICE: $32.95 plus shipping and handling. ISBN: 0323011284. Summary: This book explains how the endocrine system functions in health and disease. The book begins with a chapter that serves as an introduction to the endocrine system, focusing on the chemical nature of hormones and their mechanisms of action. This is followed by chapters that discuss the physiology of the anterior pituitary gland, the posterior pituitary gland, the thyroid gland, the adrenal gland, and the endocrine pancreas. Topics covered in the chapter on the pancreas include the structure and actions of insulin and glucagon; the characteristics of type 1 and type 2 diabetes; the symptoms, complications, and long term sequelae of diabetes; the use of sulfonylureas
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and biguanides in managing diabetes; and problems associated with diabetes management. Remaining chapters discuss endocrine regulation of calcium and phosphate metabolism, the male and female reproductive systems, and the endocrinology of pregnancy. A review of the material in each chapter is facilitated by inclusion of objectives, summary boxes, highlighted words, a list of key words and concepts, and a chapter summary. Each chapter also includes self study problems. 3 appendices. Numerous figures. 14 tables. Numerous references. •
Diabetes Travel Guide Source: Alexandria, VA: American Diabetes Association. 2000. 172 p. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $14.95 plus shipping and handling. ISBN: 1580400418. Summary: This book organizes the process of traveling for people who have diabetes. Chapter one focuses on preparing for a trip. Topics include researching one's destination; seeing one's health care provider prior to departure, carrying a letter from one's doctor; locating medical facilities at one's destination; taking one's medications along; and obtaining health insurance, passports, and visas. Chapter two explains how to pack clothing, diabetes supplies, snacks, and items for an emergency and offers tips for preventing foot infections and other complications from happening. Chapter three provides detailed guidelines for packing and using insulin, syringes, a blood glucose meter, test strips, ketone strips, and a glucagon kit. Other topics include adjusting insulin and an insulin pump for various time zone changes. Chapter four provides tips for packing and taking oral medications, handling time zone changes, dealing with meals and physical activity, and creating a diabetes survival kit. Chapter five provides guidelines for traveling by auto, airplane, or boat. Chapter six addresses the issue of eating well and exercising while away from home. Topics include dealing with time zone changes, deciding where and when to eat, following a meal plan, eating fast foods, and adjusting insulin or diabetes pill doses according to physical activity level. Chapter seven uses a question and answer format to provide tips for coping with illness while traveling. Topics include receiving immunizations prior to traveling if necessary; checking blood glucose and ketones during an illness; dealing with vomiting, diarrhea, colds, jet lag, and urinary tract or vaginal infections; avoiding constipation; preventing insulin pump site infections; and preparing for health care prior to traveling. Chapter eight explains how to plan for situations that may occur during overseas travel, outdoor trips, and scuba diving. 22 appendices. 6 tables.
•
Medications for the Treatment of Diabetes Source: Alexandria, VA: American Diabetes Association. 2000. 190 p. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $14.95 plus shipping and handling. ISBN: 1580400612. Summary: This book presents an overview of the medications used to treat patients who have type 1 or type 2 diabetes and provides an individual summary of each class of drug and its role in the treatment of diabetes. Chapter one discusses the use of insulin for type 1 diabetes. Topics include insulin sources; insulin pharmacology; insulin storage, mixing, and administration; insulin dosing regimens; insulin use in diabetic
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ketoacidosis, parenteral nutrition, and pump therapy and among pregnant women, infants, and children; and the role of glucagon in type 1 diabetes. Chapter two reviews the use of insulins, sulfonylureas, thiazolidinediones, meglitinides, biguanides, and alpha glucosidase inhibitors in the treatment of type 2 diabetes. These classes of medications are discussed in terms of mechanisms of action, efficacy of monotherapy and combination therapy, effects on lipid profiles, common side effects, contraindications for use, and patient adherence to the regimens. Chapters three through seven discuss sulfonylureas, alpha glucosidase inhibitors, glitazones, meglitinide products, and biguanides in terms of pharmacology, indications for use, dosing considerations, special populations, contraindications, warnings, precautions, adverse effects, drug interactions, and clinical effects. Chapter eight focuses on insulin use in type 2 diabetes and gestational diabetes. Topics include indications for use, rationale and strategies for oral agent insulin therapy, insulin monotherapy in type 2 diabetes, and intensive insulin therapy. Chapters nine and 10 examine the treatment of hypertension and hyperlipidemia in patients who have diabetes, focusing on the goals of treatment, nonpharmacological interventions, and pharmacological treatments. The final chapter describes some medications currently being studied that will possibly be approved to treat diabetes or its complications. 6 figures. 31 tables. Numerous references. •
Teenagers with Type 1 Diabetes: A Curriculum for Adolescents and Families Source: Alexandria, VA: American Diabetes Association. 2000. [31 p.]. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $39.95 plus shipping and handling. ISBN: 158040054X. Summary: This illustrated guide presents a curriculum, based on materials developed for use in the Adolescent Clinic Project, that provides adolescents who have diabetes with a model for making decisions that affect both their lives and their diabetes and teaches adolescents to use problem solving skills to make adjustments to their treatment program based on the results of their blood glucose monitoring. The book is organized into five modules. The first module provides some information about making choices. The second module introduces all of the basic ideas and tools involved in diabetes care. The remaining three modules focus on special issues of decision making and adjusting diabetes treatment plans, including adjusting insulin dosage, planning meals, and exercising. Each module has five sections for health care professionals and two sections for adolescents. The professional sections present learning objectives, guidelines for teen and parent groups, a prequiz, and a postquiz. The adolescent sections provide an overview of the module and its goals and present module information. A final section provides guidelines that can be used with each of the modules. Each guideline offers ideas on special situations such as handling sick days, treating hypoglycemia, using glucagon, getting better results using blood sugar testing, keeping track of blood sugar and insulin, making permanent insulin dose changes, counting carbohydrates, choosing fast foods, determining a target heart rate, selecting exercise snacks, and decreasing insulin dose for extended exercise.
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Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “glucagon” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “glucagon” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “glucagon” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Current Views on Hypoglycemia and Glucagon by Italy) European Symposium on Hypoglycemia 1979 Rome, et al; ISBN: 0120586800; http://www.amazon.com/exec/obidos/ASIN/0120586800/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “glucagon” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:10 •
Hemodynamic effects of glucagon: an experimental study in the dog. Author: Sten Tibblin; Year: 1970
•
Regulation of glucagon biosynthesis and secretion in isolated mammalian pancreatic islets. Author: by Claes-Göran Oestenson; Year: 1979
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Studies on the effect of somatostatin and somatostatin analogs on insulin and glucagon secretion in man and rats: implications for clinical medicine. Author: by PerEric Lins; Year: 1980
Chapters on Glucagon In order to find chapters that specifically relate to glucagon, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and glucagon 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 “glucagon” (or 10
In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on glucagon: •
Antidiabetic Agents and Glucagon Source: in Moreau, D., ed. Nursing96 Drug Handbook. Springhouse, PA: Nursing96 Books. Springhouse Corporation. 1996. p. 748-763. Contact: Available from Springhouse Publishing. 1111 Bethlehem Pike, P.O. Box 908, Springhouse, PA 19477. (800) 331-3170 or (215) 646-4670 or (215) 646-4671. Fax (215) 6468716. PRICE: $29.95. ISBN: 087434817X. ISSN: 0273320X. Summary: This chapter on antidiabetic agents and glucagon is from a nursing handbook on pharmaceuticals. The handbook is designed to provide the nursing profession with drug information that focuses on what nurses need to know by emphasizing the clinical aspects of drug therapy. The chapter begins with an alphabetically-arranged list of the generic names of drugs described in the chapter; this is immediately followed by an alphabetized list of its brand names. This is then followed by a list of selected combination products in which these drugs are found. Information on each drug is arranged under the following headings: How Supplied, Action, Onset, Peak, Duration, Indications and Dosage, Adverse Reactions, Interactions, Contraindications, and Nursing Considerations. Drugs include acetohexamide; chlorpropamide; glipizide; glucagon; glyburide; insulins; metformin hydrochloride; tolazamide; tolbutamide.
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CHAPTER 7. PERIODICALS AND NEWS ON GLUCAGON Overview In this chapter, we suggest a number of news sources and present various periodicals that cover glucagon.
News Services and Press Releases One of the simplest ways of tracking press releases on glucagon 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 “glucagon” (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 glucagon. 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 “glucagon” (or synonyms). The following was recently listed in this archive for glucagon: •
Mini-dose subQ glucagon rescue effective in children with type 1 diabetes Source: Reuters Industry Breifing Date: May 09, 2001
•
Islet beta-cells appear to suppress output of glucagon from alpha cells Source: Reuters Medical News Date: March 14, 2003
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “glucagon” (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 “glucagon” (or synonyms). If you know the name of a company that is relevant to glucagon, 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 “glucagon” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly
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to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “glucagon” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on glucagon: •
Glucagon to the Rescue Source: Diabetes Advisor. 7(5): 30. September-October 1999. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article provides people who have diabetes with information on using glucagon to counter a low glucose reaction. Glucagon is a hormone that raises blood glucose levels by causing glucose stored in the liver to be broken down. A glucagon kit contains a syringe and a vial of glucagon crystals. Glucagon should be used only when a reaction is so severe that the person who has diabetes cannot treat himself or herself. People who control their diabetes with diet and exercise or with pills do not need a glucagon kit because they are unlikely to have bad low glucose reactions. However, people who take insulin should have a glucagon kit. The article provides guidelines for using glucagon to treat a person who has a low blood glucose reaction.
Academic Periodicals covering Glucagon Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to glucagon. In addition to these sources, you can search for articles covering glucagon 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 8. 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 glucagon. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with glucagon. 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 glucagon: Glucagon •
Systemic - U.S. Brands: Glucagon Diagnostic Kit; Glucagon Emergency Kit; Glucagon Emergency Kit for Low Blood Sugar http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202261.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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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 Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 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:13 •
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
12
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). 13 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 Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “glucagon” (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 27552 134 41 9 116 27852
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “glucagon” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
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 Biologists19 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.20 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.21 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/.
19 Adapted 20
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. 21 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 glucagon 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 glucagon. 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 glucagon. 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 “glucagon”:
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Diabetes http://www.nlm.nih.gov/medlineplus/diabetes.html Diabetic Diet http://www.nlm.nih.gov/medlineplus/diabeticdiet.html Islet Cell Transplantation http://www.nlm.nih.gov/medlineplus/isletcelltransplantation.html Juvenile Diabetes http://www.nlm.nih.gov/medlineplus/juvenilediabetes.html Pancreatic Diseases http://www.nlm.nih.gov/medlineplus/pancreaticdiseases.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on glucagon. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Recognizing and Treating Low Blood Sugar Source: Minneapolis, MN: International Diabetes Center. 1994. 11 p. Contact: Available from International Diabetes Center. Attention: IDC Publishing, 3800 Park Nicollet Boulevard, Minneapolis, MN 55416. (612) 993-3874. PRICE: $1.95. ISBN: 1885115059. Summary: This booklet reviews the basics of recognizing and treating low blood glucose, or hypoglycemia. Sections address recognition of hypoglycemia, including symptoms, pseudo-hypoglycemia, and hypoglycemic unawareness; treatment, including carbohydrate, glucose gels, and glucagon; and prevention, including blood glucose testing (SMBG), exercise, schedule changes, and precautions for drivers. The authors conclude by reiterating the importance of continual preparedness for hypoglycemic reactions and remind readers of the importance of medical alert identification. One chart lists the levels of hypoglycemia and the symptoms and recommended treatment for each level.
•
How to Recognize and Manage Hypoglycemia in Diabetes Source: Consultant. 36(11): 2363-2364. November 1996.
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Contact: Reprints available from Consultant Health Guide. Cliggott Publishing Company, 55 Holly Hill Lane, Box 4010, Greenwich, CT 06831-0010. Fax (203) 661-8163. Summary: This health guide is designed to give people with diabetes a basic overview of how to recognize and manage hypoglycemia (low blood glucose levels). The article describes the symptoms of hypoglycemia, including feeling shaky, anxious, and hungry; experiencing confusion or loss of consciousness; or having a seizure. The article also recommends treating symptoms of hypoglycemia with a sufficient amount of carbohydrate, such as that in glucose tablets, fruit juice, or skim milk. The article also describes the use of glucagon kits, used by a friend or family member if the person with diabetes becomes unconscious from hypoglycemia. The article concludes with a note about automobile driving for people who experience hypoglycemia; the author reminds readers that the only way hypoglycemia is likely to cause a death is if it occurs while the person with diabetes is driving. The article includes blank space for the provider to individualize patient instructions before giving a copy of the article to the patient. •
You Are Not Alone: Diabetes Organizer Source: Bridgeton, MO: You Are Not Alone, Inc. 1997. (information package). Contact: Available from You Are Not Alone, Inc. P.O. Box 940, Bridgeton, MO 63044. (314) 298-9872 or (314) 739-5672. PRICE: $49.95. Summary: This information package is designed to provide practical information to people with diabetes. The package consists of a three-ring binder enclosing a video, an information booklet, and various other aids to diabetes management. The spiral-bound booklet with tabbed dividers addresses the following topics: diabetes types, long term complications, blood glucose testing, insulin and other medications, preparing to draw insulin, drawing up a single type of insulin, mixing two types of insulin, where to inject insulin, hypoglycemia (low blood glucose) and hyperglycemia (high blood glucose), checking for ketones, sick day guidelines, glucagon, and nutrition basics. The booklet notes that blood glucose testing provides immediate results that can be used to make decisions about insulin adjustments; to understand the effects of various foods, exercise, and stress; and to manage periods of illness. Colorful pictures and sidebars are included throughout the booklet. A video addresses the emotional aspects of diabetes, the importance of preparing for emergencies, and followup health care provider visits. The video also provides tips for organizing diabetes information and supplies and offers an explanation of nutrition by a registered dietitian. The information package also includes a magnetized meal plan chart and a pen, an outing checklist pad, and a contact magnet designed for recording important telephone numbers. (AA-M).
•
Getting Started With Exercise Source: Indianapolis, IN: Eli Lilly and Company. 1994. 9 p. Contact: Available from Eli Lilly and Company. Lilly Corporate Center, Indianapolis, IN 46285. (800) 545-5979 or (317) 276-2000. PRICE: Single copy free. Summary: This patient education brochure reminds readers of the importance of exercise in diabetes management. After some basic facts about the impact of exercise on one's blood glucose and other body systems, the brochure discusses the necessity for a medical checkup before starting an exercise program; choosing the right exercise; calories burned during common aerobic activities; starting an exercise program with walking; exercise goals; and recommendations for before, during, and after exercise with regards to diabetes control, blood glucose levels, and insulin needs. The brochure
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also includes product insert information for glucagon for injection, a product manufactured by Eli Lilly and Company. 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 glucagon. 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
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to glucagon. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with glucagon. 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 glucagon. 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.
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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 “glucagon” (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 “glucagon”. 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 “glucagon” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “glucagon” (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.22
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
22
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)23: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
23
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
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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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
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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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/
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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
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
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 glucagon: •
Basic Guidelines for Glucagon Glucagon Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003716.htm Glucagonoma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000326.htm
•
Signs & Symptoms for Glucagon Erythema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm Skin lesion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm
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Skin rash Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm •
Diagnostics and Tests for Glucagon Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm Fasting glucose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003482.htm Glucagon Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003716.htm Glucose tolerance test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003466.htm Lactate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003507.htm Serum glucagon Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003716.htm Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm
•
Nutrition for Glucagon Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm
•
Background Topics for Glucagon Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Amino acids Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002222.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm
Online Glossaries 213
Endocrine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002351.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Metastasis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002260.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
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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GLUCAGON DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetohexamide: A sulfonylurea hypoglycemic agent that is metabolized in the liver to 1hydrohexamide. [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] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Actin: Essential component of the cell skeleton. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinomas: A malignant tumor of the epithelial cells of a gland which typically metastasizes by way of the lymphatics. [NIH]
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Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [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 Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [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 Antagonists: Drugs that bind to but do not activate adrenergic receptors. Adrenergic antagonists block the actions of the endogenous adrenergic transmitters epinephrine and norepinephrine. [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] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH]
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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] Airways: Tubes that carry air into and out of the lungs. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldose Reductase Inhibitor: A class of drugs being studied as a way to prevent eye and nerve damage in people with diabetes. Aldose reductase is an enzyme that is normally present in the eye and in many other parts of the body. It helps change glucose (sugar) into a sugar alcohol called sorbitol. Too much sorbitol trapped in eye and nerve cells can damage these cells, leading to retinopathy and neuropathy. Drugs that prevent or slow (inhibit) the action of aldose reductase are being studied as a way to prevent or delay these complications of diabetes. [NIH] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] 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] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] 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 Cell: A type of cell in the pancreas (in areas called the islets of Langerhans). Alpha cells make and release a hormone called glucagon, which raises the level of glucose (sugar) in the blood. [NIH]
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Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [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] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ammonium Chloride: An acidifying agent that is used as an expectorant and a diuretic. [NIH]
Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [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] Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU]
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Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
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] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] 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] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]
Anovulation: Suspension or cessation of ovulation in animals and humans. [NIH]
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Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]
Anterograde: Moving or extending forward; called also antegrade. [EU] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] 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] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antidiabetic Agent: A substance that helps a person with diabetes control the level of glucose (sugar) in the blood so that the body works as it should. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the
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maturation and proliferation of malignant cells. [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] Antispasmodic: An agent that relieves spasm. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [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] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] 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] Arcuate Nucleus: A nucleus located in the middle hypothalamus in the most ventral part of the third ventricle near the entrance of the infundibular recess. Its small cells are in close contact with the ependyma. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrestin: A 48-Kd protein of the outer segment of the retinal rods and a component of the phototransduction cascade. Arrestin quenches G-protein activation by binding to phosphorylated photolyzed rhodopsin. Arrestin causes experimental autoimmune uveitis when injected into laboratory animals. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU]
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Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Artificial Pancreas: A large machine used in hospitals that constantly measures glucose (sugar) in the blood and, in response, releases the right amount of insulin. Scientists are also working to develop a small unit that could be implanted in the body, functioning like a real pancreas. [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] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] 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] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [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] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH]
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Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Automobile Driving: The effect of environmental or physiological factors on the driver and driving ability. Included are driving fatigue, and the effect of drugs, disease, and physical disabilities on driving. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] 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] 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] Barium: An element of the alkaline earth group of metals. It has an atomic symbol Ba, atomic number 56, and atomic weight 138. All of its acid-soluble salts are poisonous. [NIH] Barium enema: A procedure in which a liquid with barium in it is put into the rectum and colon by way of the anus. Barium is a silver-white metallic compound that helps to show the image of the lower gastrointestinal tract on an x-ray. [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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Beta blocker: A drug used to slow the heart rate and reduce pressure inside blood vessels. It also can regulate heart rhythm. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile
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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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotic: Pertaining to living organisms in their ecological rather than their physiological relations. [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] Biphasic: Having two phases; having both a sporophytic and a gametophytic phase in the life cycle. [EU] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [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 Flow Velocity: A value equal to the total volume flow divided by the cross-sectional area of the vascular bed. [NIH]
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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 Viscosity: The internal resistance of the blood to shear forces. The in vitro measure of whole blood viscosity is of limited clinical utility because it bears little relationship to the actual viscosity within the circulation, but an increase in the viscosity of circulating blood can contribute to morbidity in patients suffering from disorders such as sickle cell anemia and polycythemia. [NIH] 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] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bombesin: A tetradecapeptide originally obtained from the skins of toads Bombina bombina and B. variegata. It is also an endogenous neurotransmitter in many animals including mammals. Bombesin affects vascular and other smooth muscle, gastric secretion, and renal circulation and function. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a
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neurotransmitter. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchopulmonary: Pertaining to the lungs and their air passages; both bronchial and pulmonary. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] 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] Calcium Chloride: A salt used to replenish calcium levels, as an acid-producing diuretic, and as an antidote for magnesium poisoning. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [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] 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
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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] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoid: A type of tumor usually found in the gastrointestinal system (most often in the appendix), and sometimes in the lungs or other sites. Carcinoid tumors are usually benign. [NIH]
Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspases: A family of intracellular cysteine endopeptidases. They play a key role in inflammation and mammalian apoptosis. They are specific for aspartic acid at the P1 position. They are divided into two classes based on the lengths of their N-terminal prodomains. Caspases-1,-2,-4,-5,-8, and -10 have long prodomains and -3,-6,-7,-9 have short prodomains. EC 3.4.22.-. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2. [NIH] Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissue. They function optimally within an acidic pH range. [NIH]
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Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [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] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [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 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 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] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage.
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Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Checkup: A general physical examination. [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] Chemotherapy: Treatment with anticancer drugs. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]
Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] 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] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH]
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Chronotropic: Affecting the time or rate, as the rate of contraction of the heart. [EU] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Chyme: A thick liquid made of partially digested food and stomach juices. This liquid is made in the stomach and moves into the small intestine for further digestion. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [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] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [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
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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] Colorectal: Having to do with the colon or the rectum. [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make
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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] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [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] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] 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] 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] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [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] 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
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discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that has ruptured and discharged its ovum. [NIH] 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] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] C-Peptide: A 31-amino acid peptide which connects the A and B chains of proinsulin. The exact composition of the peptide is species dependent. In beta cells proinsulin is enzymatically converted to insulin with the liberation of the C-peptide. An immunoassay has been developed for assessing pancreatic beta cell secretory function in diabetic patients in whom circulating insulin antibodies and exogenous insulin interfere with insulin immunoassay. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryofixation: Fixation of a tissue by localized cooling at very low temperature. [NIH]
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Cryopreservation: Preservation of cells, tissues, organs, or embryos by freezing. In histological preparations, cryopreservation or cryofixation is used to maintain the existing form, structure, and chemical composition of all the constituent elements of the specimens. [NIH]
Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] 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] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cystamine: A radiation-protective agent that interferes with sulfhydryl enzymes. It may also protect against carbon tetrachloride liver damage. [NIH] Cysteamine: A radiation-protective agent that oxidizes in air to form cystamine. It can be given intravenously or orally to treat radiation sickness. The bitartrate has been used for the oral treatment of nephropathic cystinosis. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cysteine Endopeptidases: Endopeptidases which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22. [NIH] Cysteinyl: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [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]
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] 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] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a
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course of action or an idea. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [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] 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] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] 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] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [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] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] 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.
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[NIH]
Dietitian: An expert in nutrition who helps people plan what and how much food to eat. [NIH]
Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dispenser: Glass, metal or plastic shell fitted with valve from which a pressurized formulation is dispensed; an instrument for atomizing. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [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] 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] Distention: The state of being distended or enlarged; the act of distending. [EU] Diuretic: A drug that increases the production of urine. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the
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relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [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] 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] Dumping Syndrome: Gastrointestinal nonfunctioning pylorus. [NIH]
symptoms
resulting
from
an
absent
or
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
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levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electroacupuncture: A form of acupuncture using low frequency electrically stimulated needles to produce analgesia and anesthesia and to treat disease. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emergency Medicine: A branch of medicine concerned with an individual's resuscitation, transportation and care from the point of injury or beginning of illness through the hospital or other emergency treatment facility. [NIH] Emergency Treatment: First aid or other immediate intervention for accidents or medical conditions requiring immediate care and treatment before definitive medical and surgical management can be procured. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue.
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[NIH]
Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [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] Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]
Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [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] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enema: The injection of a liquid through the anus into the large bowel. [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 Intake: Total number of calories taken in daily whether ingested or by parenteral
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routes. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] EnteroEnvironmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Ependyma: A thin membrane that lines the ventricles of the brain and the central canal of the spinal cord. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Varices: Stretched veins in the esophagus that occur when the liver is not working properly. If the veins burst, the bleeding can cause death. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH]
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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] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] 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] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [EU]
Expert Systems: Computer programs based on knowledge developed from consultation with experts on a problem, and the processing and/or formalizing of this knowledge using these programs in such a manner that the problems may be solved. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extreme obesity: A body mass index [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical,
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characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Febrile: Pertaining to or characterized by fever. [EU] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Feeding Behavior: Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals. [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] Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (heart/embryology) only on the basis of time. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flatus: Gas passed through the rectum. [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] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [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] Fructose-1,6-Diphosphatase Deficiency: An autosomal recessive fructose metabolism disorder due to absent or deficient fructose-1,6-diphosphatase activity. Gluconeogenesis is impaired, resulting in accumulation of gluconeogenic precursors (e.g., amino acids, lactate, ketones) and manifested as hypoglycemia, ketosis, and lactic acidosis. Episodes in the newborn infant are often lethal. Later episodes are often brought on by fasting and febrile infections. As patients age through early childhood, tolerance to fasting improves and development becomes normal. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy
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person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [NIH] Fura-2: A fluorescent calcium chelating agent which is used to study intracellular calcium in many tissues. The fluorescent and chelating properties of Fura-2 aid in the quantitation of endothelial cell injury, in monitoring ATP-dependent calcium uptake by membrane vesicles, and in the determination of the relationship between cytoplasmic free calcium and oxidase activation in rat neutrophils. [NIH] Fuzzy Logic: Approximate, quantitative reasoning that is concerned with the linguistic ambiguity which exists in natural or synthetic language. At its core are variables such as good, bad, and young as well as modifiers such as more, less, and very. These ordinary terms represent fuzzy sets in a particular problem. Fuzzy logic plays a key role in many medical expert systems. [NIH] Galanin: A neurotransmitter. [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] Gangliosides: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]
Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric 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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroduodenal: Pertaining to or communicating with the stomach and duodenum, as a gastroduodenal fistula. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal Hormones: Hormones secreted by the gastrointestinal mucosa that affect the timing or the quality of secretion of digestive enzymes, and regulate the motor activity of the digestive system organs. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as
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a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [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 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 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] Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [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] Gestational: Psychosis attributable to or occurring during pregnancy. [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] Glipizide: An oral hypoglycemic agent which is rapidly absorbed and completely metabolized. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glossitis: Inflammation of the tongue. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucagonoma: Glucagon-secreting tumor of the pancreatic alpha cells characterized by a distinctive rash, weight loss, stomatitis, glossitis, diabetes, hypoaminoacidemia, and normochromic normocytic anemia. [NIH]
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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] Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2. [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [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 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] Glucose-6-Phosphatase: An enzyme that catalyzes the conversion of D-glucose 6-phosphate and water to D-glucose and orthophosphate. EC 3.1.3.9. [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]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
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,
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sometimes with prominent cardiac involvement. [NIH] Glycogen Synthase: An enzyme that catalyzes the transfer of D-glucose from UDPglucose into 1,4-alpha-D-glucosyl chains. EC 2.4.1.11. [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] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] 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] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [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] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] 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] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH]
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Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [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] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hexokinase: An enzyme that catalyzes the conversion of ATP and a D-hexose to ADP and a D-hexose 6-phosphate. D-Glucose, D-mannose, D-fructose, sorbitol, and D-glucosamine can act as acceptors; ITP and dATP can act as donors. The liver isoenzyme has sometimes been called glucokinase. (From Enzyme Nomenclature, 1992) EC 2.7.1.1. [NIH] Hirudin: The active principle in the buccal gland secretion of leeches. It acts as an antithrombin and as an antithrombotic agent. [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] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH]
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Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]
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] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] 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] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] 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] Hyperopia: Farsightedness; ability to see distant objects more clearly than close objects; may be corrected with glasses or contact lenses. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH]
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Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [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] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [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 symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxic: Having too little oxygen. [NIH] Hysterosalpingography: Radiography of the uterus and fallopian tubes after the injection of a contrast medium. [NIH] Idiotype: The unique antigenic determinant in the variable region. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileum: The lower end of the small intestine. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [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 system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or
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immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impaction: The trapping of an object in a body passage. Examples are stones in the bile duct or hardened stool in the colon. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] 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] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH]
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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] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] 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] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which
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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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] 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] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH]
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Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] 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] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] Jet lag: Symptoms produced in human beings by fast travel through large meridian difference. [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] Keratinocyte growth factor: A substance that stimulates the growth of epithelial cells that line the surface of the mouth and intestinal tract. [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] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually
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associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue. [NIH] Kidney Transplantation: The transference of a kidney from one human or animal to another. [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] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] 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] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] 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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Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [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] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipolysis: The hydrolysis of lipids. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Lithium Chloride: A salt of lithium that has been used experimentally as an immunomodulator. [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 Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver metastases: Cancer that has spread from the original (primary) tumor to the liver. [NIH]
Liver Mitochondria: Yellow discoloration of the liver due to fatty degeneration of liver parenchymal cells; the cause may be chemical poisoning. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Living Donors: Non-cadaveric providers of organs for transplant to related or non-related recipients. [NIH]
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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] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Luminescence: The property of giving off light without emitting a corresponding degree of heat. It includes the luminescence of inorganic matter or the bioluminescence of human matter, invertebrates and other living organisms. For the luminescence of bacteria, bacterial luminescence is available. [NIH] 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] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by
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T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [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] 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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammogram: An x-ray of the breast. [NIH] Manic: Affected with mania. [EU] 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] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [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]
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Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic 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] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [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] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] 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
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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] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Evolution: Multiple rounds of selection, amplification, and mutation leading to molecules with the desired properties. [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] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] 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]
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Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Monounsaturated fat: An unsaturated fat that is found primarily in plant foods, including olive and canola oils. [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, water, inorganic salts, and exfoliated cells. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] 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] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] 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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle
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fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] 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] Nearsightedness: The common term for myopia. [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] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]
Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] 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.
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Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotensin: A biologically active tridecapeptide isolated from the hypothalamus. It has been shown to induce hypotension in the rat, to stimulate contraction of guinea pig ileum and rat uterus, and to cause relaxation of rat duodenum. There is also evidence that it acts as both a peripheral and a central nervous system neurotransmitter. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] 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] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [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
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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] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [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] Oligomenorrhea: Abnormally infrequent menstruation. [NIH] Oligopeptides: Peptides composed of between two and twelve amino acids. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [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] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum;
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lysomomes; plastids; and vacuoles. [NIH] Organogenesis: Clonal propagation which involves culturing explants from roots, leaves, or stems to form undifferentiated callus tissue; after the cells form shoots, they are separated and rooted. Alternatively, if the callus is put in liquid culture, somatic embryos form. [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] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] 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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [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]
Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreas Transplant: A surgical procedure that involves replacing the pancreas of a person who has diabetes with a healthy pancreas that can make insulin. The healthy pancreas comes from a donor who has just died or from a living relative. A person can donate half a pancreas and still live normally. [NIH] Pancreas Transplantation: The transference of a pancreas from one human or animal to another. [NIH] Pancreatectomy: Surgery to remove the pancreas. In a total pancreatectomy, a portion of the stomach, the duodenum, common bile duct, gallbladder, spleen, and nearby lymph nodes also are removed. [NIH]
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Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Hormones: Peptide hormones secreted into the blood by cells in the Islets of Langerhans of the pancreas. The alpha cells secrete glucagon; the beta cells secrete insulin; the delta cells secrete somatostatin; and the PP cells secrete pancreatic polypeptide. [NIH] Pancreatic Polypeptide: A 36-amino acid polypeptide with physiological regulatory functions. It is secreted by pancreatic tissue. Plasma pancreatic polypeptide increases after ingestion of food, with age, and in disease states. A lack of pancreatic polypeptide in the islets of Langerhans has been associated with the obese syndrome in rats and mice. [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] Paradoxical: Occurring at variance with the normal rule. [EU] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural 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]
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Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Peptide Library: A collection of cloned peptides, or chemically synthesized peptides, frequently consisting of all possible combinations of amino acids making up an n-amino acid peptide. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] 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] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [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] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage
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begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] 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] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] 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] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phosphodiesterase Inhibitors: Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] 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]
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Phosphorylase Phosphatase: An enzyme that deactivates glycogen phosphorylase a by releasing inorganic phosphate and phosphorylase b, the inactive form. EC 3.1.3.17. [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] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]
Piloerection: Involuntary erection or bristling of hairs. [NIH] 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] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] 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] 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]
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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]
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] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polycystic Ovary Syndrome: Clinical symptom complex characterized by oligomenorrhea or amenorrhea, anovulation, and regularly associated with bilateral polycystic ovaries. [NIH] 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] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyuria: Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [NIH] Portal Pressure: The venous pressure measured in the portal vein. [NIH] Portosystemic Shunt: An operation to create an opening between the portal vein and other veins around the liver. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH]
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Postprandial: Occurring after dinner, or after a meal; postcibal. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] 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] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [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] Proinsulin: The substance made first in the pancreas that is then made into insulin. When insulin is purified from the pancreas of pork or beef, all the proinsulin is not fully removed. When some people use these insulins, the proinsulin can cause the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the
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insulin is injected. The purified insulins have less proinsulin and other impurities than the other types of insulins. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] 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 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] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] 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] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein 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
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peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] 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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]
Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Purified Insulins: Insulins with much less of the impure proinsulin. It is thought that the use of purified insulins may help avoid or reduce some of the problems of people with diabetes such as allergic reactions. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic
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acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pylorus: The opening in a vertebrate from the stomach into the intestine. [EU] 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] Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40. [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] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU]
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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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] 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] Refractive Power: The ability of an object, such as the eye, to bend light as light passes through it. [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] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Renal Circulation: The circulation of the blood through the vessels of the kidney. [NIH] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH]
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Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Respiratory Therapy: Care of patients with deficiencies and abnormalities associated with the cardiopulmonary system. It includes the therapeutic use of medical gases and their administrative apparatus, environmental control systems, humidification, aerosols, ventilatory support, bronchopulmonary drainage and exercise, respiratory rehabilitation, assistance with cardiopulmonary resuscitation, and maintenance of natural, artificial, and mechanical airways. [NIH] Restitution: The restoration to a normal state. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH]
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Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] 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] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Satiation: Full gratification of a need or desire followed by a state of relative insensitivity to that particular need or desire. [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] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU]
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Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretin: A hormone made in the duodenum. Causes the stomach to make pepsin, the liver to make bile, and the pancreas to make a digestive juice. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Secretory Vesicles: Vesicles derived from the golgi apparatus containing material to be released at the cell surface. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Sella Turcica: A bony prominence situated on the upper surface of the body of the sphenoid bone. It houses the pituitary gland. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] 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] 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] 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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins
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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]
Short Bowel Syndrome: A malabsorption syndrome resulting from extensive operative resection of small bowel. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] 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] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several
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research applications. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spasmolytic: Checking spasms; antispasmodic. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] 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] 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] 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]
Standardize: To compare with or conform to a standard; to establish standards. [EU] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this
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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] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]
Stool: The waste matter discharged in a bowel movement; feces. [NIH] Streptozocin: An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals. [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] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] 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] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Superior Cervical Ganglion: The largest and uppermost of the paravertebral sympathetic ganglia. [NIH] Supplementation: Adding nutrients to the diet. [NIH]
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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] Supraventricular: Situated or occurring above the ventricles, especially in an atrium or atrioventricular node. [EU] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] 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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH]
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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] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Terminalis: A groove on the lateral surface of the right atrium. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [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] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyroiditis: Inflammation of the thyroid gland. [NIH] 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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH]
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Tolazamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of chlorpropamide. [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] 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] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Total pancreatectomy: Surgery to remove the entire pancreas. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] 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] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Traction: The act of pulling. [NIH] Tractus: A part of some structure, usually that part along which something passes. [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] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a
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protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trophic: Of or pertaining to nutrition. [EU] 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] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]
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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [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
Dictionary 285
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]
Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the 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] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] 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] Uterine Contraction: Contraction of the uterine muscle. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] 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] Vagal: Pertaining to the vagus nerve. [EU] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]
Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU]
286
Glucagon
Vasculitis: Inflammation of a blood vessel. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoactive Intestinal Peptide: A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Pressure: The blood pressure in a vein. It is usually measured to assess the filling pressure to the ventricle. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [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] Vial: A small bottle. [EU] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [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
Dictionary 287
tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] 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]
Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH]
288
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Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
289
INDEX A Abdomen, 215, 224, 225, 240, 252, 255, 265, 266, 279, 280, 285 Abdominal, 49, 95, 215, 216, 243, 252, 253, 264, 265, 266, 284 Abdominal Pain, 215, 243, 253, 284 Ablation, 38, 66, 215 Acceptor, 215, 264 Accommodation, 215, 260 Acetaminophen, 215, 243 Acetohexamide, 183, 215 Acetone, 215, 253 Acetylcholine, 215, 262 Acidity, 215, 267 Acidosis, 60, 215, 242, 253 Actin, 39, 215, 261 Adaptability, 215, 228 Adaptation, 22, 43, 49, 62, 63, 65, 99, 215 Adenine, 215, 216, 272 Adenocarcinomas, 102, 215 Adenosine, 71, 136, 216, 222, 267 Adenovirus, 54, 216 Adenylate Cyclase, 67, 71, 75, 78, 110, 133, 134, 142, 216, 242 Adipocytes, 18, 54, 216, 254 Adipose Tissue, 54, 57, 82, 216 Adjustment, 215, 216 Adjuvant, 216, 244 Adrenal Cortex, 216, 217, 233, 240, 248, 270 Adrenal Medulla, 84, 102, 216, 227, 240, 262 Adrenergic, 6, 34, 43, 48, 67, 76, 132, 166, 216, 220, 237, 240, 271, 281 Adrenergic Antagonists, 166, 216 Adverse Effect, 181, 216, 278 Aerobic, 201, 216, 259 Aerosol, 216, 281 Afferent, 49, 216, 254, 268 Affinity, 65, 73, 120, 132, 216, 217, 222, 258, 278 Affinity Chromatography, 132, 216 Agar, 217, 234 Age of Onset, 217, 284 Agonist, 39, 59, 98, 131, 155, 171, 175, 176, 217, 237 Airways, 217, 275 Alanine, 19, 21, 32, 33, 70, 76, 217
Albumin, 88, 217, 268 Aldose Reductase Inhibitor, 152, 217 Aldosterone, 141, 217 Algorithms, 217, 224 Alimentary, 118, 164, 217, 265 Alkaline, 215, 217, 218, 223, 226, 282 Alkaloid, 217, 222, 226, 230, 277 Allergen, 217, 235 Allylamine, 217, 218 Alpha Cell, 12, 50, 53, 61, 69, 185, 217, 244, 265 Alpha-1, 218, 267 Alternative medicine, 186, 218 Ameliorating, 43, 218 Amenorrhea, 218, 219, 269 Amine, 40, 218, 247 Amino acid, 19, 29, 33, 35, 43, 55, 59, 71, 73, 85, 91, 103, 116, 118, 141, 150, 153, 154, 155, 156, 158, 160, 164, 168, 170, 171, 172, 175, 212, 217, 218, 220, 221, 222, 233, 234, 242, 243, 245, 247, 248, 254, 258, 262, 263, 265, 266, 267, 269, 271, 272, 276, 277, 280, 282, 283, 284, 285 Amino Acid Sequence, 154, 175, 218, 220, 271 Amino-terminal, 79, 218 Ammonia, 218, 245, 281, 285 Ammonium Chloride, 142, 218 Amplification, 218, 259 Ampulla, 218, 229, 239 Amygdala, 14, 15, 62, 218, 255 Amyloid, 40, 218 Anabolic, 54, 218 Anaesthesia, 218, 251 Anal, 219, 256 Analgesic, 215, 219, 239 Analog, 4, 25, 219 Analogous, 160, 219, 237, 283 Analytes, 21, 219 Anaphylatoxins, 219, 231 Anatomical, 8, 24, 219, 222, 236, 250, 258, 261, 277 Anemia, 219, 225, 244, 273 Anesthesia, 219, 220, 238 Anesthetics, 219, 240 Aneurysm, 219, 286 Angina, 219, 271 Angina Pectoris, 219, 271
290
Glucagon
Anginal, 219, 262 Angiography, 117, 219 Animal model, 11, 35, 42, 45, 155, 171, 219 Anions, 217, 219, 252, 278 Anomalies, 161, 219, 282 Anorexia, 49, 62, 219, 243, 285 Anorexia Nervosa, 49, 62, 219 Anovulation, 219, 269 Antagonism, 13, 101, 220, 236 Antecedent, 25, 31, 220 Anterograde, 14, 220 Anti-Anxiety Agents, 220, 270 Antibacterial, 220, 279 Antibiotic, 220, 266, 270, 279, 280 Antibiotic Prophylaxis, 220, 270 Antibodies, 19, 68, 81, 104, 155, 171, 220, 221, 222, 233, 240, 246, 250, 256, 259, 268 Anticoagulant, 220, 271 Antidiabetic, 138, 152, 166, 183, 220, 245 Antidiabetic Agent, 152, 183, 220 Antidote, 220, 226 Antigen, 151, 216, 220, 221, 231, 240, 248, 250, 251, 257, 258, 273 Antigen-Antibody Complex, 220, 231 Antihypertensive, 220, 242 Anti-inflammatory, 29, 164, 215, 220, 245 Anti-Inflammatory Agents, 164, 220 Antimicrobial, 220, 235 Antineoplastic, 220, 244, 280, 286 Antiserum, 74, 136, 221 Antispasmodic, 122, 221, 277, 279 Antithrombotic, 221, 247 Antiviral, 221, 266 Anus, 219, 221, 223, 225, 231, 239 Anxiety, 14, 132, 220, 221, 271 Anxiety Disorders, 14, 221 Apolipoproteins, 221, 255 Apoptosis, 18, 26, 36, 41, 45, 50, 63, 65, 97, 98, 221, 227, 234 Applicability, 176, 221 Approximate, 9, 221, 243 Aqueous, 3, 162, 221, 227, 234, 254 Arachidonic Acid, 221, 271 Arcuate Nucleus, 36, 66, 221 Arginine, 50, 60, 68, 85, 89, 110, 123, 145, 154, 219, 221, 262 Arrestin, 48, 221 Arterial, 74, 109, 112, 144, 217, 221, 229, 233, 248, 272, 281 Arteries, 221, 225, 233, 256, 258, 260, 272 Arterioles, 221, 225, 226, 258 Arteriovenous, 12, 24, 221, 258
Artery, 166, 219, 221, 222, 233, 238, 272, 274 Artificial Pancreas, 7, 159, 174, 222 Aspartic, 222, 227, 239 Aspartic Acid, 222, 227 Assay, 7, 17, 20, 28, 60, 143, 222, 249, 273 Astrocytes, 222, 258, 259 Asymptomatic, 222, 265 ATP, 24, 38, 52, 57, 136, 216, 222, 236, 243, 244, 245, 246, 247, 252, 256, 267, 272, 273 Atrial, 222, 233, 284 Atrioventricular, 222, 233, 281 Atrioventricular Node, 222, 281 Atrium, 222, 233, 281, 282, 284, 286 Atrophy, 43, 63, 222 Atropine, 222, 277 Attenuated, 16, 222, 285 Attenuation, 16, 222 Autoantibodies, 19, 222 Autoantigens, 222 Autodigestion, 222, 265 Autoimmune disease, 50, 151, 222, 260 Autologous, 152, 223 Automobile Driving, 201, 223 Autonomic, 13, 22, 36, 81, 105, 215, 223, 262, 266, 281 Autonomic Nervous System, 223, 266, 281 B Bacteria, 220, 223, 224, 238, 239, 241, 242, 248, 256, 258, 259, 274, 277, 279, 283, 285 Bacterial Physiology, 215, 223 Bacteriophage, 223, 283 Barium, 81, 84, 122, 223 Barium enema, 84, 122, 223 Basement Membrane, 31, 223, 254 Benign, 223, 227, 246, 261, 273 Benzene, 223, 227 Beta blocker, 121, 223 Beta-pleated, 218, 223 Bewilderment, 223, 232 Bilateral, 223, 269 Bile, 16, 82, 223, 224, 234, 243, 247, 248, 250, 255, 277, 280 Bile Acids, 16, 223, 280 Bile Acids and Salts, 223 Bile duct, 224, 250 Biliary, 82, 107, 224, 229, 231, 247, 265 Biliary Tract, 224, 265 Bilirubin, 217, 224 Biological therapy, 224, 246 Bioluminescence, 224, 256 Biopsy, 224
291
Biosynthesis, 9, 11, 17, 34, 65, 172, 182, 221, 224, 242, 267, 271, 277 Biotechnology, 67, 78, 182, 186, 195, 224 Biotic, 164, 224 Biotransformation, 224 Biphasic, 7, 224 Bivalent, 224, 258 Bladder, 224, 250, 260, 271, 285 Blastocyst, 224, 232, 268 Bloating, 224, 253 Blood Coagulation, 224, 225, 226, 282 Blood Flow Velocity, 90, 224 Blood Platelets, 225, 277, 282 Blood pressure, 13, 112, 126, 176, 212, 220, 225, 227, 248, 249, 259, 262, 263, 269, 272, 278, 286 Blood Viscosity, 113, 225 Body Fluids, 225, 237, 242, 263, 278 Body Mass Index, 225, 241 Bolus, 37, 81, 114, 225 Bolus infusion, 225 Bombesin, 26, 62, 84, 225 Bone Marrow, 23, 223, 225, 234, 244, 256, 257, 260 Bone Marrow Transplantation, 23, 225 Bone scan, 225, 276 Bowel Movement, 225, 236, 280 Brachytherapy, 225, 252, 253, 273, 287 Bradykinin, 84, 225, 262, 268 Breeding, 54, 226 Bronchi, 226, 240, 241, 283 Bronchial, 226, 247 Bronchiseptica, 226, 266 Bronchopulmonary, 226, 275 Buccal, 226, 247, 256, 280 Bulimia, 49, 62, 226 C Calcification, 144, 226 Calcitonin, 111, 226 Calcium, 16, 24, 84, 96, 117, 132, 137, 180, 226, 231, 236, 243, 258, 262, 265, 282 Calcium channel blocker, 96, 226 Calcium Chloride, 132, 226 Callus, 226, 238, 264 Capillary, 31, 159, 174, 225, 226, 286 Capsaicin, 56, 226 Capsules, 226, 244 Carbohydrate, 4, 17, 38, 45, 57, 71, 126, 127, 132, 151, 153, 156, 161, 200, 201, 226, 245, 269 Carbon Dioxide, 161, 227, 234, 268, 275 Carcinogen, 40, 227
Carcinogenesis, 40, 227 Carcinogenic, 223, 227, 251, 271, 280 Carcinoid, 107, 227 Carcinoma, 17, 40, 227 Cardiac, 217, 227, 233, 240, 246, 260, 275, 280 Cardiopulmonary, 84, 227, 275 Cardioselective, 227, 271 Cardiovascular, 128, 144, 152, 154, 168, 227, 277, 286 Cardiovascular disease, 128, 144, 152, 154, 227 Carnitine, 95, 227 Carotene, 227, 275 Carrier Proteins, 227, 268, 273 Case report, 112, 227 Caspases, 41, 227 Catabolism, 10, 227 Catecholamine, 6, 13, 97, 227, 237 Catechols, 21, 227 Cathepsins, 141, 227 Catheters, 32, 228, 250, 252 Cathode, 228, 238 Cations, 9, 134, 228, 252 Caudal, 15, 49, 228, 235, 249, 269 Causal, 8, 228 Cause of Death, 16, 27, 166, 228 Cecum, 228, 254 Cell Adhesion, 12, 228 Cell Adhesion Molecules, 12, 228 Cell Cycle, 87, 228, 246 Cell Death, 26, 52, 221, 228, 261 Cell Differentiation, 46, 52, 228 Cell Division, 223, 228, 246, 257, 259, 268, 271, 277 Cell Lineage, 30, 51, 228 Cell membrane, 138, 139, 227, 228, 235, 252, 257, 267, 270 Cell Physiology, 60, 110, 228 Cell proliferation, 9, 12, 26, 63, 98, 142, 228 Cell Respiration, 228, 259, 275 Cell Survival, 10, 137, 228, 246 Cellobiose, 228, 229 Cellulose, 111, 229, 268 Cerebral, 127, 134, 229, 232, 240, 241, 279, 282 Cerebrospinal, 65, 229 Cerebrospinal fluid, 65, 229 Cerebrovascular, 227, 229 Cerebrum, 229 Cervix, 229, 275 Character, 155, 170, 219, 229, 235
292
Glucagon
Checkup, 201, 229 Chemotactic Factors, 229, 231 Chemotherapy, 137, 212, 229 Cholestasis, 16, 229 Cholesterol, 15, 133, 134, 223, 229, 230, 233, 237, 248, 255, 256, 280 Cholesterol Esters, 229, 255 Choroid, 57, 229, 275 Chromaffin System, 229, 239 Chromatin, 221, 229, 262 Chromosomal, 71, 218, 229 Chromosome, 11, 101, 107, 229, 255, 277 Chronic, 6, 8, 15, 45, 49, 53, 72, 85, 90, 112, 118, 121, 152, 165, 229, 230, 231, 239, 251, 253, 254, 256, 265, 269, 280, 281, 284, 285 Chronic renal, 118, 229, 269, 285 Chronotropic, 134, 137, 230 Chylomicrons, 230, 255 Chyme, 48, 230 Circadian, 75, 230 Circulatory system, 230, 239 Cirrhosis, 16, 23, 39, 94, 108, 116, 230, 269 CIS, 53, 230, 275 Clamp, 6, 24, 39, 92, 154, 230 Clathrin, 230, 239 Clear cell carcinoma, 230, 235 Cleave, 60, 230 Clinical Medicine, 182, 230, 270 Clinical trial, 5, 22, 28, 63, 195, 230, 234, 237, 272, 273 Cloning, 110, 150, 157, 171, 224, 230 Coated Vesicles, 230, 239 Cofactor, 230, 272, 282 Colchicine, 139, 140, 230, 284 Colitis, 230, 253 Collagen, 11, 218, 223, 230, 231, 243, 248, 268, 271 Collagen disease, 231, 248 Colloidal, 217, 231, 238, 278, 281 Colon, 65, 101, 119, 223, 230, 231, 250, 251, 253, 254, 284 Colorectal, 102, 231 Combinatorial, 59, 231 Common Bile Duct, 16, 231, 234, 264 Complement, 24, 219, 231, 244, 268 Complementary and alternative medicine, 131, 146, 231 Complementary medicine, 131, 231 Computational Biology, 195, 231 Computed tomography, 232, 276 Computer Simulation, 59, 232
Computerized axial tomography, 232, 276 Conception, 64, 232, 242 Concomitant, 5, 48, 61, 109, 232 Conduction, 40, 132, 222, 232 Cones, 232, 268, 275 Confusion, 201, 232, 236, 249, 285 Congestion, 232, 240 Connective Tissue, 225, 230, 231, 232, 243, 254, 256, 258, 276, 281 Consciousness, 201, 219, 220, 232, 236, 272, 275 Constipation, 180, 232, 253 Constitutional, 232, 260 Constriction, 232, 253, 286 Consultation, 19, 232, 241 Contractility, 53, 70, 108, 232 Contraindications, ii, 181, 183, 232 Contrast medium, 219, 232, 249 Conventional therapy, 232 Conventional treatment, 155, 170, 232 Convulsions, 232, 249 Coordination, 233, 260 Cor, 8, 27, 62, 66, 233, 271 Coronary, 107, 166, 219, 222, 227, 233, 258, 260 Coronary heart disease, 227, 233 Coronary Thrombosis, 233, 258, 260 Corpus, 233, 256, 266, 270, 287 Corpus Luteum, 233, 256, 270 Cortex, 233, 241 Cortical, 233, 241, 277 Corticotropin-Releasing Hormone, 8, 27, 233 Cortisol, 19, 21, 25, 32, 60, 90, 217, 233 C-Peptide, 18, 233 Crossing-over, 233, 274 Cryofixation, 233, 234 Cryopreservation, 104, 234 Crystallization, 161, 234 Culture Media, 18, 217, 234 Cultured cells, 34, 234 Curative, 23, 234, 282 Cyclic, 21, 38, 70, 74, 75, 77, 87, 127, 136, 144, 164, 216, 234, 242, 246, 262, 267, 268 Cyclosporine, 41, 234 Cystamine, 234 Cysteamine, 70, 234 Cysteine, 40, 164, 227, 234, 239 Cysteine Endopeptidases, 227, 234, 239 Cysteinyl, 234, 258 Cystic Duct, 231, 234 Cystine, 234
293
Cytokine, 66, 234 Cytoplasm, 7, 221, 228, 234, 239, 258, 260, 262, 276 Cytoskeleton, 234, 259 D Decarboxylation, 234, 247 Decidua, 234, 268 Decision Making, 181, 234 Degenerative, 235, 247, 275 Dehydration, 4, 235 Deletion, 65, 66, 71, 221, 235 Dendrites, 235, 261 Density, 119, 225, 235, 237, 255, 263, 269, 279 Deoxyribonucleic, 235, 276 Depolarization, 39, 41, 235 Depressive Disorder, 235, 255 Deprivation, 41, 235 DES, 127, 128, 219, 235 Desensitization, 48, 134, 235, 250 Detergents, 25, 235 Developmental Biology, 44, 235 Diabetic Ketoacidosis, 181, 235 Diagnostic procedure, 149, 186, 235 Diarrhea, 169, 180, 235, 253 Diarrhoea, 235, 243 Diastolic, 235, 248 Diencephalon, 235, 249 Dietary Fats, 235, 255 Dietitian, 201, 236 Diffusion, 236, 251, 252 Digestion, 26, 58, 217, 223, 224, 225, 230, 236, 252, 255, 280, 285 Digestive system, 53, 236, 243 Digestive tract, 236, 278 Dilatation, Pathologic, 236, 286 Dilation, 225, 236, 286 Diltiazem, 122, 132, 236 Dimerization, 34, 236 Direct, iii, 10, 18, 39, 51, 66, 69, 89, 167, 189, 230, 236, 237, 274, 281 Discrete, 14, 15, 37, 40, 77, 236 Disorientation, 232, 236 Dispenser, 159, 174, 236 Disposition, 49, 236 Dissociation, 134, 216, 236 Distal, 30, 40, 168, 172, 236, 253 Distention, 87, 236 Diuretic, 218, 226, 236, 278 DNA Topoisomerase, 236, 244 Dopamine, 237, 259, 262, 267 Dorsal, 14, 62, 237, 269
Dorsum, 237 Dose-dependent, 96, 169, 237 Double-blind, 22, 237 Drive, ii, vi, 11, 12, 31, 34, 39, 41, 54, 55, 125, 237, 252 Drug Design, 25, 66, 237 Drug Interactions, 181, 190, 237 Drug Tolerance, 237, 283 Duct, 218, 231, 237, 241, 257, 276 Dumping Syndrome, 169, 237 Duodenal Ulcer, 123, 237 Duodenum, 52, 223, 237, 239, 243, 253, 262, 264, 277, 280 Dyes, 218, 237, 262 Dyslipidemia, 165, 166, 237 E Eating Disorders, 49, 238 Effector, 8, 215, 231, 238, 267 Efficacy, 22, 31, 39, 63, 118, 169, 181, 237, 238 Elastin, 230, 238 Electroacupuncture, 127, 135, 238 Electrolysis, 219, 228, 238 Electrolyte, 63, 123, 217, 238, 242, 254, 263, 270, 278, 285 Electrons, 228, 238, 252, 264, 273 Electrophoresis, 48, 238 Electrophysiological, 9, 24, 238 Embolus, 238, 251 Embryo, 224, 228, 238, 251 Embryogenesis, 30, 238 Embryology, 238, 242 Emergency Medicine, 81, 97, 121, 122, 123, 238 Emergency Treatment, 238 Emollient, 238, 245 Encapsulated, 7, 238 Encephalopathy, 45, 239 Endocrine Glands, 239, 265 Endocrine System, 179, 239, 261 Endopeptidases, 227, 234, 239, 271 Endorphin, 82, 239 Endoscope, 239 Endoscopic, 169, 239 Endoscopy, 115, 118, 121, 169, 239 Endosomes, 141, 239 Endothelial cell, 239, 243, 282 Endothelium, 239, 262 Endothelium-derived, 239, 262 Endotoxic, 239, 255 Endotoxins, 231, 239 End-stage renal, 229, 239, 269
294
Glucagon
Enema, 239 Energy balance, 56, 239, 254 Energy Intake, 79, 112, 239 Enhancer, 44, 240 Enkephalin, 240, 271 Enterocolitis, 58, 240 Enteroglucagon, 84 Environmental Health, 194, 196, 240 Enzymatic, 17, 39, 113, 218, 226, 227, 231, 240, 247, 267, 275 Ependyma, 221, 240 Epidermal, 71, 73, 240 Epidermal Growth Factor, 73, 240 Epidermis, 240 Epigastric, 240, 264 Epithelial, 13, 26, 38, 51, 63, 137, 142, 215, 234, 240, 253, 254 Epithelial Cells, 13, 38, 51, 63, 215, 240, 253, 254 Epithelium, 44, 63, 175, 223, 239, 240 Epitopes, 68, 121, 155, 240 Erythema, 140, 211, 240 Erythrocytes, 219, 225, 240, 274 Esophageal, 81, 99, 121, 240 Esophageal Varices, 99, 240 Esophagus, 236, 240, 243, 280 Estradiol, 49, 240 Estrogen, 12, 241, 271 Ethanol, 241, 242 Ethnic Groups, 80, 241 Eukaryotic Cells, 241, 250, 263 Evacuation, 232, 241, 243 Evoke, 241, 280 Excipients, 160, 241 Excitation, 241, 262 Excitatory, 62, 241, 245 Excrete, 241, 253, 274 Exhaustion, 220, 241 Exocrine, 26, 30, 44, 51, 63, 241, 264 Exogenous, 8, 33, 39, 48, 52, 71, 224, 233, 239, 241, 271, 284 Expectorant, 218, 241 Expert Systems, 241, 243 Expiration, 241, 275 External-beam radiation, 241, 253, 273, 287 Extracellular, 25, 53, 62, 68, 105, 121, 218, 222, 232, 241, 278, 282 Extreme obesity, 54, 241 Eye Infections, 216, 241 F Fallopian tube, 241, 249, 275
Family Planning, 195, 241 Fat, 15, 48, 57, 116, 126, 133, 134, 138, 140, 216, 221, 224, 225, 227, 233, 238, 241, 253, 254, 255, 260, 276, 278, 284 Fatigue, 223, 241, 246 Febrile, 242 Feces, 232, 242, 280 Feeding Behavior, 20, 62, 242 Fermentation, 164, 242 Fetal Heart, 75, 242 Fetus, 12, 242, 268, 285 Filtration, 86, 242, 253 Fine-needle aspiration, 242, 261 Fistula, 242, 243 Flatus, 242, 243 Fluid Therapy, 242, 263 Fluorescence, 7, 24, 37, 64, 101, 242 Fold, 10, 242 Forearm, 225, 242 Forskolin, 54, 242 Fractionation, 151, 242 Freeze-dried, 161, 242 Fructose-1,6-Diphosphatase Deficiency, 96, 242 Fulminant Hepatic Failure, 94, 242 Fura-2, 39, 243 Fuzzy Logic, 163, 243 G Galanin, 62, 136, 243 Gallbladder, 215, 224, 234, 236, 243, 264 Ganglia, 23, 215, 243, 255, 261, 266, 280, 281 Gangliosides, 41, 243 Gas, 47, 158, 218, 227, 236, 242, 243, 248, 253, 262, 275, 280, 281 Gastric Acid, 48, 123, 173, 243 Gastric Emptying, 44, 104, 113, 164, 165, 166, 170, 172, 243 Gastric Inhibitory Polypeptide, 97, 102, 106, 118, 243 Gastrin, 11, 26, 76, 84, 85, 102, 104, 123, 141, 167, 243, 248 Gastroduodenal, 169, 243 Gastroenteritis, 3, 243 Gastroenterology, 48, 83, 86, 89, 108, 116, 119, 121, 123, 243 Gastrointestinal, 23, 26, 53, 56, 62, 63, 73, 92, 93, 94, 96, 99, 105, 115, 118, 120, 150, 153, 156, 158, 167, 169, 172, 173, 223, 225, 227, 237, 240, 241, 243, 277, 278, 280, 286
295
Gastrointestinal Hormones, 63, 93, 167, 243 Gastrointestinal tract, 23, 53, 62, 73, 105, 223, 241, 243, 277, 278 Gelatin, 11, 234, 243, 245, 281, 282 Gels, 200, 244 Gene Expression, 8, 9, 26, 35, 36, 51, 53, 54, 61, 63, 66, 71, 72, 76, 100, 131, 137, 157, 171, 244 Gene Therapy, 38, 92, 97, 216, 244 Genetic Engineering, 224, 230, 244 Genistein, 134, 244 Genotype, 15, 45, 244, 267 Germ Cells, 244, 257, 263, 264, 282 Gestation, 64, 244, 266, 268 Gestational, 100, 126, 152, 181, 244 Gland, 141, 179, 215, 216, 229, 244, 247, 256, 264, 265, 268, 271, 277, 280, 282 Glipizide, 183, 244 Glomerular, 143, 244, 253 Glomerulus, 244 Glossitis, 244 Glottis, 244, 267 Glucagonoma, 79, 117, 140, 211, 244 Glucocorticoid, 8, 55, 245, 248 Glucokinase, 35, 36, 177, 245, 247 Gluconeogenesis, 27, 29, 32, 33, 42, 47, 48, 54, 116, 153, 242, 245 Glucose Intolerance, 16, 235, 245 Glucose Tolerance Test, 38, 45, 117, 168, 245 Glucose-6-Phosphatase, 35, 166, 245 Glutamate, 50, 53, 245 Glutamic Acid, 13, 36, 245, 262, 271 Glutamine, 22, 33, 142, 166, 245 Glyburide, 121, 183, 245 Glycerol, 25, 33, 245, 267 Glycine, 102, 218, 223, 245, 262, 277 Glycogen, 34, 43, 47, 54, 57, 123, 138, 139, 166, 245, 246, 267, 268 Glycogen Storage Disease, 34, 123, 245 Glycogen Synthase, 34, 138, 139, 246 Glycolysis, 60, 143, 246 Glycoprotein, 246, 254, 282, 284 Glycosidic, 228, 246, 267 Gout, 230, 246 Governing Board, 246, 270 Gp120, 246, 266 Gravis, 152, 246 Growth factors, 13, 22, 30, 65, 157, 171, 246, 258 Guanylate Cyclase, 246, 262
H Habitual, 229, 246 Half-Life, 158, 169, 170, 173, 246 Haptens, 216, 246, 273 Headache, 246, 249 Heart attack, 57, 227, 246 Heart failure, 159, 174, 246 Helix-loop-helix, 30, 51, 246 Hemodialysis, 246, 253, 254 Hemodynamics, 91, 102, 246 Hemoglobin, 219, 240, 247, 254 Hemoglobinopathies, 244, 247 Hemolytic, 247, 273 Hemorrhage, 246, 247, 280 Hemostasis, 247, 277 Hepatitis, 86, 243, 247 Hepatobiliary, 17, 247 Hepatocyte, 29, 70, 74, 95, 128, 229, 247 Hepatoma, 136, 247 Heredity, 244, 247 Heterodimer, 51, 247 Heterogeneity, 111, 216, 247 Hexokinase, 10, 247 Hirudin, 160, 247 Histamine, 53, 219, 247 Histidine, 117, 247 Homeobox, 52, 247 Homeostasis, 7, 28, 29, 35, 46, 51, 53, 54, 56, 60, 63, 66, 72, 75, 77, 167, 247 Homodimer, 51, 248 Homologous, 45, 64, 72, 100, 224, 233, 244, 248, 277, 281 Human growth hormone, 19, 155, 248, 278 Humoral, 65, 164, 248 Humour, 248 Hydrocortisone, 140, 248 Hydrogen, 215, 218, 227, 248, 259, 262, 264, 267 Hydrolysis, 35, 222, 224, 229, 248, 252, 255, 266, 269, 272 Hydrophobic, 235, 248, 255 Hydroxylysine, 230, 248 Hydroxyproline, 218, 230, 248 Hypercholesterolemia, 237, 248 Hyperlipidemia, 181, 237, 248 Hyperopia, 57, 248, 274 Hyperplasia, 22, 63, 65, 74, 112, 150, 248 Hypersensitivity, 217, 235, 248, 276 Hypertension, 27, 39, 80, 102, 165, 166, 176, 181, 227, 246, 248, 269, 271, 285 Hyperthermia, 138, 249 Hyperthyroidism, 249, 271
296
Glucagon
Hypertriglyceridemia, 237, 249 Hypertrophy, 233, 248, 249, 284 Hypoglycaemia, 79, 81, 86, 113, 118, 127, 161, 249 Hypoglycemic, 5, 11, 34, 42, 50, 74, 92, 160, 162, 163, 200, 215, 244, 249, 283 Hypoglycemic Agents, 163, 249 Hypoplasia, 150, 249 Hypotension, 233, 249, 262 Hypothalamic, 8, 14, 65, 69, 80, 249 Hypothalamus, 13, 14, 15, 36, 62, 221, 223, 233, 235, 240, 249, 255, 262, 268, 271, 278 Hypothermia, 249 Hypothyroidism, 52, 249 Hypoxic, 10, 249 Hysterosalpingography, 122, 249 I Idiotype, 104, 249 Ileal, 65, 123, 136, 249 Ileum, 65, 168, 172, 228, 249, 253, 262 Imaging procedures, 162, 249, 283 Immune function, 63, 249, 250 Immune response, 151, 216, 220, 222, 246, 249, 250, 280, 287 Immune system, 59, 224, 249, 250, 256, 257, 260, 287 Immunoassay, 19, 233, 249 Immunogenic, 250, 255, 273 Immunoglobulin, 220, 250, 259 Immunohistochemistry, 22, 36, 250 Immunology, 216, 250 Immunomodulator, 250, 255 Immunosuppression, 28, 250, 256 Immunosuppressive, 50, 245, 250 Immunosuppressive Agents, 250 Immunotherapy, 224, 235, 250 Impaction, 81, 105, 121, 250 Impairment, 48, 121, 167, 223, 229, 241, 250 Implant radiation, 250, 252, 253, 273, 287 Implantation, 232, 250 In situ, 13, 36, 39, 71, 101, 250 In Situ Hybridization, 13, 36, 71, 101, 250 In vivo, 23, 24, 25, 26, 28, 29, 31, 32, 34, 38, 41, 43, 44, 56, 59, 73, 82, 83, 88, 112, 113, 133, 138, 142, 158, 169, 170, 173, 244, 250, 257 Incision, 250, 252 Incontinence, 250, 277 Incubation, 16, 250, 266 Incubation period, 250, 266 Induction, 6, 26, 52, 73, 251, 271
Infarction, 127, 134, 251, 274 Infiltration, 63, 251 Inflammation, 63, 217, 220, 227, 230, 240, 241, 243, 244, 247, 248, 251, 265, 269, 275, 276, 280, 281, 282, 284, 285, 286 Inflammatory bowel disease, 86, 175, 251 Infusion, 4, 32, 54, 60, 86, 94, 106, 117, 123, 126, 135, 154, 251 Ingestion, 109, 116, 170, 245, 251, 265, 269, 282 Inhalation, 216, 251, 269 Initiation, 34, 41, 49, 55, 251, 283 Initiator, 34, 251 Inorganic, 52, 251, 256, 260, 268 Inotropic, 134, 237, 251 Insight, 10, 25, 44, 47, 64, 66, 251 Insulator, 251, 260 Insulin-dependent diabetes mellitus, 152, 158, 163, 168, 173, 251 Insulin-like, 22, 55, 56, 63, 65, 251 Interleukin-1, 103, 251 Interleukin-2, 252 Intermittent, 18, 72, 242, 252, 256 Internal radiation, 252, 253, 273, 287 Interstitial, 225, 252, 253, 257, 287 Intestinal Mucosa, 22, 63, 240, 252, 286 Intestine, 53, 58, 62, 115, 150, 153, 156, 162, 170, 175, 224, 225, 252, 254, 266, 273 Intoxication, 252, 287 Intracellular Membranes, 252, 257 Intrahepatic, 39, 50, 252 Intramuscular, 252, 265 Intraocular, 242, 252 Intraocular pressure, 242, 252 Intraperitoneal, 86, 252 Intrinsic, 7, 25, 216, 223, 252 Invasive, 12, 252, 257 Invertebrates, 245, 252, 256 Involuntary, 252, 260, 268, 278, 279 Ion Transport, 65, 136, 252 Ions, 40, 215, 236, 238, 248, 252, 259, 270 Irradiation, 69, 253, 287 Irritable Bowel Syndrome, 169, 253 Ischemia, 60, 63, 219, 222, 243, 253, 274 Isoenzyme, 247, 253 Isozymes, 10, 61, 253, 273 J Jejunum, 65, 131, 253 Jet lag, 180, 253 K Kb, 194, 253 Keratinocyte growth factor, 22, 253
297
Ketoacidosis, 64, 215, 253 Ketone Bodies, 95, 215, 235, 253 Ketosis, 82, 166, 167, 235, 242, 253 Kidney Cortex, 11, 253, 258 Kidney Failure, 46, 159, 174, 239, 253, 254 Kidney Failure, Acute, 253 Kidney Failure, Chronic, 253, 254 Kidney Glomerulus, 253, 254 Kidney Transplantation, 90, 254 Kinetic, 18, 45, 78, 120, 254 L Labile, 231, 254 Lactation, 254, 264, 271 Lag, 254 Laminin, 223, 254 Large Intestine, 150, 158, 175, 228, 236, 252, 254, 274, 278 Lectin, 254, 257 Lens, 57, 135, 254, 287 Leptin, 13, 19, 21, 65, 90, 94, 107, 254 Lesion, 100, 211, 254, 256, 284 Lethal, 17, 71, 242, 254 Lethargy, 249, 254 Leucine, 54, 55, 84, 254 Leukemia, 244, 254 Leukocytes, 225, 229, 254, 260, 262, 284 Life cycle, 224, 254 Ligaments, 233, 254 Ligands, 44, 59, 79, 228, 254 Ligation, 16, 41, 254 Limbic, 14, 218, 255 Limbic System, 218, 255 Linkage, 11, 101, 113, 155, 228, 255 Lipase, 138, 145, 255 Lipid, 65, 71, 126, 132, 133, 168, 170, 181, 221, 245, 251, 255, 260, 284 Lipid A, 65, 255 Lipolysis, 54, 57, 71, 82, 255 Lipopolysaccharide, 14, 66, 255 Lipoprotein, 135, 168, 237, 255, 256 Lithium, 14, 87, 144, 255 Lithium Chloride, 14, 144, 255 Liver Cirrhosis, 116, 255 Liver metastases, 102, 255 Liver Mitochondria, 137, 138, 255 Liver scan, 255, 276 Liver Transplantation, 23, 82, 255 Living Donors, 50, 97, 255 Lobe, 85, 248, 256, 271 Localization, 11, 49, 101, 107, 128, 139, 250, 256
Localized, 11, 57, 233, 238, 251, 254, 256, 268, 284 Longitudinal Studies, 50, 256 Longitudinal study, 126, 256 Long-Term Care, 66, 256 Loop, 48, 56, 123, 256 Low-density lipoprotein, 238, 255, 256 Luciferase, 39, 256 Luminescence, 39, 256 Lupus, 256, 281 Lutein Cells, 256, 271 Lymph, 230, 239, 248, 256, 264, 280 Lymph node, 256, 264 Lymphatic, 239, 251, 256, 258, 279 Lymphocyte, 220, 250, 256, 257 Lymphocyte Depletion, 250, 256 Lymphoid, 220, 257 M Macrophage, 252, 257 Magnetic Resonance Imaging, 47, 257, 276 Malabsorption, 22, 63, 257, 278 Malaise, 14, 257 Malignant, 10, 79, 215, 221, 257, 261, 273 Malignant tumor, 10, 79, 215, 257 Malnutrition, 63, 135, 217, 222, 257 Mammogram, 226, 257, 258 Manic, 255, 257 Mediate, 10, 15, 39, 41, 64, 65, 228, 237, 257 Mediator, 13, 62, 252, 257, 277 Medicament, 164, 176, 257, 281 MEDLINE, 195, 257 Medullary, 81, 257 Meiosis, 224, 257, 281 Melanin, 257, 267, 284 Membrane Fusion, 78, 257 Membrane Proteins, 25, 257 Memory, 9, 72, 79, 219, 257 Meninges, 229, 258 Menopause, 258, 269, 271 Mental, iv, 5, 194, 196, 232, 236, 241, 249, 257, 258, 272, 276, 285 Mental Health, iv, 5, 194, 196, 258, 272 Mesenchymal, 240, 258 Meta-Analysis, 79, 258 Metabolic acidosis, 166, 167, 235, 258 Metabolic disorder, 20, 66, 151, 158, 173, 175, 176, 245, 246, 258 Metabolite, 34, 133, 224, 258 Metallothionein, 38, 258 Metastasis, 213, 228, 258 Metastatic, 100, 258 Methionine, 258, 271
298
Glucagon
MI, 131, 140, 213, 258 Micelle, 93, 258 Microbe, 258, 283 Microbiology, 215, 258 Microcalcifications, 226, 258 Microcirculation, 113, 255, 258 Microglia, 222, 258, 259 Microorganism, 230, 259, 265, 287 Microtubules, 141, 259 Migration, 65, 259 Mitochondria, 7, 10, 41, 57, 259, 263 Mitosis, 221, 259 Mitotic, 259, 286 Mobility, 153, 156, 259 Mobilization, 39, 54, 259 Modeling, 237, 259 Modification, 22, 136, 218, 244, 259, 273 Modulator, 35, 259 Molecular, 10, 11, 17, 20, 24, 26, 32, 34, 35, 36, 40, 42, 44, 46, 48, 49, 51, 54, 55, 56, 58, 61, 63, 64, 80, 83, 85, 87, 94, 95, 96, 100, 107, 110, 111, 150, 157, 171, 195, 197, 224, 232, 237, 243, 258, 259, 271, 274, 283, 284 Molecular Evolution, 96, 259 Molecular Structure, 259, 284 Monitor, 7, 41, 64, 174, 259, 263 Monoamine, 23, 259 Monoclonal, 101, 253, 259, 273, 287 Monoclonal antibodies, 101, 259 Monocytes, 251, 254, 260 Mononuclear, 260, 284 Monophosphate, 71, 136, 260 Monotherapy, 181, 260 Monounsaturated fat, 134, 140, 260 Morphology, 65, 260 Motility, 26, 48, 92, 120, 169, 243, 260, 277 Motion Sickness, 260, 261, 277 Motor Activity, 232, 243, 260 Mucosa, 63, 86, 167, 243, 256, 260, 271, 280 Mucus, 241, 260, 284 Multiple sclerosis, 152, 260 Muscle Fibers, 222, 260, 261 Musculature, 43, 260 Mutagenesis, 64, 260 Mutagens, 260 Myasthenia, 152, 260 Mydriatic, 236, 260, 277 Myelin, 260 Myocardial infarction, 92, 233, 258, 260, 271 Myocardium, 219, 258, 260
Myopia, 57, 260, 261, 274 Myosin, 39, 260 N Natriuresis, 97, 138, 141, 261 Nausea, 108, 169, 243, 253, 261, 285 NCI, 1, 193, 230, 261 Nearsightedness, 260, 261 Necrosis, 221, 251, 258, 260, 261, 274, 275, 277 Needle biopsy, 87, 242, 261 Neonatal, 58, 69, 71, 80, 93, 111, 261 Neoplasia, 261 Neoplasm, 261, 284 Neoplastic, 26, 248, 261 Nephropathy, 11, 261 Nerve Growth Factor, 23, 261 Nervous System, 9, 13, 15, 36, 215, 216, 217, 223, 229, 243, 245, 246, 257, 259, 260, 261, 262, 263, 266, 277, 281 Neural, 12, 32, 51, 112, 128, 216, 218, 248, 258, 261, 266 Neuroanatomy, 36, 255, 261 Neuroendocrine, 8, 17, 25, 56, 60, 61, 62, 66, 140, 261 Neuroendocrinology, 36, 261 Neuronal, 8, 23, 36, 45, 47, 49, 53, 261 Neurons, 8, 13, 14, 15, 23, 27, 36, 62, 65, 235, 241, 243, 261, 262, 281 Neuropathy, 217, 261 Neuropeptide, 8, 27, 36, 60, 61, 62, 65, 233, 262 Neurophysiology, 235, 262 Neurosecretory Systems, 239, 262 Neurotensin, 26, 63, 262 Neurotoxicity, 9, 262 Neurotoxin, 83, 262 Neurotransmitter, 8, 215, 216, 218, 222, 225, 226, 237, 243, 245, 247, 262, 278, 280, 286 Neutralization, 48, 74, 262 Neutrons, 253, 262, 273 Neutrophils, 243, 254, 262 Nifedipine, 123, 262 Nitric Oxide, 29, 39, 262 Nitrogen, 48, 217, 218, 245, 254, 262, 284 Norepinephrine, 12, 24, 216, 237, 262 Normotensive, 102, 263 Nuclear, 23, 34, 47, 51, 64, 94, 122, 238, 241, 255, 261, 263, 285 Nuclei, 218, 238, 244, 255, 257, 259, 262, 263 Nucleic acid, 250, 260, 262, 263, 273, 276
299
Nucleus, 14, 36, 49, 62, 65, 221, 223, 229, 234, 241, 257, 260, 262, 263, 271 Nutritional Status, 56, 263 Nutritional Support, 48, 58, 263 O Oligomenorrhea, 263, 269 Oligopeptides, 164, 263 Oliguria, 253, 254, 263 Oocytes, 40, 263 Opacity, 235, 263 Operon, 263, 275 Opsin, 263, 275, 276 Optic Chiasm, 249, 263 Optic Nerve, 263, 275, 276 Organelles, 41, 230, 234, 260, 263, 268 Organogenesis, 12, 264 Osmotic, 217, 264, 278 Osteoclasts, 226, 264 Osteoporosis, 166, 167, 264 Ovaries, 264, 269, 275 Ovary, 233, 240, 264 Overdose, 121, 123, 243, 264 Overexpress, 11, 264 Ovum, 233, 234, 244, 254, 264, 270, 271, 287, 288 Oxidation, 25, 32, 33, 48, 57, 84, 137, 215, 224, 234, 235, 264 Oxygen Consumption, 264, 275 Oxytocin, 62, 264 P Palliative, 264, 282 Pancreas Transplant, 50, 51, 264 Pancreas Transplantation, 50, 51, 264 Pancreatectomy, 50, 109, 264 Pancreatic cancer, 40, 51, 265 Pancreatic Hormones, 17, 30, 42, 265 Pancreatic Polypeptide, 12, 19, 21, 25, 52, 79, 96, 106, 118, 119, 265 Pancreatitis, 51, 63, 112, 121, 265 Paradoxical, 115, 265 Parathyroid, 11, 84, 87, 265, 282 Parathyroid Glands, 265 Parathyroid hormone, 11, 87, 265 Parenteral, 22, 33, 48, 58, 63, 65, 83, 132, 172, 181, 239, 265 Parenteral Nutrition, 22, 33, 48, 58, 63, 65, 132, 181, 265 Paroxysmal, 115, 219, 265, 266, 287 Particle, 142, 258, 265, 279, 283 Parturition, 265, 271 Patch, 24, 39, 265 Pathogen, 250, 265
Pathogenesis, 6, 27, 42, 45, 168, 265 Pathologic, 60, 215, 221, 224, 233, 248, 265, 286 Pathologic Processes, 221, 265 Pathologies, 8, 152, 265 Pathophysiology, 11, 61, 64, 99, 266 Patient Education, 200, 201, 206, 208, 213, 266 Penicillamine, 127, 266 Penicillin, 220, 266, 285 Penis, 266, 275 Pepsin, 266, 277 Peptide, 7, 8, 9, 13, 14, 15, 17, 19, 20, 21, 22, 24, 26, 27, 28, 30, 36, 37, 38, 41, 58, 59, 61, 62, 63, 64, 65, 66, 69, 72, 74, 78, 79, 80, 81, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 95, 96, 97, 98, 99, 100, 101, 102, 104, 105, 106, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 127, 131, 133, 134, 136, 137, 138, 139, 140, 142, 144, 150, 153, 154, 155, 156, 157, 158, 160, 162, 163, 164, 165, 166, 167, 169, 170, 171, 172, 173, 175, 218, 226, 233, 239, 254, 265, 266, 269, 271, 272, 282 Peptide Fragments, 153, 266 Peptide Library, 155, 266 Peptide T, 133, 170, 266 Perinatal, 11, 266 Periodicity, 37, 266 Peripheral Nervous System, 262, 266, 278, 280, 286 Peristalsis, 86, 266 Peritoneal, 252, 266 Peritoneal Cavity, 252, 266 Pertussis, 136, 266, 287 PH, 7, 39, 67, 68, 71, 267 Pharmaceutical Preparations, 229, 241, 244, 267 Pharmacodynamics, 115, 267 Pharmacokinetic, 267 Pharmacologic, 6, 18, 27, 219, 246, 267, 283 Phenotype, 10, 17, 45, 52, 267 Phenylalanine, 267, 284 Phosphodiesterase, 54, 267 Phosphodiesterase Inhibitors, 54, 267 Phospholipids, 241, 255, 267 Phosphorus, 226, 265, 267, 268 Phosphorylase, 49, 139, 166, 267, 268 Phosphorylase a, 49, 267, 268 Phosphorylase b, 267, 268 Phosphorylase Phosphatase, 139, 267, 268
300
Glucagon
Phosphorylated, 48, 61, 221, 267, 268 Phosphorylation, 16, 34, 48, 56, 61, 267, 268, 272, 273 Phototransduction, 221, 268 Physical Examination, 229, 268 Physiologic, 16, 33, 41, 42, 63, 71, 73, 109, 217, 224, 246, 268, 274 Pigments, 227, 268, 275 Piloerection, 249, 268 Pituitary Gland, 179, 233, 242, 268, 271, 277 Placenta, 60, 240, 268, 270 Plants, 217, 222, 226, 227, 245, 254, 260, 263, 268, 283 Plasma cells, 220, 268 Plasma protein, 217, 268, 278 Plastids, 264, 268 Platelet Aggregation, 219, 242, 262, 268 Platelets, 262, 268, 282 Platinum, 256, 269 Pneumonia, 232, 269 Poisoning, 100, 226, 243, 252, 255, 261, 269 Polycystic, 114, 269 Polycystic Ovary Syndrome, 114, 269 Polyethylene, 155, 269 Polymerase, 269, 275 Polymers, 155, 269, 272 Polymorphic, 101, 269 Polymorphism, 69, 80, 99, 101, 105, 269 Polysaccharide, 220, 229, 269, 272 Polyuria, 151, 269 Portal Hypertension, 99, 113, 269 Portal Pressure, 39, 269 Portosystemic Shunt, 39, 269 Posterior, 179, 219, 229, 237, 264, 269, 276 Postmenopausal, 264, 269 Postnatal, 14, 76, 269, 279 Postoperative, 169, 269 Postprandial, 4, 94, 95, 100, 103, 107, 109, 113, 118, 134, 164, 270 Postsynaptic, 14, 270 Post-translational, 30, 59, 160, 164, 270 Potassium, 24, 73, 136, 152, 217, 270 Potassium Channels, 24, 136, 270 Potentiates, 9, 252, 270 Potentiating, 108, 176, 270 Potentiation, 50, 270 Practice Guidelines, 196, 270 Precursor, 10, 33, 52, 60, 64, 76, 150, 157, 160, 164, 171, 221, 237, 238, 240, 262, 267, 270, 271, 284, 285 Premedication, 118, 169, 270, 277
Presumptive, 42, 270 Presynaptic, 83, 262, 270 Prevalence, 11, 27, 30, 154, 270 Problem Solving, 181, 270 Progesterone, 12, 270, 271, 280 Progression, 25, 41, 58, 98, 163, 166, 219, 270 Progressive, 16, 30, 228, 229, 230, 237, 254, 261, 270, 284 Proinsulin, 9, 19, 20, 21, 60, 61, 132, 233, 270, 272 Projection, 262, 263, 271 Prolactin, 12, 141, 271 Proline, 230, 248, 271 Promoter, 10, 38, 42, 50, 53, 56, 68, 137, 271 Pro-Opiomelanocortin, 36, 271 Prophase, 224, 263, 271, 281 Propranolol, 82, 271 Prospective study, 256, 271 Prostaglandins, 26, 66, 221, 271 Prostate, 271, 275 Protease, 141, 271 Protease Inhibitors, 141, 271 Protein Binding, 51, 100, 271 Protein C, 25, 34, 133, 217, 218, 221, 223, 230, 255, 271, 285 Protein Conformation, 218, 271 Protein Kinases, 10, 26, 39, 48, 272 Protein S, 23, 25, 54, 55, 116, 123, 182, 224, 248, 272, 276 Proteins, 11, 17, 30, 34, 39, 48, 50, 55, 58, 61, 68, 77, 128, 144, 151, 152, 154, 160, 161, 169, 170, 218, 220, 221, 222, 227, 228, 229, 230, 231, 234, 247, 248, 252, 257, 259, 262, 266, 268, 269, 271, 272, 274, 276, 277, 282, 283, 285 Protein-Tyrosine Kinase, 244, 272 Proteoglycans, 223, 272 Proteolytic, 17, 158, 172, 173, 218, 231, 272 Protocol, 29, 32, 272 Psychic, 258, 272, 277 Psychoactive, 272, 287 Psychogenic, 8, 272 Public Health, 157, 196, 272 Public Policy, 195, 272 Publishing, 67, 183, 200, 201, 272 Pulmonary, 225, 226, 233, 253, 272, 275, 286 Pulmonary Artery, 225, 272, 286 Pulmonary Edema, 253, 272 Pulmonary hypertension, 233, 272 Pulse, 37, 259, 272
301
Purified Insulins, 271, 272 Purines, 272, 277 Pylorus, 237, 273 Pyrimidines, 273, 277 Pyruvate Kinase, 38, 273 Q Quality of Life, 25, 58, 62, 273 Quaternary, 40, 271, 273, 277 R Race, 259, 273 Radiation, 219, 234, 241, 242, 249, 250, 252, 253, 273, 276, 287 Radiation therapy, 241, 242, 252, 253, 273, 287 Radioactive, 20, 225, 246, 248, 250, 252, 253, 255, 259, 263, 273, 276, 281, 285, 287 Radioimmunoassay, 20, 21, 133, 135, 136, 273 Radioisotope, 273, 283 Radiolabeled, 19, 253, 273, 287 Radiology, 81, 87, 100, 122, 162, 273 Radiotherapy, 225, 253, 273, 287 Randomized, 22, 31, 238, 273 Reactivation, 44, 273 Reactive Oxygen Species, 41, 274 Reagent, 256, 274 Receptor, 8, 9, 13, 15, 16, 25, 31, 39, 44, 48, 49, 59, 61, 62, 64, 65, 68, 69, 71, 72, 73, 74, 77, 78, 79, 80, 85, 88, 89, 91, 92, 93, 96, 98, 99, 101, 102, 104, 105, 107, 110, 111, 113, 117, 118, 119, 120, 121, 128, 131, 134, 135, 137, 140, 155, 164, 165, 166, 168, 170, 175, 176, 215, 220, 237, 246, 266, 273, 274, 277 Receptors, Serotonin, 274, 277 Recombinant, 22, 154, 274, 286 Recombination, 45, 64, 244, 274 Rectum, 221, 223, 225, 231, 236, 242, 243, 250, 251, 254, 271, 274, 281 Recur, 266, 274 Recurrence, 266, 274 Red blood cells, 94, 240, 247, 274 Reductase, 217, 274 Refer, 1, 152, 226, 231, 256, 262, 274, 283 Refraction, 260, 274, 279 Refractive Power, 260, 274 Regeneration, 52, 58, 63, 94, 274 Regimen, 4, 165, 238, 274 Relaxant, 242, 274 Reliability, 162, 274 Renal Circulation, 225, 274 Renal tubular, 40, 274
Reperfusion, 92, 274, 275 Reperfusion Injury, 274, 275 Repressor, 51, 263, 275 Reproductive system, 180, 275 Resection, 22, 62, 63, 65, 107, 275, 278 Respiration, 136, 227, 259, 275 Respiratory System, 275, 286 Respiratory Therapy, 32, 275 Restitution, 63, 275 Resuscitation, 238, 275 Retina, 57, 229, 232, 254, 260, 263, 268, 275, 276, 285, 287 Retinal, 135, 221, 263, 268, 275, 276 Retinol, 275, 276 Retinopathy, 217, 275 Retrograde, 13, 275 Retroviral vector, 244, 275 Rheumatism, 276 Rheumatoid, 152, 231, 276 Rheumatoid arthritis, 152, 231, 276 Rhodopsin, 221, 263, 275, 276 Ribonucleic acid, 75, 85, 276 Ribose, 216, 276 Ribosome, 276, 284 Risk factor, 6, 27, 271, 276 Rod, 230, 276 S Saliva, 276 Salivary, 21, 140, 141, 236, 265, 276, 280 Salivary glands, 140, 236, 276 Satiation, 49, 276 Scans, 100, 276 Schizoid, 276, 287 Schizophrenia, 276, 287 Schizotypal Personality Disorder, 276, 287 Sclera, 229, 276, 285 Sclerosis, 231, 260, 277 Scopolamine, 86, 118, 277 Screening, 25, 31, 123, 154, 155, 230, 277 Secretin, 48, 76, 82, 84, 104, 123, 147, 153, 156, 167, 277 Secretory, 9, 17, 18, 20, 24, 31, 37, 43, 50, 53, 89, 102, 114, 115, 132, 153, 154, 156, 233, 277 Secretory Vesicles, 9, 277 Segregation, 11, 12, 274, 277 Seizures, 132, 265, 277 Sella Turcica, 237, 268, 277 Senile, 264, 277 Sensor, 9, 277 Sepsis, 29, 52, 258, 277 Septic, 52, 277
302
Glucagon
Sequence Homology, 170, 266, 277 Sequester, 41, 277 Serine, 102, 239, 267, 277 Serotonin, 13, 262, 274, 277, 284 Serum Albumin, 273, 278 Shock, 162, 248, 278, 284 Short Bowel Syndrome, 22, 63, 65, 99, 278 Side effect, 154, 169, 175, 181, 189, 216, 224, 278, 283 Skeletal, 31, 54, 55, 60, 230, 278, 279 Skeleton, 215, 278 Skull, 278, 282 Small intestine, 51, 58, 150, 175, 228, 230, 234, 237, 248, 249, 252, 253, 278 Smooth muscle, 39, 162, 217, 219, 225, 242, 247, 278, 279, 280 Sneezing, 266, 278 Social Environment, 273, 278 Sodium, 73, 80, 138, 217, 246, 261, 268, 278, 281 Soft tissue, 225, 278 Solvent, 215, 223, 241, 245, 264, 278 Somatic, 238, 248, 255, 257, 259, 264, 266, 278, 285 Sorbitol, 217, 247, 278 Sound wave, 232, 279 Spasm, 81, 221, 279, 282 Spasmodic, 267, 279 Spasmolytic, 162, 279 Spastic, 253, 279 Specialist, 202, 236, 279 Specificity, 18, 28, 59, 60, 121, 143, 216, 239, 279 Spectroscopic, 59, 279 Spectrum, 31, 258, 279 Sperm, 229, 279, 284 Spinal cord, 13, 222, 229, 240, 258, 261, 266, 279, 281 Spleen, 256, 264, 279 Staging, 276, 279 Standardize, 18, 279 Steady state, 32, 165, 279 Steel, 230, 279 Stem Cells, 18, 40, 52, 64, 279 Sterile, 265, 279 Steroid, 223, 233, 279 Stimulant, 153, 156, 247, 280, 285 Stimulus, 150, 158, 232, 237, 241, 254, 280, 282 Stomatitis, 244, 280 Stool, 231, 250, 253, 254, 280 Streptozocin, 11, 280
Stress, 8, 14, 27, 29, 60, 132, 134, 140, 201, 223, 227, 233, 243, 253, 261, 276, 280 Stria, 14, 280 Stroke, 27, 57, 194, 227, 280 Subacute, 251, 280 Subclinical, 251, 277, 280 Subcutaneous, 3, 4, 80, 91, 106, 112, 116, 119, 126, 216, 265, 280 Submaxillary, 240, 280 Subspecies, 279, 280 Substance P, 258, 277, 280 Substrate, 25, 29, 32, 33, 44, 60, 280 Substrate Specificity, 60, 280 Suction, 242, 280 Superior Cervical Ganglion, 127, 280 Supplementation, 43, 176, 280 Suppositories, 244, 281 Suppression, 6, 24, 33, 66, 71, 72, 75, 94, 103, 107, 151, 155, 165, 171, 281 Suppressive, 68, 281 Supraventricular, 115, 281 Suspensions, 161, 281, 285 Sweat, 249, 281 Sympathetic Nervous System, 12, 223, 281 Sympathomimetic, 237, 240, 263, 281 Symptomatic, 119, 121, 220, 265, 281 Synapse, 216, 270, 281, 284 Synaptic, 50, 262, 281 Synergistic, 271, 281 Systemic, 14, 23, 36, 123, 152, 190, 225, 231, 240, 246, 251, 253, 273, 280, 281, 284, 287 Systemic lupus erythematosus, 152, 231, 281 Systolic, 248, 281 T Tachycardia, 115, 281 Technetium, 94, 281 Temporal, 30, 57, 61, 67, 218, 282 Temporal Lobe, 218, 282 Teratogenic, 236, 282 Terminalis, 14, 282 Testis, 60, 240, 282 Tetany, 265, 282 Therapeutics, 39, 98, 99, 118, 137, 190, 282 Threonine, 266, 277, 282 Threshold, 6, 165, 248, 282 Thrombin, 268, 271, 282 Thrombocytopenia, 86, 282 Thrombomodulin, 271, 282 Thrombosis, 272, 280, 282 Thrombus, 233, 251, 268, 282
303
Thyroid, 10, 52, 65, 142, 179, 226, 249, 265, 282, 284 Thyroid Gland, 179, 249, 265, 282 Thyroid Hormones, 282, 284 Thyroiditis, 152, 282 Thyrotropin, 10, 65, 106, 249, 282 Thyroxine, 217, 267, 282 Tolazamide, 183, 283 Tolerance, 27, 30, 43, 51, 90, 95, 103, 115, 116, 127, 140, 154, 166, 167, 172, 176, 212, 215, 242, 245, 283 Tone, 263, 283 Tonic, 45, 49, 283 Tooth Preparation, 215, 283 Torsion, 251, 283 Total pancreatectomy, 115, 264, 283 Toxic, iv, 50, 222, 223, 262, 283 Toxicity, 81, 122, 140, 158, 173, 237, 283 Toxicokinetics, 283 Toxicology, 39, 96, 108, 196, 283 Toxin, 136, 239, 283 Tracer, 15, 19, 32, 49, 54, 141, 283 Trachea, 226, 241, 282, 283 Traction, 230, 283 Tractus, 49, 66, 283 Transcription Factors, 30, 42, 44, 46, 51, 283 Transduction, 26, 29, 39, 48, 54, 59, 63, 64, 93, 170, 283 Transfection, 11, 23, 144, 224, 244, 283 Transgenes, 47, 283 Translation, 54, 55, 218, 283 Translational, 55, 60, 284 Transmitter, 215, 222, 237, 257, 262, 284 Transplantation, 7, 23, 28, 50, 51, 82, 90, 104, 154, 200, 229, 257, 284 Trauma, 246, 261, 265, 284 Tricuspid Atresia, 233, 284 Tricyclic, 100, 121, 284 Triglyceride, 4, 57, 103, 111, 135, 249, 284 Trophic, 26, 58, 150, 284 Tryptophan, 230, 277, 284 Tubulin, 259, 284 Tumor Necrosis Factor, 103, 284 Tumour, 79, 284 Tunica, 260, 284 Tyrosine, 166, 237, 272, 284 U Ulcer, 111, 237, 284 Ulcerative colitis, 99, 251, 284 Unconscious, 201, 219, 284 Uraemia, 265, 284
Uranium, 281, 285 Urea, 121, 254, 281, 284, 285 Uremia, 72, 253, 285 Ureters, 285 Urethra, 266, 271, 285 Urinary, 95, 102, 122, 180, 250, 263, 269, 277, 285 Urinary tract, 180, 285 Urine, 40, 71, 151, 224, 236, 240, 250, 253, 254, 261, 263, 269, 285 Uterine Contraction, 264, 285 Uterus, 229, 233, 234, 249, 262, 264, 270, 275, 285 Uveitis, 221, 285 V Vaccines, 285, 287 Vacuoles, 264, 285 Vagal, 14, 49, 56, 62, 92, 123, 285 Vagina, 229, 235, 275, 285 Vaginal, 180, 285 Vagus Nerve, 285 Valine, 266, 285 Vascular, 39, 78, 151, 217, 224, 225, 229, 239, 251, 255, 258, 262, 268, 282, 285 Vasculitis, 265, 286 Vasoactive, 48, 110, 141, 153, 156, 286 Vasoactive Intestinal Peptide, 153, 156, 286 Vasoconstriction, 240, 286 Vasodilation, 39, 286 Vasodilator, 225, 237, 247, 262, 286 Vector, 283, 286 Vein, 24, 99, 219, 221, 252, 263, 269, 286 Venom, 170, 286 Venous, 49, 221, 269, 272, 284, 286 Venous Pressure, 269, 286 Ventral, 221, 249, 286 Ventricle, 218, 221, 222, 233, 249, 272, 281, 284, 286 Ventricular, 92, 132, 233, 284, 286 Ventricular Dysfunction, 92, 286 Venules, 225, 226, 258, 286 Vertebrae, 279, 286 Vesicular, 23, 53, 286 Veterinary Medicine, 195, 286 Vial, 4, 187, 286 Vinblastine, 139, 142, 284, 286 Vinca Alkaloids, 286 Viral, 23, 283, 286 Virulence, 222, 283, 286 Virus, 14, 38, 136, 223, 240, 244, 246, 275, 283, 286, 287
304
Glucagon
Visceral, 14, 15, 144, 223, 255, 285, 287 Viscosity, 225, 287 Vitreous, 254, 275, 287 Vitreous Body, 275, 287 Vitro, 24, 26, 29, 34, 39, 41, 45, 56, 59, 60, 66, 67, 70, 78, 82, 83, 102, 113, 131, 133, 139, 140, 157, 225, 244, 250, 287 W White blood cell, 220, 254, 256, 257, 260, 268, 287 Whooping Cough, 267, 287 Windpipe, 282, 287 Withdrawal, 41, 287
Womb, 275, 285, 287 Wound Healing, 228, 287 X Xenograft, 219, 287 X-ray, 26, 223, 228, 232, 242, 253, 257, 263, 273, 276, 287 X-ray therapy, 253, 287 Y Yeasts, 160, 267, 287 Z Zygote, 232, 288 Zymogen, 271, 288